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Sample records for creatine kinase neuron

  1. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

  2. Oxidized Form of Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    王希成; 王帆; 邹晓明; 周海梦

    1994-01-01

    The purified rabbit muscle creatine kinase (R-CK) was previously considered homogeneousand without disulfide bonds.By the method of NR/R two-dimensional diagonal SDS-PAGE,two forms of R-CK,designated respectively "oxidized form" of creatine kinase which contained intrachain disulfide bondsand "reduced form" of creatine kinase which did not have any —S—S— bridges,were for the first time sepa-rated.They were found to be the same in amino acid composition,in subunit molecular Weight and in isoelec-tric point,and were almost identical in enzyme activities.Thus it is hard to isolate one from the other bycommon biochemical methods.More extensive studies show that the oxidized form of CK also contains a pair of reactive thiol groupswhich are essential to the enzyme activity,and it has one intrachain disulfide bond per subunit.In the nativestate,this —S—S— bond cannot be reduced by DTT,but by treating the reduced form of CK with some ox-idants,these —S—S— bonds can be formed in vitro.Thus it is presumed that the disulfide bonds are cross-linked through the oxidization of two shallowly buried —SH groups.

  3. Creatine supplementation: effects on blood creatine kinase activity responses to resistance exercise and creatine kinase activity measurement

    National Research Council Canada - National Science Library

    Marco Machado; Rafael Pereira; Felipe Sampaio-Jorge; Franz Knifis; Anthony Hackney

    2009-01-01

    The purpose of this study was to determine the effects of creatine supplementation and exercise on the integrity of muscle fiber, as well as the effect of the supplementation on the creatine kinase (CK) assay measurement...

  4. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy.......Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...

  5. 21 CFR 862.1215 - Creatine phosphokinase/creatine kinase or isoenzymes test system.

    Science.gov (United States)

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test...

  6. Macro creatine kinase type 1: a cause of spuriously elevated serum creatine kinase associated with leukoencephalopathy in a child.

    Science.gov (United States)

    Bodensteiner, John B

    2014-07-01

    Macro creatine kinase type 1 is a complex formed by the creatine kinase isoenzyme BB and monoclonal IgG and occurs in about 1% of patients studied. First identified as a cause of spurious elevation of the total serum creatine kinase in patients suspected of myocardial infarction, the test has been largely replaced by the measurement of troponin levels. We present a child with delayed milestones and persistently elevated total serum creatine kinase measurements (∼ 1000-4000 IU) normal electromyogram and brisk myotatic reflexes. Creatine kinase isoenzymes and brain imaging showed the presence of macro creatine kinase type 1 and extensive signal abnormality of the cerebral white matter. Macro creatine kinase type 1 has been associated with several conditions though it has not been described in association with leukoencephalopathy or in patients this young. Macro creatine kinase type 1 can be a cause of elevated total creatine kinase in patients without primary muscle disease. The significance of the relationship of the macro creatine kinase to the leukoencephalopathy in this patient is unknown.

  7. Creatine kinase activity is associated with blood pressure.

    Science.gov (United States)

    Brewster, Lizzy M; Mairuhu, Gideon; Bindraban, Navin R; Koopmans, Richard P; Clark, Joseph F; van Montfrans, Gert A

    2006-11-07

    We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular contraction, and antagonizes nitric oxide-mediated functions. Relatively high activity of the enzyme, particularly in resistance arteries, is thought to enhance pressor responses and increase blood pressure. Tissue creatine kinase activity is reported to be high in black people, a population subgroup with greater hypertension risk; the proposed effects of high creatine kinase activity, however, are not "race dependent." We therefore assessed whether creatine kinase is associated with blood pressure in a multiethnic population. We analyzed a stratified random sample of the population of Amsterdam, The Netherlands, consisting of 1444 citizens (503 white European, 292 South Asian, 580 black, and 69 of other ethnicity) aged 34 to 60 years. We used linear regression analysis to investigate the association between blood pressure and normal serum creatine kinase after rest, as a substitute measure of tissue activity. Creatine kinase was independently associated with blood pressure, with an increase in systolic and diastolic pressure, respectively, of 8.0 (95% CI, 3.3 to 12.7) and 4.7 (95% CI, 1.9 to 7.5) mm Hg per log creatine kinase increase after adjustment for age, sex, body mass index, and ethnicity. Creatine kinase is associated with blood pressure. Further studies are needed to explore the nature of this association, including how variation in cardiovascular creatine kinase activity may affect pressor responses.

  8. Creatine kinase and creatine kinase subunit-B in coronary sinus blood in pacing-induced angina pectoris

    DEFF Research Database (Denmark)

    Bagger, J P; Ingerslev, J; Heinsvig, E M

    1982-01-01

    In nine out of 10 patients with angiographic documented coronary artery disease, pacing-induced angina pectoris provoked myocardial production of lactate, whereas no significant release of either creatine kinase or creatine kinase subunit-B to coronary sinus and peripheral venous blood could...

  9. Creatine-creatine phosphate shuttle modeled as two-compartment system at different levels of creatine kinase activity

    DEFF Research Database (Denmark)

    Fedosov, Sergey

    1994-01-01

    In order to characterize ADP-ATP and creatine-creatine phosphate (Cr-CrP) shuttles a minimal mathematical model with two compartments and cyclic turnover of matter was designed. The 'mitochondrial' compartment contained 'ATP-synthase' and 'mitochondrial ereatine kinase' (mitCK). The 'cytoplasmic......' compartment consisted of 'ATPase', 'cytoplasmic creatine kinase' (cytCK) and an 'ADP-binding structure'. The exchange of metabolites between these compartments was limited. Different levels of cytCK and mitCK expression as welt as different exchange rate constants between the compartments were assigned...

  10. Creatine supplementation: exploring the role of the creatine kinase/phosphocreatine system in human muscle.

    Science.gov (United States)

    Hespel, P; Eijnde, B O; Derave, W; Richter, E A

    2001-01-01

    The effect of oral creatine supplementation on high-intensity exercise performance has been extensively studied over the past ten years and its ergogenic potential in young healthy subjects is now well documented. Recently, research has shifted from performance evaluation towards elucidating the mechanisms underlying enhanced muscle functional capacity after creatine supplementation. In this review, we attempt to summarise recent advances in the understanding of potential mechanisms of action of creatine supplementation at the level of skeletal muscle cells. By increasing intracellular creatine content, oral creatine ingestion conceivably stimulates operation of the creatine kinase (CK)/phosphocreatine (PCr) system, which in turn facilitates muscle relaxation. Furthermore, evidence is accumulating to suggest that creatine supplementation can beneficially impact on muscle protein and glycogen synthesis. Thus, muscle hypertrophy and glycogen supercompensation are candidate factors to explain the ergogenic potential of creatine ingestion. Additional issues discussed in this review are the fibre-type specificity of muscle creatine metabolism, the identification of responders versus non-responders to creatine intake, and the scientific background concerning potential side effects of creatine supplementation.

  11. Proteolytic susceptibility of creatine kinase isozymes and arginine kinase.

    Science.gov (United States)

    Ercan, Altan; Grossman, Steven H

    2003-07-11

    The time course and dose-response to proteolysis of three dimeric isozymes of creatine kinase, CK-MM (muscle), CK-BB (brain), and CK-MB (heart) and the homologous monomer, arginine kinase were compared. Chymotrypsin and trypsin cause a rapid and significant loss of intact CK-BB, but limited hydrolysis of CK-MM. After 1h of hydrolysis by chymotrypsin, 80% of CK-MM is intact as judged by quantification of monomers after electrophoresis in sodium dodecyl sulfate. While 50% of the intact monomers of CK-MB remain under these conditions, no CK-BB monomers are detected. These results indicate that treatment with chymotrypsin leads to a CK-MB devoid of the B-subunit. When treated with trypsin for 1h, CK-MM is totally resistant to hydrolysis and all CK-BB is highly degraded. However, CK-MB exhibits approximately 90% intact monomers, indicating survival of intact B-subunit in CK-MB. This suggests that heterodimerization of a B-subunit with an M-subunit may have a protective effect against hydrolysis by trypsin. In view of the considerably larger number of potentially tryptic sensitive sites on the muscle isozyme, the resistance of CK-MM and susceptibility of CK-BB dimers to trypsin implies that differences in subunit tertiary structure are a factor in proteolysis of the homodimeric isozymes. Arginine kinase is rapidly degraded by trypsin, but is minimally affected by chymotrypsin. The finding that both a monomeric (arginine kinase) and dimeric (CK-BB) phosphagen kinase are highly susceptible to proteolysis by trypsin indicates that quaternary structure is not, in and of itself, an advantage in resistance to proteolysis. Since both arginine kinase and muscle creatine kinase are resistant to chymotryptic hydrolysis, it seems unlikely that in general, the increased packing density, which may result from dimerization can account for the stability of CK-MM towards trypsin.

  12. The creatine kinase response to resistance exercise.

    Science.gov (United States)

    Koch, A J; Pereira, R; Machado, M

    2014-03-01

    Resistance exercise can result in localized damage to muscle tissue. This damage may be observed in sarcolemma, basal lamina, as well as, in the contractile elements and the cytoskeleton. Usually the damage is accompanied by release of enzymes such as creatine kinase (CK) and lactate dehydrogenase, myoglobin and other proteins into the blood. Serum CK has been proposed as one of the best indirect indicators of muscle damage due to its ease of identification and the relatively low cost of assays to quantify it. Thus, CK has been used as an indicator of the training intensity and a diagnostic marker of overtraining. However, some issues complicate CK's use in this manner. There is great interindividual variability in serum CK, which complicates the assignment of reliable reference values for athletes. Furthermore, factors such as training level, muscle groups involved, and gender can influence CK levels to a greater extent than differences in exercise volume completed. This review will detail the process by which resistance exercise induces a rise in circulating CK, illuminate the various factors that affect the CK response to resistance exercise, and discuss the relative usefulness of CK as a marker of training status, in light of these factors.

  13. Macro-creatine kinase: a neglected cause of elevated creatine kinase.

    Science.gov (United States)

    Aljuani, F; Tournadre, A; Cecchetti, S; Soubrier, M; Dubost, J J

    2015-04-01

    Macro-creatine kinase (macro-CK) is a neglected cause of raised CK. Over a 10-year period, we observed five cases. Three patients had macro-CK type 1. One patient with fibromyalgia underwent several explorations to find a muscular pathology; another, who had elevated CK-MB (muscle-brain fraction) activity, was referred to a cardiologist, and statin therapy was erroneously discontinued in two patients. Two patients had macro-CK type 2: a man with a neuroendocrine carcinoma and a woman with rheumatoid arthritis. Diagnosis of type 1 obviates the need to carry out pointless and expensive investigations seeking a neuromuscular or cardiac pathology, and also, the unwarranted discontinuation of statin therapy. Type 2 must prompt investigations for a neoplasm.

  14. EVALUATION OF SERUM CREATINE KINASE LEVELS IN PATIENTS WITH HYPOTHYROIDISM

    Directory of Open Access Journals (Sweden)

    Rekha Nanjundasetty

    2016-05-01

    Full Text Available BACKGROUND Thyroid disorders are common endocrine disorders. Thyroid function tests which are usually done are measurement of blood levels of hormones Triiodothyronine (T3, Thyroxine (T4 and Thyroid Stimulating Hormone (TSH, which are affected by various nonspecific conditions. Therefore, the present study is done to evaluate the role of additional biochemical parameter Creatine Kinase (CK in diagnosing hypothyroidism. Thyroid function and Creatine Kinase activity was measured in 70 patients with clinically suspected cases of hypothyroidism. Patients with hypothyroidism will have decreased T3, T4 levels and increased levels of TSH. However, whether there is any correlation of Creatine Kinase with hypothyroidism is not well established. In our study, we found that in hypothyroid patients there is significant increase in CK levels. Measurement of CK levels is an additional biochemical parameter to diagnose hypothyroidism

  15. Creatine supplementation: effects on blood creatine kinase activity responses to resistance exercise and creatine kinase activity measurement

    Directory of Open Access Journals (Sweden)

    Marco Machado

    2009-12-01

    Full Text Available The purpose of this study was to determine the effects of creatine supplementation and exercise on the integrity of muscle fiber, as well as the effect of the supplementation on the creatine kinase (CK assay measurement. Forty-nine sedentary individuals participated in a double-blind study and were divided into two groups: C (n=26 received 4x5-day packages of 0.6 g.kg-1 of body weight contained 50% of creatine + 50% of dextrose, and P (n=23 received packages containing only dextrose. On the first day the groups performed a 1RM test for bench press, seated row, leg extension, leg curl and leg press. On D7 they received the supplements. On the fourteenth day, they performed a training session of five exercises, each in three sets of ten repetitions at 75% of 1RM. Blood was collected before (D14 and after the exercise session (D15. Differing levels of blood creatine were tested to determine the influence on the assay measurements of CK. ANOVA and Tukey's post-hoc tests were used to compare groups and different times of study protocol (PO objetivo do presente estudo foi determinar o efeito da suplementação de creatina e do exercício na integridade das fibras musculares e, também, o efeito da suplementação na técnica de mensuração da atividade da creatina kinase (CK. Quarenta e nove sedentários participaram de um estudo duplo-cego e foram divididos em dois grupos: C (n=26 que receberam 4x5 dias embalagens com 0,6 g.kg-1 de massa corporal com 50% de creatina + 50% de dextrose, e P (n=23 que receberam embalagens contendo apenas dextrose. No primeiro dia, eles realizaram o teste de 1RM para os exercícios supino reto, remada sentada, cadeira extensora, mesa flexora, e leg press. No D7 receberam os suplementos. No décimo quarto dia eles realizaram uma sessão de treinos com os cinco exercícios, cada um com 3x10 repetições a 75% de 1RM. Sangue foi coletado antes (D14 e depois da sessão de exercícios (D15. Diferentes concentrações de

  16. Creatine kinase MB isoenzyme in dermatomyositis: a noncardiac source

    Energy Technology Data Exchange (ETDEWEB)

    Larca, L.J.; Coppola, J.T.; Honig, S.

    1981-03-01

    Three patients with polymyositis had elevated serum levels of creatine kinase MB isoenzyme. The presence of this isoenzyme is used extensively to diagnose myocardial infarction, but the isoenzyme is also found in sera of patients with primary muscular and neuromuscular disorders. Researchers studied cardiac function in two of our patients with electrocardiograms, technetium stannous pyrophosphate scanning, and technetium 99m-labeled erythrocyte gated blood pool imaging and in the third patient by postmortem examination. There was no evidence of myocardial involvement to account for the high serum levels of isoenzyme. Creatine kinase MB in the sera of patients with polymyositis does not necessarily indicate myocardial necrosis.

  17. Proteinase K processing of rabbit muscle creatine kinase

    DEFF Research Database (Denmark)

    Leydier, C; Andersen, Jens S.; Couthon, F

    1997-01-01

    Proteinase K cleaves selectively both cytosolic and mitochondrial isoforms of creatine kinase leading to the appearance of two fragments, a large N-terminal one (K1) and a small C-terminal peptide (K2) which remain associated together. The loss of enzymatic activity correlates with the extent...... of monomer cleavage. N-terminal sequencing of the K2 fragments from rabbit cytosolic and pig mitochondrial creatine kinase shows that these peptides begin with A328 and A324, respectively. Electrospray ionization mass spectrometry demonstrates that K2 peptide is composed of 53 residues (A328-K380). However...

  18. Creatine kinase monitoring in sport medicine.

    Science.gov (United States)

    Brancaccio, Paola; Maffulli, Nicola; Limongelli, Francesco Mario

    2007-01-01

    AREAS OF GENERAL AGREEMENT: Total creatine kinase (CK) levels depend on age, gender, race, muscle mass, physical activity and climatic condition. High levels of serum CK in apparently healthy subjects may be correlated with physical training status, as they depend on sarcomeric damage: strenuous exercise that damages skeletal muscle cells results in increased total serum CK. The highest post-exercise serum enzyme activities are found after prolonged exercise such as ultradistance marathon running or weight-bearing exercises and downhill running, which include eccentric muscular contractions. Total serum CK activity is markedly elevated for 24 h after the exercise bout and, when patients rest, it gradually returns to basal levels. Persistently increased serum CK levels are occasionally encountered in healthy individuals and are also markedly increased in the pre-clinical stages of muscle diseases. Some authors, studying subjects with high levels of CK at rest, observed that, years later, subjects developed muscle weakness and suggested that early myopathy may be asymptomatic. Others demonstrated that, in most of these patients, hyperCKemia probably does not imply disease. In many instances, the diagnosis is not formulated following routine examination with the patients at rest, as symptoms become manifest only after exercise. Some authors think that strength training seems to be safe for patients with myopathy, even though the evidence for routine exercise prescription is still insufficient. Others believe that, in these conditions, intense prolonged exercise may produce negative effects, as it does not induce the physiological muscle adaptations to physical training given the continuous loss of muscle proteins. High CK serum levels in athletes following absolute rest and without any further predisposing factors should prompt a full diagnostic workup with special regards to signs of muscle weakness or other simple signs that, in both athletes and sedentary subjects

  19. Creatine kinase response to high-intensity aerobic exercise in adult-onset muscular dystrophy

    DEFF Research Database (Denmark)

    Andersen, Søren P; Sveen, Marie-Louise; Hansen, Regitze S

    2013-01-01

    We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies.......We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies....

  20. Flunarizine and lamotngine propnyiaxis effects on neuron-specific enolase,S-100,and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Li He; Jingyi Deng; Wendan He

    2008-01-01

    BACKGROUND:Calcium antagonists may act as neuroprotectants,diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically,they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats.OBJECTIVE:To investigate the neuroprotective effects of flunarizine(FNZ),lamotrigine (LTG)and the combination of both drugs,on hypoxic-ischemic brain damage in fetal rats.DESIGN AND SETTING:This randomized,complete block design was performed at the Department of Pediatrics.Shenzhen Fourth People's Hospital,Guangdong Medical College.MATERIALS:Forty pregnant Wistar rats,at gestational day 20,were selected for the experiment and were randomly divided into FNZ,LTG,FNZ+LTG,and model groups,with 10 rats in each group.METHODS:Rats in the FNZ.LTG,and FNZ+LTG groups received intragastric injections of FNZ (0.5 mg/kg/d),LTG(10 mg/kg/d),and FNZ(0.5 mg/kg/d)+LTG(10 mg/kg/d),respectively.Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia.Rats in the modeJ group were not administered any drugs.Three hours after the final administration,eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats.Cesareans were performed at 6,12,24,and 48 hours later;and 5 fetal rats were removed from each mother and kept warm.Twe fetuses without model establishment were removed by planned cesarean at the same time and served as controls.A total of 0.3 mL serum was collected from fetal rats at 6,12,24,and 48 hours,respectively,following birth.MAIN OUTCOME MEASURES:Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA.Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method.RESULTS:Serum concentrations of neuron-specific enolase,S-100,and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats.compared with the non

  1. Hydrolysis and Cyanolysis of DTNB- Modified Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    何飚; 王洪睿; 王希成; 周海梦

    1994-01-01

    The cyanolysis of DTNB-modified creatine kinase(S,S’-di-TNB-CK)has been studied.Itwas found that there exist both cyanolysis and hydrolysis at the same time under the cyanolysis condition de-scribed previously by Degani.DTNB-modified creatine kinase was rapidly hydrolyzed at pH 9.5 in the ab-sence of KCN.The hydrolysis shows biphasic kinetics as seen in the semilogarithmic pseudo-first-order rateplot.The analysis shows that about one S-TNB group/mol of DTNB-modified creatine kinase was rapidly re-leased in the fast phase of the hydrolysis reaction.The further cyanolysis of hydrolytic products showsmonophasic kinetics,and about one S-TNB group/mol of hydrolytic product was also rapidly released.Theabove results show that one of the two TNB-labeled thiol groups situated respectively at two active sites ofthe creatine kinase molecule was rapidly hydrolyzed,and the other was hydrolyzed at a very slow rate.Whenthe hydrolyzed products were cyanolyzed,the other residual TNB group was also released.These resultssuggest that the subunits of creatine kinase are asymmetrically associated.This leads to the differential envi-ronments of the two thiol groups at the active sites of two subunits.The above results also show that withthe TNB release during hydrolysis or cyanolysis,the enzymic activity was also partially recovered at the sametime.The recovery in activity is linearly related to the extent of the regeneration of reactive thiol groups.Therefore,it is suggested that the reactive thiol groups of enzyme are essential for its activity,and they arelocated in the active sites of dimeric enzyme.

  2. Elevated creatine kinase and transaminases in asymptomatic SBMA.

    Science.gov (United States)

    Sorenson, Eric J; Klein, Christopher J

    2007-02-01

    X-linked spinal and bulbar muscular atrophy (SBMA or Kennedy's disease) has a variable prognosis. Most male carriers are affected by their fourth or fifth decade of life, while some remain asymptomatic lifelong. Elevations of serum creatine kinase are well known to occur in clinically manifesting SBMA patients. Elevations prior to the onset of the clinical syndrome have not been reported. Here we report two cases of SBMA presenting with 'idiopathic' elevations of serum transaminases and creatine kinase a decade in advance of their symptomatic onset. These cases emphasize the need to consider SBMA and genetic testing for the androgen receptor trinucleotide CAG expansion in males otherwise healthy with 'idiopathic' elevated creatinine kinase.

  3. Normal values of creatine kinase and of MB-creatine kinase at birth in healthy babies.

    Science.gov (United States)

    Bellieni, Carlo V; Tomasini, Barbara; Bracciali, Carlotta; Buonocore, Giuseppe

    2017-04-20

    Today, few studies have been accomplished in order to determine serum creatine kinase (CK) activity in newborns by considering small groups of babies and without taking into account gestational age (GA) differences. Some authors have demonstrated that neonatal CK activity value at birth is higher than the normal range of CK activity considering for adults or older children. The objective of this study is to assess normal values of CK and MB-CK in neonatal blood, according to babies' GA. We retrieved the clinical files of 140 babies admitted into Siena Hospital NICU in a 2-years period, when CK was assessed routinely to all babies at birth. We selected files from 114 newborns and we divided the cohort into group A (non-stressed; n=41) and group B (stressed; n=73) on the basis of Apgar score and signs of neurological lesions. We compared CK and MB-CK values in the two groups according to GA. Mean CK value of the 41 non-stressed babies' samples: 413 IU/L (232 SD). CK significantly increases with GA. No differences are present in total CK activity between stressed vs non-stressed babies; but a significant difference appears in these two groups for MB-CK (mean values: 456 vs 175 IU/L). This is the first study that compares CK and MB-CK values at birth according to the GA of the babies. CK values increase with GA, and stressed babies have higher MB-CK values than the non-stressed babies. These reference values are important for clinical practice.

  4. Creatine kinase activity in dogs with experimentally induced acute inflammation

    Directory of Open Access Journals (Sweden)

    Dimitrinka Zapryanova

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

  5. The value of serum creatine kinase in early diagnosis of heterotopic ossification.

    Science.gov (United States)

    Sherman, Andrew L; Williams, Joan; Patrick, Lornette; Banovac, Kresimir

    2003-01-01

    Heterotopic ossification (HO) is a complication of spinal cord injury (SCI) characterized by formation of ectopic bone. Early diagnosis is critical, but available diagnostic methods have drawbacks. Serum creatine kinase may be a marker for the development and severity of HO. 18 SCI patients with diagnosed HO based on clinical findings and bone scintigraphy. Serum creatine kinase levels were taken at the time of diagnosis of HO and during subsequent etidronate therapy. Of the 14 patients with normal creatine kinase values, 13 had no evidence of HO on follow-up radiographic examination. Of the 4 patients with elevated creatine kinase, all developed radiographic signs of HO. Elevated serum creatine kinase may be associated with a more aggressive course of HO as well as resistance to etidronate therapy. Further studies are needed to determine whether creatine kinase may serve as a marker for early, active HO.

  6. Interfacial behavior of cytoplasmic and mitochondrial creatine kinase oligomeric states.

    Science.gov (United States)

    Vernoux, Nathalie; Granjon, Thierry; Marcillat, Olivier; Besson, Françoise; Vial, Christian

    2006-03-01

    Adsorption to the air/water interface of isoenzymes of creatine kinase was investigated using surface pressure-area isotherms and Brewster angle microscopy (BAM) observations. Octameric mitochondrial creatine kinase (mtCK) exhibits a significant affinity for the air/water interface. Whatever the mode of formation of the interfacial film, i.e., injection of the protein in the subphase or spreading onto the buffer surface, the final arrangement and conformation adopted by mtCK molecules lead to a similar result. In contrast, the dimeric isoenzymes mtCK and cytosolic MMCK do not induce any surface pressure variation. However, when the subphase contains 0.3M NaCl, both isoenzymes adsorb to the interface. When treated with 0.8 or 3M GdnHCl, muscle creatine kinase (MMCK) becomes surface active and occupies a greater surface than mtCK. This result contrasts with previous observations, often derived from monomeric proteins, that their surface activity is increased upon unfolding. It underlines the possible influence exerted by the protein oligomeric state on its interfacial activity. At a subphase pH of 8.8, which corresponds to the pI of octameric mtCK, the profiles of the isotherms obtained with dimeric and octameric states and the resistance to compression of the protein monolayers are significantly affected when compared to those recorded at pH 7.4. These data suggest that the octamer is more hydrophobic than the dimer and may contribute to explaining why octamers bind to the inner mitochondrial membrane while dimers do not. Copyright 2005 Wiley Periodicals, Inc.

  7. Creatine kinase deficiency in striated mouse muscle : biochemical and physiological studies

    NARCIS (Netherlands)

    Veld, Frank ter

    2003-01-01

    The balance between ATP energy demand and supply is essential in muscle cells. The creatine kinase system fulfils both a transporting and buffering role in muscle cells, whereby fluctuations in ATP free-energy demand can be counterbalanced. Removal of the creatine kinase proteins with the aid of

  8. Creatine kinase deficiency in striated mouse muscle : biochemical and physiological studies

    NARCIS (Netherlands)

    Veld, Frank ter

    2003-01-01

    The balance between ATP energy demand and supply is essential in muscle cells. The creatine kinase system fulfils both a transporting and buffering role in muscle cells, whereby fluctuations in ATP free-energy demand can be counterbalanced. Removal of the creatine kinase proteins with the aid of gen

  9. Characterization of the Partially Folded Monomeric Intermediate of Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    朴龙斗; 周海梦

    2002-01-01

    The importance of understanding the protein folding pathway and intermediates is well recognized on the basis of extensive studies of protein folding in vitro and in vivo. Creatine kinase (CK) is a typical model for studying unfolding and refolding of proteins due to several interesting properties. Recent studies on the folding of CK show that its partially folded monomeric intermediate is present kinetically and is stable at equilibrium. The present paper contains 33 References as a mini review to characterize the properties of CK from studies on the CK folding pathway. Characterization of these intermediates is an essential step toward understanding the mechanism of protein folding. Some well-determined schemes are suggested as protein folding models.

  10. Break point of serum creatine kinase release after endurance exercise.

    Science.gov (United States)

    Totsuka, Manabu; Nakaji, Shigeyuki; Suzuki, Katsuhiko; Sugawara, Kazuo; Sato, Koki

    2002-10-01

    We investigated whether there is a break point of creatine kinase (CK) release after daily endurance exercise and whether CK response depends on individual physical characteristics. Fifteen healthy young men performed 90 min of bicycle exercise for 3 consecutive days. Body composition, properties of the quadriceps femoris muscle (QFM), and aerobic and anaerobic capacities were estimated before the test. Blood samples were obtained 22 times during the experimental period. Endurance exercise significantly elevated serum CK from 3 h after the first exercise session (P 500 IU/l of CK) and low responders (LR; break point of CK release after endurance exercise under these conditions is 300-500 IU/l, two or three times higher than in the resting condition, and is associated with properties of the QFM.

  11. Immunoglobulin-associated creatine kinase masquerading as macro-creatine kinase type 2 in a statin user.

    Science.gov (United States)

    Loh, Tze Ping; Ang, Yan Hoon; Neo, Siew Fong; Yin, Cecilia; Wong, Moh Sim; Leong, Sai Mun; Saw, Sharon; Sethi, Sunil K

    2012-01-01

    Macro-creatine kinase (CK) is a cause of falsely elevated CK. Macro-CK type 1 is immunoglobulin-associated CK; type 2 is polymeric mitochondrial-CK. An elderly asymptomatic lady had an elevated CK level after receiving statin therapy. Her CK gel electrophoresis analysis demonstrated coexisting macro-CK type 1 and type 2 patterns. Further analysis by immunofixation and mixing this patient's serum with CK control material revealed an IgG-associated macro-CK that mimicked the electrophoretic pattern of macro-CK type 2. This highly unusual discovery suggests the possibility of the misinterpretation of macro-CK type 1 as macro-CK type 2. Falsely elevated CK is still common despite modern laboratory instrumentation and should be investigated.

  12. Mice lacking brain-type creatine kinase activity show defective thermoregulation

    Science.gov (United States)

    Streijger, Femke; Pluk, Helma; Oerlemans, Frank; Beckers, Gaby; Bianco, Antonio C.; Ribeiro, Miriam O.; Wieringa, Bé; Van der Zee, Catharina E.E.M.

    2010-01-01

    The cytosolic brain-type creatine kinase and mitochondrial ubiquitous creatine kinase (CK-B and UbCKmit) are expressed during the prepubescent and adult period of mammalian life. These creatine kinase (CK) isoforms are present in neural cell types throughout the central and peripheral nervous system and in smooth muscle containing tissues, where they have an important role in cellular energy homeostasis. Here, we report on the coupling of CK activity to body temperature rhythm and adaptive thermoregulation in mice. With both brain-type CK isoforms being absent, the body temperature reproducibly drops ~1.0°C below normal during every morning (inactive) period in the daily cycle. Facultative non-shivering thermogenesis is also impaired, since CK−−/−− mice develop severe hypothermia during 24 h cold exposure. A relationship with fat metabolism was suggested because comparison of CK−−/−− mice with wildtype controls revealed decreased weight gain associated with less white and brown fat accumulation and smaller brown adipocytes. Also, circulating levels of glucose, triglycerides and leptin are reduced. Extensive physiological testing and uncoupling protein1 analysis showed, however, that the thermogenic problems are not due to abnormal responsiveness of brown adipocytes, since noradrenaline infusion produced a normal increase of body temperature. Moreover, we demonstrate that the cyclic drop in morning temperature is also not related to altered rhythmicity with reduced locomotion, diminished food intake or increased torpor sensitivity. Although several integral functions appear altered when CK is absent in the brain, combined findings point into the direction of inefficient neuronal transmission as the dominant factor in the thermoregulatory defect. PMID:19419668

  13. Creatine kinase inhibition lowers systemic arterial blood pressure in spontaneously hypertensive rats: a randomized controlled trial.

    Science.gov (United States)

    Karamat, Fares A; Oudman, Inge; Haan, Yentl C; van Kuilenburg, Andre B P; Leen, Rene; Danser, Jan A H; Leijten, Frank P J; Ris-Stalpers, Carrie; van Montfrans, Gert A; Clark, Joseph F; Brewster, Lizzy M

    2016-12-01

    Creatine kinase is reported to be a main predictor of blood pressure (BP) in the general population, with a strong correlation between resistance artery creatine kinase expression and clinical BP in humans. The enzyme rapidly regenerates ATP near cytoplasmic ATPases involved in pressor responses, including resistance artery contractility and renal sodium retention. Therefore, we assessed whether creatine kinase inhibition reduces BP. We implemented the 'Animal Research: Reporting of In Vivo Experiments' guideline. In a 4-week randomized controlled trial, male 16-week-old spontaneously hypertensive rats (N = 16) were randomly assigned to the specific competitive creatine kinase inhibitor beta-guanidinopropionic acid (3%)-supplemented chow vs. standard chow. BP measured by the tail-cuff method was the main outcome. Other outcomes included vasodilation in isolated arteries and renal renin expression. Creatine kinase inhibition reduced BP safely and reversibly. Mean baseline BP of, respectively, 191.5 (standard error 4.3) mmHg SBP and 143.1 (4.1) mmHg DBP was reduced by, respectively, 42.7 (5.5) mmHg SBP and 35.6 (5.0) mmHg DBP (P creatine kinase inhibition. Our data indicate that modulation of the creatine kinase system is a potential novel treatment target for hypertension.

  14. Effects of Glycerol in the Refolding and Unfolding of Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    欧文斌; 朴龙斗; 孟凡国; 周海梦

    2002-01-01

    The effects of glycerol in the refolding, reactivation, unfolding, and inactivation of guanidine- denatured creatine kinase were studied by observing the fluorescence emission spectra and the circular dichroism spectra, and by recovery and inactivation of enzymatic activity and aggregation. The results show that low concentrations of glycerol (<25%) improve the refolding yields of creatine kinase, but high glycerol concentrations decrease its recovery. Glycerol favors the secondary structural formation and inhibits aggregation of creatine kinase as proline does. These systematic observations further support the suggestion that low concentrations of glycerol possibly play a chaperone role in the refolding of creatine kinase. In addition, glycerol reduces the inactivation and unfolding rate of creatine kinase, increases the change in transition free energy of unfolding (ΔΔGu) and stabilizes its active conformation relative to the partially unfolded state with no glycerol. In the presence of glycerol, the inactivation and unfolding dynamics of creatine kinase are related to glycerol concentrations. Glycerol blocks the exposure of hydrophobic areas and the dissociation of dimers, and protects creatine kinase against guanidine denaturation in a concentration-dependent manner. This study suggests that glycerol as an energy substrate for metabolism and organic components in vivo, assists correct protein folding, maintains adequate rates of enzymatic catalysis and stabilizes the protein secondary and tertiary conformations.

  15. Impaired brain creatine kinase activity in Huntington's disease.

    Science.gov (United States)

    Zhang, S F; Hennessey, T; Yang, L; Starkova, N N; Beal, M F; Starkov, A A

    2011-01-01

    Huntington's disease (HD) is associated with impaired energy metabolism in the brain. Creatine kinase (CK) catalyzes ATP-dependent phosphorylation of creatine (Cr) into phosphocreatine (PCr), thereby serving as readily available high-capacity spatial and temporal ATP buffering. Substantial evidence supports a specific role of the Cr/PCr system in neurodegenerative diseases. In the brain, the Cr/PCr ATP-buffering system is established by a concerted operation of the brain-specific cytosolic enzyme BB-CK and ubiquitous mitochondrial uMt-CK. It is not yet established whether the activity of these CK isoenzymes is impaired in HD. We measured PCr, Cr, ATP and ADP in brain extracts of 3 mouse models of HD - R6/2 mice, N171-82Q and HdhQ(111) mice - and the activity of CK in cytosolic and mitochondrial brain fractions from the same mice. The PCr was significantly increased in mouse HD brain extracts as compared to nontransgenic littermates. We also found an approximately 27% decrease in CK activity in both cytosolic and mitochondrial fractions of R6/2 and N171-82Q mice, and an approximately 25% decrease in the mitochondria from HdhQ(111) mice. Moreover, uMt-CK and BB-CK activities were approximately 63% lower in HD human brain samples as compared to nondiseased controls. Our findings lend strong support to the role of impaired energy metabolism in HD, and point out the potential importance of impairment of the CK-catalyzed ATP-buffering system in the etiology of HD. Copyright © 2010 S. Karger AG, Basel.

  16. 2-Chloromercuri-4-nitrophenol-modified Sites of Creatine Kinase Confirmed by FPLC

    Institute of Scientific and Technical Information of China (English)

    张平城

    1994-01-01

    MNP-modified tryptic peptides of creatine kinase have been separated with two-dimensional electrophoresis, but the location of the SH groups of creatine kinase modified by MNP still seemed to be vague until recently (Laue, M. C. & Quiocho, F. A. , 1977). Two peptides have now been found to be the MNP-modified peptides with reversed-phase FPLC methods, and the amino acid compositions of these two peptides are in agreement with those of the two peptides around Cys-145 and Cys-253, respectively. These findings indicate that the two buried SH groups of creatine kinase have been modified by MNP.

  17. Method of empirical dependences in estimation and prediction of activity of creatine kinase isoenzymes in cerebral ischemia

    Science.gov (United States)

    Sergeeva, Tatiana F.; Moshkova, Albina N.; Erlykina, Elena I.; Khvatova, Elena M.

    2016-04-01

    Creatine kinase is a key enzyme of energy metabolism in the brain. There are known cytoplasmic and mitochondrial creatine kinase isoenzymes. Mitochondrial creatine kinase exists as a mixture of two oligomeric forms - dimer and octamer. The aim of investigation was to study catalytic properties of cytoplasmic and mitochondrial creatine kinase and using of the method of empirical dependences for the possible prediction of the activity of these enzymes in cerebral ischemia. Ischemia was revealed to be accompanied with the changes of the activity of creatine kinase isoenzymes and oligomeric state of mitochondrial isoform. There were made the models of multiple regression that permit to study the activity of creatine kinase system in cerebral ischemia using a calculating method. Therefore, the mathematical method of empirical dependences can be applied for estimation and prediction of the functional state of the brain by the activity of creatine kinase isoenzymes in cerebral ischemia.

  18. Histochemical detection of creatine kinase in the electrocyte of Electrophorus electricus (L.).

    Science.gov (United States)

    Taffarel, M; Silva, C B; Machado, R D; Hassón-Voloch, A

    1987-01-01

    Detection of creatine kinase, which catalyzes the conversion of ADP and phosphocreatine to ATP and creatine, was performed on the electrocyte of Electrophorus electricus (L.) using a histoenzymological method based on the formation of blue colored formazan. The results indicate that the enzyme is mainly located within the cytoplasm of the electrolyte.

  19. An examination of some factors influencing creatine kinase in the blood of patients with muscular dystrophy.

    Science.gov (United States)

    Jackson, M J; Round, J M; Newham, D J; Edwards, R H

    1987-01-01

    The natural variability of plasma creatine kinase activity has been examined in patients suffering from muscular dystrophy and in normal subjects. The coefficient of variation of the plasma creatine kinase activities was found to be large (approximately 35%) in both patients with Duchenne muscular dystrophy and normal control subjects. A comparison of the plasma activities of creatine kinase with other muscle-derived enzymes suggests that the cause of this variability is changes in the release of enzymes from muscle. Data obtained concerning the effect of physical activity on plasma creatine kinase activity are contradictory, but several young patients with Duchenne muscular dystrophy and a very high creatine kinase activity (greater than 5000 IU/liter) showed a decreased activity following admission to hospital. An estimate of the rate of efflux of certain kinase from muscle has been made, indicating that young ambulant patients with Duchenne muscular dystrophy have a grossly elevated muscle creatine kinase efflux (495.0 +/- 61.3 IU/kg muscle/hr) compared to control subjects (1.4 +/- 0.5 IU/kg muscle/hr).

  20. Muscle recovery after a session of resistance training monitored through serum creatine kinase

    National Research Council Canada - National Science Library

    de Castro, Antonio Paulo Andre; Vianna, Jeferson Macedo; Damasceno, Vinicius de Oliveira; de Matos, Dihogo Gama; Filho, Mauro Lucio Mazini; Reis, Victor Manuel Machado

    2011-01-01

    De Castro APA, Vianna JM, Damasceno VO, Matos DG, Mazini Filho ML, Reis VMM. Muscle Recovery after a Session of Resistance Training Monitored through Serum Creatine Kinase. JEPonline 2011; 14(5):38-45...

  1. Exercise responses in patients with chronically high creatine kinase levels.

    Science.gov (United States)

    Cooper, Christopher B; Dolezal, Brett A; Neufeld, Eric V; Shieh, Perry; Jenner, John R; Riley, Marshall

    2017-08-01

    Elevated serum creatine kinase (CK) is often taken to reflect muscle disease, but many individuals have elevated CK without a specific diagnosis. How elevated CK reflects muscle metabolism during exercise is not known. Participants (46 men, 48 women) underwent incremental exercise testing to assess aerobic performance, cardiovascular response, and ventilatory response. Serum lactate, ammonia, and CK were measured at rest, 4 minutes into exercise, and 2 minutes into recovery. High-CK and control subjects demonstrated similar aerobic capacities and cardiovascular responses to incremental exercise. Those with CK ≥ 300 U/L exhibited significantly higher lactate and ammonia levels after maximal exercise, together with increased ventilatory responses, whereas those with CK ≥200 U/L but ≤ 300 U/L did not. We recommend measurement of lactate and ammonia profiles during a maximal incremental exercise protocol to help identify patients who warrant muscle biopsy to rule out myopathy. Muscle Nerve 56: 264-270, 2017. © 2016 Wiley Periodicals, Inc.

  2. Serum creatine kinase relationship to postural constraints in manual work.

    Science.gov (United States)

    Mairiaux, P; Bettonville, M N; Mawet, M; Malchaire, J

    1986-01-01

    Serum creatine kinase (CK) variations during work and subjective assessments of postural discomfort were analysed in 30 workers assigned to three different tasks in a rolling mill. After four days of work, serum CK levels were significantly increased above control levels. No difference was found between the tasks studied. Inter-individual variability in CK response was large: a marked CK increase was only seen in 21 workers, while 5 workers showed a marked CK decrease. The postural discomfort sensations increased with work in each group, with their location in the body being related to the characteristics of each task or workplace. No relationship was found between the postural discomfort scores and CK changes. Results showed that determination of an individual baseline CK level was difficult to achieve in an occupational setting. It is concluded that CK variations cannot reliably be used in the field for detection of individuals exposed to excessive postural constraints. Their use as a screening tool in groups of workers assigned to similar tasks deserves further study.

  3. Macromolecular Crowding Enhances Thermal Stability of Rabbit Muscle Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    ZHU Jiang; HE Huawei; LI Sen

    2008-01-01

    The effect of dextran on the conformation (or secondary structure) and thermal stability of creatine kinase (CK) was studied using the far-ultraviolet (UV) circular dichroism (CD) spectra.The results showed that lower concentrations of dextran (less than 60 g/L) induced formation of the secondary CK structures.However,the secondary structure content of CK decreased when the dextran concentrations exceeded 60 g/L.Thermally induced transition curves were measured for CK in the presence of different concentrations of dextran by far-UV CD.The thermal transition curves were fitted to a two-state model by a nonlinear,least-squares method to obtain the transition temperature of the unfolding transition.An increase in the tran- sition temperature was observed with the increase of the dextran concentration.These observations qualita-tively accord with predictions of a previously proposed model for the effect of intermolecular excluded volume (macromolecular crowding) on protein stability and conformation.These findings imply that the effects of macromolecular crowding can have an important influence on our understanding of how protein folding oc-curs in vivo.

  4. Creatine kinase-MB: the journey to obsolescence.

    Science.gov (United States)

    Singh, Gurmukh; Baweja, Paramdeep S

    2014-03-01

    To evaluate the clinical utility of and demand for the creatine kinase (CK)-MB assay. We examined the number of CK-MB tests from 2007 through 2013 while we progressively deemphasized their use. We first removed CK-MB from the acute coronary syndrome (ACS) panel and then from the main menu and observed the demand for the test. We also reviewed patient medical records to assess the appropriateness of its use. After removing CK-MB from the ACS panel, the test volume dropped from around 12,000 per year to about 150 per year. In reviewing the records of 171 patients who had CK-MB determination done over a 28-month period, we discovered that CK-MB contributed to the diagnosis in only one patient, although it was not essential. Since removing CK-MB from the laboratory menu, two CK-MB tests were ordered in 4 months, and neither added value. CK-MB determinations do not add value to information available from the troponin assay and can be safely removed from the laboratory menu.

  5. Resistance artery creatine kinase mRNA and blood pressure in humans.

    Science.gov (United States)

    Karamat, Fares A; Oudman, Inge; Ris-Stalpers, Carrie; Afink, Gijs B; Keijser, Remco; Clark, Joseph F; van Montfrans, Gert A; Brewster, Lizzy M

    2014-01-01

    Hypertension remains the main risk factor for cardiovascular death. Environmental and biological factors are known to contribute to the condition, and circulating creatine kinase was reported to be the main predictor of blood pressure in the general population. This was proposed to be because of high resistance artery creatine kinase-BB rapidly regenerating ATP for vascular contractility. Therefore, we assessed whether creatine kinase isoenzyme mRNA levels in human resistance arteries are associated with blood pressure. We isolated resistance-sized arteries from omental fat donated by consecutive women undergoing uterine fibroid surgery. Blood pressure was measured in the sitting position. Vessels of 13 women were included, 6 normotensive and 7 hypertensive, mean age 42.9 years (SE, 1.6) and mean systolic/diastolic blood pressure, 144.8 (8.0)/86.5 (4.3) mm Hg. Arteriolar creatine kinase isoenzyme mRNA was assessed using quantitative real-time polymerase chain reaction. Normalized creatine kinase B mRNA copy numbers, ranging from 5.2 to 24.4 (mean, 15.0; SE, 1.9), showed a near-perfect correlation with diastolic blood pressure (correlation coefficient, 0.9; 95% confidence interval, 0.6-1.0) and were well correlated with systolic blood pressure, with a 90% relative increase in resistance artery creatine kinase B mRNA in hypertensives compared with normotensives, normalized copy numbers were, respectively, 19.3 (SE, 2.0) versus 10.1 (SE, 2.1), P=0.0045. To our knowledge, this is the first direct evidence suggesting that resistance artery creatine kinase mRNA expression levels concur with blood pressure levels, almost doubling with hypertension. These findings add to the evidence that creatine kinase might be involved in the vasculature's pressor responses.

  6. Dependence of myosin-ATPase on structure bound creatine kinase in cardiac myfibrils from rainbow trout and freshwater turtle

    DEFF Research Database (Denmark)

    Haagensen, L.; Jensen, D.H.; Gesser, Hans

    2008-01-01

    by the pyruvate kinase reaction alone or together with the amount of creatine formed, when myofibrillar bound creatine kinase was activated with phosphocreatine. The steady-state concentration of ADP in the solution was varied through the activity of pyruvate kinase added to the solution. For rainbow trout...... was restored by adding creatine kinase to the solution. Hence, the results suggest that myofibril-bound creatine kinase is needed to fully activate the myosin-ATPase activity in hearts from ectothermic vertebrates despite their low energy turn-over relative to endothermic species....

  7. Creatine inhibits adipogenesis by downregulating insulin-induced activation of the phosphatidylinositol 3-kinase signaling pathway.

    Science.gov (United States)

    Lee, Nayeon; Kim, Inhee; Park, Soojeong; Han, Dasol; Ha, Soobong; Kwon, Mookwang; Kim, Juwan; Byun, Sung-Hyun; Oh, Wonil; Jeon, Hong Bae; Kweon, Dae-Hyuk; Cho, Jae Youl; Yoon, Keejung

    2015-04-15

    Creatine is a nitrogenous organic acid known to function in adenosine triphosphate (ATP) metabolism. Recent evidence indicates that creatine regulates the differentiation of mesenchymal stem cells (MSCs) in processes such as osteogenesis and myogenesis. In this study, we show that creatine also has a negative regulatory effect on fat cell formation. Creatine inhibits the accumulation of cytoplasmic triglycerides in a dose-dependent manner irrespective of the adipogenic cell models used, including a C3H10T1/2 MSC line, 3T3-L1 preadipocytes, and primary human MSCs. Consistently, a dramatic reduction in mRNA expression of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), glucose transporters, 1 and 4 (Glut1, Glut4), and adipocyte markers, aP2 and adipsin, was observed in the presence of creatine. Creatine appears to exert its inhibitory effects on adipogenesis during early differentiation, but not late differentiation, or proliferation stages through inhibition of the PI3K-Akt-PPARγ signaling pathway. In an in vivo model, administration of creatine into mice resulted in body mass increase without fat accumulation. In summary, our results indicate that creatine downregulates adipogenesis through inhibition of phosphatidylinositol 3-kinase (PI3K) activation and imply the potent therapeutic value of creatine in treating obesity and obesity-related metabolic disorders.

  8. Muscle-Tendon Unit Properties during Eccentric Exercise Correlate with the Creatine Kinase Response

    Directory of Open Access Journals (Sweden)

    Kirsty M. Hicks

    2017-09-01

    Full Text Available Aim: The aim of this paper was to determine whether; (1 patella tendon stiffness, (2 the magnitude of vastus lateralis fascicle lengthening, and (3 eccentric torque correlate with markers of exercise induced muscle damage.Method: Combining dynamometry and ultrasonography, patella tendon properties and vastus lateralis architectural properties were measured pre and during the first of six sets of 12 maximal voluntary eccentric knee extensions. Maximal isometric torque loss and creatine kinase activity were measured pre-damage (−48 h, 48, 96, and 168 h post-damage as markers of exercise-induced muscle damage.Results: A significant increase in creatine kinase (883 ± 667 UL and a significant reduction in maximal isometric torque loss (21% was reported post-eccentric contractions. Change in creatine kinase from pre to peak significantly correlated with the relative change in vastus lateralis fascicle length during eccentric contractions (r = 0.53, p = 0.02 and with eccentric torque (r = 0.50, p = 0.02. Additionally, creatine kinase tended to correlate with estimated patella tendon lengthening during eccentric contractions (p < 0.10. However, creatine kinase did not correlate with resting measures of patella tendon properties or vastus lateralis properties. Similarly, torque loss did not correlate with any patella tendon or vastus lateralis properties at rest or during eccentric contractions.Conclusion: The current study demonstrates that the extent of fascicle strain during eccentric contractions correlates with the magnitude of the creatine kinase response. Although at rest, there is no relationship between patella tendon properties and markers of muscle damage; during eccentric contractions however, the patella tendon may play a role in the creatine kinase response following EIMD.

  9. Presence of (phospho)creatine in developing and adult skeletal muscle of mice without mitochondrial and cytosolic muscle creatine kinase isoforms.

    NARCIS (Netherlands)

    Zandt, H.J.A. in t; Groof, A.J.C. de; Renema, W.K.J.; Oerlemans, F.T.J.J.; Klomp, D.W.J.; Wieringa, B.; Heerschap, A.

    2003-01-01

    We assessed the relationship between phosphocreatine (PCr) and creatine (Cr) content and creatine kinase (CK) activity in skeletal muscle of mice. The PCr and total Cr (tCr) concentrations, as well as CK activity, in hindlimb muscles of mice, with or without the cytosolic and mitochondrial isoforms

  10. Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8 by the Janus Kinase JAK3

    Directory of Open Access Journals (Sweden)

    Myriam Fezai

    2015-12-01

    Full Text Available Background: The creatine transporter CreaT (SLC6A8, a Na+,Cl- coupled transporter is expressed in diverse tissues including the brain. Genetic defects of SLC6A8 result in mental retardation with seizures. The present study explored the regulation of CreaT by Janus kinase JAK3, which is expressed in a variety of tissues including the brain and participates in the regulation of cell survival and differentiation of neuronal precursor cells. Methods: CreaT was expressed in Xenopus laevis oocytes with or without wild-type JAK3, constitutively active A568VJAK3 and inactive K851AJAK3. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. Results: Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes co-expression of JAK3 or A568VJAK3, but not co-expression of K851AJAK3 was followed by a significant decrease of creatine induced current. According to kinetic analysis JAK3 significantly decreased the maximal creatine transport rate. In CreaT and JAK3 expressing oocytes the creatine induced current was significantly increased by JAK3 inhibitor WHI-P154 (22 µM. Conclusion: JAK3 is a powerful negative regulator of the creatine transporter CreaT.

  11. Tyrosine inhibits creatine kinase activity in cerebral cortex of young rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2011-09-01

    Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II, where tyrosine levels are highly elevated in tissues and physiological fluids of affected patients. Tyrosinemia type II is a disorder of autosomal recessive inheritance characterized by neurological symptoms similar to those observed in patients with creatine deficiency syndromes. Considering that the mechanisms of brain damage in these disorders are poorly known, in the present study our main objective was to investigate the in vivo and in vitro effects of different concentrations and preincubation times of tyrosine on cytosolic and mitochondrial creatine kinase activities of the cerebral cortex from 14-day-old Wistar rats. The cytosolic CK was reduced by 15% at 1 mM and 32% at 2 mM tyrosine. Similarly, the mitochondrial CK was inhibited by 15% at 1 mM and 22% at 2 mM tyrosine. We observed that the inhibition caused by tyrosine was concentration-dependent and was prevented by reduced glutathione. Results also indicated that mitochondrial, but not cytosolic creatine kinase activity was inhibited by tyrosine in a time-dependent way. Finally, a single injection of L-Tyrosine methyl ester administered i.p. decreased cytosolic (31%) and mitochondrial (18%) creatine kinase activities of brain cortex from rats. Considering that creatine kinase is an enzyme dependent of thiol residues for its function and tyrosine induces oxidative stress, the results suggest that the inhibition caused by tyrosine might occur by oxidation of essential sulfhydryl groups of the enzyme. In case this also occurs in patients with tyrosinemia, it is possible that creatine kinase inhibition may contribute to the neurological dysfunction characteristic of tyrosinemia.

  12. AMP kinase expression and activity in human skeletal muscle: effects of immobilization, retraining, and creatine supplementation

    DEFF Research Database (Denmark)

    Eijnde, Bert O.; Derave, Wim; Wojtaszewski, Jørgen

    2005-01-01

    The effects of leg immobilization and retraining in combination with oral creatine intake on muscle AMP-activated protein kinase (AMPK) protein expression and phosphorylation status were investigated. A double-blind trial was performed in young healthy volunteers (n = 22). A cast immobilized the ...

  13. Cellular remodeling in creatine kinase-deficient muscles : adaptive changes and regulatory mechanisms

    NARCIS (Netherlands)

    Groof, A.J.C. de

    2002-01-01

    Optimal balancing of production, distribution and consumption of cellular energy is of pivotal importance for every cell in the body. Therefore, all cells possess an elaborate network of enzymes that help in safeguarding energy homeostasis. Members of the creatine kinase (CK) family of enzymes play

  14. Creatine Kinase Activity Weakly Correlates to Volume Completed Following Upper Body Resistance Exercise

    Science.gov (United States)

    Machado, Marco; Willardson, Jeffrey M.; Silva, Dailson P.; Frigulha, Italo C.; Koch, Alexander J.; Souza, Sergio C.

    2012-01-01

    In the current study, we examined the relationship between serum creatine kinase (CK) activity following upper body resistance exercise with a 1- or 3-min rest between sets. Twenty men performed two sessions, each consisting of four sets with a 10-repetition maximum load. The results demonstrated significantly greater volume for the 3-min…

  15. Creatine Kinase Activity Weakly Correlates to Volume Completed Following Upper Body Resistance Exercise

    Science.gov (United States)

    Machado, Marco; Willardson, Jeffrey M.; Silva, Dailson P.; Frigulha, Italo C.; Koch, Alexander J.; Souza, Sergio C.

    2012-01-01

    In the current study, we examined the relationship between serum creatine kinase (CK) activity following upper body resistance exercise with a 1- or 3-min rest between sets. Twenty men performed two sessions, each consisting of four sets with a 10-repetition maximum load. The results demonstrated significantly greater volume for the 3-min…

  16. Creatine kinase in the serum of patients with acute infections of the central nervous system

    DEFF Research Database (Denmark)

    Peterslund, N A; Heinsvig, E M; Christensen, K D

    1985-01-01

    Serum creatine kinase was assessed in 94 consecutive patients without convulsions admitted to hospital due to suspicion of infection of the central nervous system. No reliable discrimination between patients with aseptic and those with bacterial meningitis was obtained. Patients with bacterial...

  17. Oligosaccharide and creatine supplementation on glucose and urea nitrogen in blood and serum creatine kinase in basketball athletes.

    Science.gov (United States)

    Shi, Daling

    2005-01-01

    The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups: group A (supplementation of Cr alone), group B (supplementation of oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D (placebo control group). By using orthogonal L4 table (2(3)), the experiment was performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr and their correlation. Each factor had two levels: supplementation and no-supplementation. The results showed that the supplementation of CHO or Cr alone, combined supplementation of CHO and Cr could significantly reduce the glucose, urea nitrogen levels in blood and serum CK activity after competition in the athletes. Moreover, the effects of combined supplementation of CHO and Cr were more satisfactory. It was concluded that supplementation of CHO and Cr could promote the recovery of physical performance and athletic abilities after athletics in basketball athletes.

  18. Oligosaccharide and Creatine Supplementation on Glucose and Urea Nitrogen in Blood and Serum Creatine Kinase in Basketball Athletes

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups: group A (supplementation of Cr alone), group B (supplementation of oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D (placebo control group). By using orthogonal L4 table (23), the experiment was performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr and their correlation. Each factor had two levels: supplementation and no-supplementation. The results showed that the supplementation of CHO or Cr alone, combined supplementation of CHO and Cr could significantly reduce the glucose, urea nitrogen levels in blood and serum CK activity after competition in the athletes. Moreover, the effects of combined supplementation of CHO and Cr were more satisfactory. It was concluded that supplementation of CHO and Cr could promote the recovery of physical performance and athletic abilities after athletics in basketball athletes.

  19. Computational Simulations to Predict Creatine Kinase-Associated Factors: Protein-Protein Interaction Studies of Brain and Muscle Types of Creatine Kinases

    Directory of Open Access Journals (Sweden)

    Wei-Jiang Hu

    2011-01-01

    Full Text Available Creatine kinase (CK; EC 2.7.3.2 is related to several skin diseases such as psoriasis and dermatomyositis. CK is important in skin energy homeostasis because it catalyzes the reversible transfer of a phosphoryl group from MgATP to creatine. In this study, we predicted CK binding proteins via the use of bioinformatic tools such as protein-protein interaction (PPI mappings and suggest the putative hub proteins for CK interactions. We obtained 123 proteins for brain type CK and 85 proteins for muscle type CK in the interaction networks. Among them, several hub proteins such as NFKB1, FHL2, MYOC, and ASB9 were predicted. Determination of the binding factors of CK can further promote our understanding of the roles of CK in physiological conditions.

  20. Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase.

    Science.gov (United States)

    Li, Quanjie; Fan, Shuai; Li, Xiaoyu; Jin, Yuanyuan; He, Weiqing; Zhou, Jinming; Cen, Shan; Yang, ZhaoYong

    2016-12-02

    Human ubiquitous mitochondrial creatine kinase (uMtCK) is responsible for the regulation of cellular energy metabolism. To investigate the phosphoryl-transfer mechanism catalyzed by human uMtCK, in this work, molecular dynamic simulations of uMtCK∙ATP-Mg(2+)∙creatine complex and quantum mechanism calculations were performed to make clear the puzzle. The theoretical studies hereof revealed that human uMtCK utilizes a two-step dissociative mechanism, in which the E227 residue of uMtCK acts as the catalytic base to accept the creatine guanidinium proton. This catalytic role of E227 was further confirmed by our assay on the phosphatase activity. Moreover, the roles of active site residues in phosphoryl transfer reaction were also identified by site directed mutagenesis. This study reveals the structural basis of biochemical activity of uMtCK and gets insights into its phosphoryl transfer mechanism.

  1. Carrier detection in Becker muscular dystrophy using creatine kinase estimation and DNA analysis.

    Science.gov (United States)

    Kingston, H M; Sarfarazi, M; Newcombe, R G; Willis, N; Harper, P S

    1985-04-01

    Serum creatine kinase levels in 39 control females and 59 obligate carriers of Becker muscular dystrophy (BMD) have been used to construct likelihood ratios for carrier detection. In 24 possible carriers of BMD, analysis of DNA with X chromosome specific DNA probes linked to the dystrophy gene, has been used in conjunction with creatine kinase measurement to calculate final risk estimates of carrier status. Incorporation of information from probe genotype into the Bayesian calculation, enables a substantially lower risk to be deliniated for some possible carriers of the BMD gene. Thus, although the existing DNA probes are not sufficiently closely linked to BMD to be used in prenatal diagnosis, they can make a major contribution to genetic counseling by refining the estimated probability of carrier status.

  2. Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain.

    Science.gov (United States)

    Réus, Gislaine Z; Stringari, Roberto B; Rezin, Gislaine T; Fraga, Daiane B; Daufenbach, Juliana F; Scaini, Giselli; Benedet, Joana; Rochi, Natália; Streck, Emílio L; Quevedo, João

    2012-04-01

    Several studies have appointed for a role of glutamatergic system and/or mitochondrial function in major depression. In the present study, we evaluated the creatine kinase and mitochondrial respiratory chain activities after acute and chronic treatments with memantine (N-methyl-D: -aspartate receptor antagonist) and imipramine (tricyclic antidepressant) in rats. To this aim, rats were acutely or chronically treated for 14 days once a day with saline, memantine (5, 10 and 20 mg/kg) and imipramine (10, 20 and 30 mg/kg). After acute or chronic treatments, we evaluated mitochondrial respiratory chain complexes (I, II, II-III and IV) and creatine kinase activities in prefrontal cortex, hippocampus and striatum. Our results showed that both acute and chronic treatments with memantine or imipramine altered respiratory chain complexes and creatine kinase activities in rat brain; however, these alterations were different with relation to protocols (acute or chronic), complex, dose and brain area. Finally, these findings further support the hypothesis that the effects of imipramine and memantine could be involve mitochondrial function modulation.

  3. Weak diagnostic performance of troponin, creatine kinase and creatine kinase-MB to diagnose or exclude myocardial infarction after successful resuscitation.

    Science.gov (United States)

    Kruse, Jan M; Enghard, Philipp; Schröder, Tim; Hasper, Dietrich; Kühnle, York; Jörres, Achim; Storm, Christian

    2014-05-01

    The aim of this study is to evaluate the diagnostic accuracy of the cardiac injury markers troponin (TNT), creatine kinase (CK) and creatine kinase-MB (CK-MB) to diagnose or exclude acute myocardial infarction after cardiac arrest. 226 patients who underwent diagnostic coronary angiography after sudden cardiac arrest were analyzed retrospectively. Levels of TNT, CK and CK-MB on admission and 6h, 24h and 36 h later were retrieved from the files and compared with the results of coronary angiography. Acute myocardial infarction (AMI) as well as non-AMI patients showed increasing levels of TNT and CK after resuscitation, although the AMI group showed significantly higher TNT and CK levels. Receiver operator curves were calculated to determine the diagnostic precision of TNT, CK and CK-MB to differentiate AMI and non-AMI patients. All analyzed markers yielded mediocre diagnostic precision with an area under the ROC curve of 0.7020, 0.6802 and 0.6508 for 6h TNT, CK and CK-MB, respectively. Applying a modified cut-off of 1 μg/l the 6h TNT measurement had a sensitivity of 70.9% and specificity of 61.2% to diagnose AMI after cardiac arrest. Using CK 800 U/l as cut-off level resulted in a sensitivity of 62.5% and specificity of 73.7%, CK-MB levels higher than 100 U/l yielded a sensitivity of 58.8% and specificity of 72.7%. Cardiac injury markers cannot be used to reliably diagnose or rule out AMI after resuscitation. Consequently we propose that indication for coronary angiography should be extended to all patients without a certain alternative diagnosis explaining the occurrence of cardiac arrest. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Creatine kinase and endocrine responses of elite players pre, during, and post rugby league match play.

    Science.gov (United States)

    McLellan, Christopher P; Lovell, Dale I; Gass, Gregory C

    2010-11-01

    The purpose of the present study was to (a) examine player-movement patterns to determine total distance covered during competitive Rugby League match play using global positioning systems (GPSs) and (b) examine pre, during, and postmatch creatine kinase (CK) and endocrine responses to competitive Rugby League match play. Seventeen elite rugby league players were monitored for a single game. Player movement patterns were recorded using portable GPS units (SPI-Pro, GPSports, Canberra, Australia). Saliva and blood samples were collected 24 hours prematch, 30 minutes prematch, 30 minutes postmatch, and then at 24-hour intervals for a period of 5 days postmatch to determine plasma CK and salivary testosterone, cortisol, and testosterone:cortisol ratio (T:C). The change in the dependent variables at each sample collection time was compared to 24-hour prematch measures. Backs and forwards traveled distances 5,747 ± 1,095 and 4,774 ± 1,186 m, respectively, throughout the match. Cortisol and CK increased significantly (p < 0.05) from 30 minutes prematch to 30 minutes postmatch. Creatine kinase increased significantly (p < 0.05) postmatch, with peak CK concentration measured 24 hours postmatch (889.25 ± 238.27 U·L). Cortisol displayed a clear pattern of response with significant (p < 0.05) elevations up to 24 hours postmatch, compared with 24 hours prematch. The GPS was able to successfully provide data on player-movement patterns during competitive rugby league match play. The CK and endocrine profile identified acute muscle damage and a catabolic state associated with Rugby League match play. A return to normal T:C within 48 hours postmatch indicates that a minimum period of 48 hours is required for endocrine homeostasis postcompetition. Creatine kinase remained elevated despite 120 hours of recovery postmatch identifying that a prolonged period of at least 5 days modified activity is required to achieve full recovery after muscle damage during competitive Rugby

  5. Regenerated soleus muscle shows reduced creatine kinase efflux after contractile activity in vitro.

    Science.gov (United States)

    Baltusnikas, Juozas; Kilikevicius, Audrius; Venckunas, Tomas; Fokin, Andrej; Lionikas, Arimantas; Ratkevicius, Aivaras

    2015-02-01

    Regenerated skeletal muscles show less muscle damage after strenuous muscle exercise. The aim of the studies was to investigate if the regeneration is associated with reduced muscle creatine kinase (CK) efflux immediately after the exercise. Cryolesion was applied to the soleus muscle of 3-month-old C57BL/6J male mice. Then total CK efflux was assessed in vitro in the regenerated muscles without exercise or after 100 eccentric contractions. The same measurements were performed in the control muscles, which were not exposed to cryolesion. Regenerated muscles generated weaker (P resistance to damage after eccentric exercise.

  6. Liquid-chromatographic separation and on-line bioluminescence detection of creatine kinase isoenzymes

    Energy Technology Data Exchange (ETDEWEB)

    Bostick, W.D.; Denton, M.S.; Dinsmore, S.R.

    1980-01-01

    Isoenzymes of creatine kinase were separated by anion-exchange chromatography, with use of an elution gradient containing lithium acetate (0.1 to 0.6 mol/L). A stream splitter was used to divert a 5% side stream of column effluent, which was subsequently mixed with the reagents necessary for bioluminescence assay of the separated isoenzymes. The use of the stream splitter greatly decreased the rate of consumption of reagent and, when combined with a peristaltic pumping system, permitted independent control of the side-stream flow rate. Thus both the residence interval in a delay coil in which the ATP reaction product is formed and the bioluminescence emission was monitored in a flow-through fluorometer without use of an external light source or filters. Separation and detection of the isoenzymes of creatine kinase were rapid, sensitive, and highly selective. The incremental decrease of bioluminescence response owing to inhibition by the ions in the eluent was less than 31% across the entire gradient.

  7. Serum chemistry alterations, including creatine kinase isoenzymes, in furazolidone toxicosis of ducklings: preliminary findings.

    Science.gov (United States)

    Webb, D M; DeNicola, D B; Van Vleet, J F

    1991-01-01

    Furazolidone induces a cardiotoxicosis when fed in toxic concentrations to newly hatched ducklings. This preliminary experiment was designed to determine if creatine kinase (CK) isoenzymic activities or other serum analytes would be useful as indicators of these cardiac alterations. Sera from 12 ducklings (six fed a control ration and six fed the control ration with 700 mg furazolidone added per kg of feed [700 ppm] for 28 days) were analyzed for CK isoenzymic activities, electrolytes, nitrogenous metabolites, hepatic enzymic activities, bilirubin, and glucose. Statistically significant differences between control and treated groups were detected for creatine kinase MB (CK-MB, cardiac muscle origin) isoenzymic activity and bilirubin, potassium, calcium, and total carbon dioxide concentrations. Differences other than CK-MB isoenzymic activity were generally explained by factors related to the toxicosis or sample handling. These findings suggest that CK-MB isoenzymic activity may be useful to detect and monitor the progress of cardiac injury in furazolidone toxicosis, thereby increasing the usefulness of this model of dilated cardiomyopathy. Our findings, analyzed on the Kodak Ektachem 700 Dry Chemistry Analyzer, are compared with serum chemistry values reported in the literature.

  8. Elevated serum creatine kinase levels in psychiatric practice: differential diagnosis and clinical significance: A brief, practical guideline for clinicians.

    Science.gov (United States)

    Voros, Viktor; Osvath, Peter; Fekete, Sandor; Tenyi, Tamas

    2008-01-01

    Introduction. Elevated serum CK levels often occur in psychiatric in-patient practice. Although the majority of cases are benign and temporary, it is important to recognize and treat these conditions. Aims. To discuss the etiology, the clinical significance and the management of elevated creatine kinase levels in psychiatric in-patient practice, focusing on antipsychotic-induced rhabdomyolysis. To compare the pathogenesis and the clinical features of rhabdomyolysis and neuroleptic malignant syndrome. Methods. Review of the literature. Results. A brief, practical guideline is introduced, which may help clinicians in the differential diagnosis and in the management of patients with elevated creatine kinase activity in emergent psychiatric practice. Conclusions. The most common etiologic factors (prescription drugs, alcohol, physical reasons, cardiac etiology) and clinical syndromes (rhabdomyolysis, neuroleptic malignant syndrome, acute coronary syndrome) should be considered, when elevated creatine kinase levels are encountered in psychiatric in-patients. Routine creatine kinase measurements in asymptomatic patients on antipsychotic medications are not recommended, but patients should be carefully followed for the development of rhabdomyolysis, when muscular symptoms arise. Careful monitoring of symptoms and potential complications is critical in order to avoid devastating clinical consequences. Cautiously challenging patients with another antipsychotic after an antipsychotic-induced rhabdomyolysis is recommended to decrease the possibility of recurrence.

  9. The Effect of Direct Current Transthoracic Countershock on Human Myocardial Cells Evidenced by Creatine Kinase and Lactic Dehydrogenase Isoenzymes.

    Science.gov (United States)

    1986-05-01

    creatine kinase isoenzyme activity. In their descriptive sutdy, 11 anesthesized mongrel dogs were subjected to 10 consecutive 240 watt/second...purposes of medical/ dental study or research. C. SIGNATURES ID.yi ii .i idC-ii .prr 1. COUNSELING PHIYSICIAN /DENTIST: I have counseled this patient

  10. Early detection of skeletal muscle injury by assay of creatine kinase MM isoforms in serum after acute exercise

    DEFF Research Database (Denmark)

    Apple, F. S.; Hellsten, Ylva; Clarkson, P. M.

    1988-01-01

    We could detect skeletal muscle injury early after an acute exercise bout by measuring creatine kinase (CK, EC 2.7.3.2) MM isoforms in serum. Eleven men performed 120 alternating-arm, eccentric (muscle lengthening) biceps contractions with the intensity of each contraction being 110% of maximal...

  11. Creatine kinase BB and beta-2-microglobulin as markers of CNS metastases in patients with small-cell lung cancer

    DEFF Research Database (Denmark)

    Pedersen, A G; Bach, F W; Nissen, Mogens Holst

    1985-01-01

    Creatine kinase (CK) and its BB isoenzyme (CK-BB) were measured in CSF in 65 evaluable patients suspected of CNS metastases secondary to small-cell lung cancer (SCLC). In addition, CSF and plasma levels of beta-2-microglobulin (beta-2-m) were measured in a group of 73 evaluable patients. Of the 65...

  12. The Influence of Whole-Body Vibration on Creatine Kinase Activity and Jumping Performance in Young Basketball Players

    Science.gov (United States)

    Fachina, Rafael; da Silva, Antônio; Falcão, William; Montagner, Paulo; Borin, João; Minozzo, Fábio; Falcão, Diego; Vancini, Rodrigo; Poston, Brach; de Lira, Claudio

    2013-01-01

    Purpose: To quantify creatine kinase (CK) activity changes across time following an acute bout of whole-body vibration (WBV) and determine the association between changes in CK activity and jumping performance. Method: Twenty-six elite young basketball players were assigned to 3 groups: 36-Hz and 46-Hz vibration groups (G36 and G46, respectively)…

  13. PUTATIVE CREATINE KINASE M-ISOFORM IN HUMAN SPERM IS IDENTIFIED AS THE 70-KILODALTON HEAT SHOCK PROTEIN HSPA2

    Science.gov (United States)

    THE PUTATIVE CREATINE KINASE M-ISOFORM IN HUMAN SPERM IS IDENTIFIED AS THE 70 kDa HEAT SHOCK PROTEIN HSPA2* Gabor Huszar1, Kathryn Stone2, David Dix3 and Lynne Vigue11The Sperm Physiology Laboratory, Department of Obstetrics and Gynecology, 2 W.M. Keck Foundatio...

  14. Angiographic adverse events during percutaneous coronary intervention fail to predict creatine kinase-MB elevation.

    Science.gov (United States)

    Blankenship, James C; Islam, M Ashequl; Wood, G Craig; Iliadis, Elias A

    2004-09-01

    We attempted to determine if aggressive detection of angiographic adverse events during coronary intervention could predict subsequent creatine kinase (CK)-MB elevations. During coronary intervention, both fluoroscopy and cine angiography were used to detect angiographic adverse events. At least one angiographic adverse event occurred in 133/251 (53%) of procedures. CK-MB elevation occurred in 24% of procedures. Slow flow during the procedure (P=0.002) and chest discomfort at the end of the procedure (P=0.007) were the strongest predictors of CK-MB elevation. Among procedures with no angiographic adverse events, CK-MB elevation occurred in 15/121 (12%), accounting for 25% of CK-MB elevations. We conclude that CK-MB elevation occurs after angiographically uncomplicated coronary interventions even when angiographic adverse events are aggressively detected. Routine monitoring of cardiac enzymes is necessary to detect all patients who will experience myocardial injury after coronary intervention.

  15. Purification and partial characterization of creatine kinase from electric organ of Electrophorus electricus (L.).

    Science.gov (United States)

    Batista e Silva, C M; Nunes Tavares, N; Giovanni-De-Simone, S; Nery da Matta, A; Hassón-Voloch, A

    2000-04-01

    The present investigation deals with the purification and the partial characterization of the soluble creatine kinase (CK) isoenzyme, isolated from the electric organ electrocyte of Electrophorus electricus (L.). Purification was performed by precipitation of the enzyme in the crude extract with ammonium sulfate (80%). The precipitate obtained was analyzed on an ion exchange column of diethylaminoethyl cellulose-52 (DEAE) followed by gel filtration on Superose 12 in a Fast Protein Liquid Chromatography (FPLC) system. Electrophoretic mobility of the active peak confirmed previous results identifying the hybrid isoenzyme MB in the electrocyte cytoplasm. Electrocyte CK is a dimeric enzyme with two identical subunits of approximately 40 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The sequence analysis of the N-terminal peptide (14 amino acids) of the 40 kDa subunit showed homology with other CK enzymes from electric fish (Torpedo) and human muscle type CK.

  16. Creatine kinase and lactate dehydrogenase responses after upper-body resistance exercise with different rest intervals.

    Science.gov (United States)

    Rodrigues, Bernardo M; Dantas, Estélio; de Salles, Belmiro Freitas; Miranda, Humberto; Koch, Alexander J; Willardson, Jeffrey M; Simão, Roberto

    2010-06-01

    The purpose of the current study was to compare serum creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations at multiple time points after resistance exercise sessions that incorporated different rest intervals between sets and exercises. Twenty untrained men (18.65+/-0.49 years, 68.30+/-7.98 kg, and 174.4+/-4.80 cm) performed 2 resistance exercise sessions (i.e., 3 sets with 80% 1 repetition maximum for 5 upper-body exercises) with either 1-minute (SEQ1) or 3-minute (SEQ3) rest between sets and exercises. For each session, CK and LDH concentrations were measured before exercise (PRE) and 24, 48, and 72 hours after exercise (24P, 48P, and 72P). Subjects lifted a 24% greater (presistance exercise may invoke greater muscle damage.

  17. Creatine kinase activity in patients with diabetes mellitus type I and type II.

    Science.gov (United States)

    Jevrić-Causević, Adlija; Malenica, Maja; Dujić, Tanja

    2006-08-01

    Diabetes mellitus can be looked upon as an array of diseases, all of which exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes mellitus) is well understood, the same is not true for diabetes mellitus type II. In the latter case, relative contribution of the two factors (insulin resistance or decreased insulin secretion) varies individually, being highly increased in peripheral tissues and strictly dependant on insulin for glucose uptake. Moreover, in patients with diabetes mellitus type II, disbalance at the level of regulation of glucose metabolism as well as lipid metabolism has been noted in skeletal muscles. It is normal to assume that in this type of diabetes, these changes are reflected at the level of total activity of enzyme creatine kinase. This experimental work was performed on a group of 80 regular patients of Sarajevo General Hospital. Forty of those patients were classified as patients with diabetes type I and forty as patients with diabetes type II. Each group of patients was carefully chosen and constituted of equal number of males and females. The same was applied for adequate controls. Concentration of glucose was determined for each patient with GOD method, while activity of creatine kinase was determined with CK-NAC activated kit. Statistical analysis of the results was performed with SPSS software for Windows. Obtained results point out highly expressed differences in enzyme activity between two populations examined. Changes in enzyme activity are more expressed in patients with diabetes type II. Positive correlation between concentration of glucose and serum activity of the enzyme is seen in both categories of diabetic patients which is not the case for the patients in control group. At the same time, correlation between age and type of diabetes does exist . This is not followed at the level of enzyme activity or concentration of glucose.

  18. VDAC electronics: 3. VDAC-Creatine kinase-dependent generation of the outer membrane potential in respiring mitochondria.

    Science.gov (United States)

    Lemeshko, Victor V

    2016-07-01

    Mitochondrial energy in cardiac cells has been reported to be channeled into the cytosol through the intermembrane contact sites formed by the adenine nucleotide translocator, creatine kinase and VDAC. Computational analysis performed in this study showed a high probability of the outer membrane potential (OMP) generation coupled to such a mechanism of energy channeling in respiring mitochondria. OMPs, positive inside, calculated at elevated concentrations of creatine are high enough to restrict ATP release from mitochondria, to significantly decrease the apparent K(m,ADP) for state 3 respiration and to maintain low concentrations of Ca(2+) in the mitochondrial intermembrane space. An inhibition by creatine of Ca(2+)-induced swelling of isolated mitochondria and other protective effects of creatine reported in the literature might be explained by generated positive OMP. We suggest that VDAC-creatine kinase-dependent generation of OMP represents a novel physiological factor controlling metabolic state of mitochondria, cell energy channeling and resistance to death. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Clinical and financial impact of removing creatine kinase-MB from the routine testing menu in the emergency setting.

    Science.gov (United States)

    Le, Rachel D; Kosowsky, Joshua M; Landman, Adam B; Bixho, Ida; Melanson, Stacy E F; Tanasijevic, Milenko J

    2015-01-01

    Cardiac troponins T and I have replaced creatine kinase-MB (CK-MB) as the criterion standard for diagnosing myocardial injury. However, many laboratories still routinely perform a high volume of CK-MB testing in conjunction with troponin. The purpose of this study is to study the clinical and financial impact of removing CK-MB from the routine emergency department (ED) test menu at a large academic medical center. Creatine kinase-MB was removed from ED ordering templates and laboratory requisitions (ie, intervention), although the test could still be manually ordered. Data for creatine kinase (CK), CK-MB, and troponin T (TnT) specimens ordered during a 12-month period (6 months preintervention and 6 months postintervention) (n = 14571) was downloaded from our laboratory information system. All specimens with (1) normal TnT (ie, 6.6 ng/mL), and (3) elevated CK-MB index (ie, >5) were considered discrepant and independently reviewed by 2 ED clinicians for the presence of an acute coronary syndrome and for documentation of final diagnosis. Creatine kinase, CK-MB, and TnT ED volumes preintervention and postintervention were analyzed to assess laboratory cost savings. Of the 6444 cases included in the analysis, only 17 were discrepant. Of all 17 cases, no patients were diagnosed with acute coronary syndrome. After removing CK-MB from the templates and requisitions, CK-MB and CK volumes decreased by 80% and 76%, respectively, translating to annual reagent cost savings of approximately $47000. Creatine kinase-MB can be removed from the routine ED test menu without adversely affecting patient care. In addition, substantial cost savings can be achieved by reducing unnecessary CK-MB testing and associated CK orders. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Inhibition of brain creatine kinase activity after renal ischemia is attenuated by N-acetylcysteine and deferoxamine administration.

    Science.gov (United States)

    Di-Pietro, Priscila B; Dias, Márcia L; Scaini, Giselli; Burigo, Márcio; Constantino, Larissa; Machado, Roberta A; Dal-Pizzol, Felipe; Streck, Emilio L

    2008-03-21

    Encephalopathy may accompany acute or chronic renal failure, and the mechanisms responsible for neurological complications in patients with renal failure are poorly known. Considering that creatine kinase (CK) is important for brain energy homeostasis and is inhibited by free radicals, and that oxidative stress is probably involved in the pathogenesis of uremic encephalopathy, we measured CK activity (hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex) in brain if rats submitted to renal ischemia and the effect of administration of antioxidants (N-acetylcysteine, NAC and deferoxamine, DFX) on this enzyme. We verified that CK activity was not altered in cerebellum and striatum of rats. CK activity was inhibited in prefrontal cortex and hippocampus of rats 12h after renal ischemia. The treatment with antioxidants prevented such effect. Cerebral cortex was also affected, but in this area CK activity was inhibited 6 and 12h after renal ischemia. Moreover, only NAC or NAC plus DFX were able to prevent the inhibition on the enzyme. Although it is difficult to extrapolate our findings to the human condition, the inhibition of brain CK activity after renal failure may be associated to neuronal loss and may be involved in the pathogenesis of uremic encephalopathy.

  1. Peroxidase-coupled method for kinetic colorimetry of total creatine kinase activity in serum.

    Science.gov (United States)

    Wimmer, M C; Artiss, J D; Zak, B

    1985-10-01

    We describe a peroxidase-coupled method involving a colorimetric indicator reaction for determining the total activity of creatine kinase (EC 2.7.3.2) in serum. The kinetically favorable reverse reaction is exploited to generate adenosine 5'-triphosphate, which is used in the glycerol kinase-catalyzed phosphorylation of glycerol. The glycerol 3-phosphate so generated is oxidized in the presence of alpha-glycerophosphate oxidase to produce hydrogen peroxide, which is reduced in the presence of peroxidase with the simultaneous oxidation and coupling of 4-aminoantipyrene and 2-hydroxy-3,5-dichlorobenzenesulfonate to produce an intensely colored red chromogen. Results of the proposed method (y) correlate well with those of the Boehringer-Mannheim "CK-NAC UV" method as applied to the Hitachi 705 chemistry analyzer (y = 1.025 chi - 18.1, r = 0.9985, n = 100, range = 19-4531 U/L). The sensitivity of the method, based on molar absorptivities, is nearly fourfold that of procedures involving the reduction of NADP+.

  2. Fatigue resistance of rat extraocular muscles does not depend on creatine kinase activity.

    Science.gov (United States)

    McMullen, Colleen A; Hayess, Katrin; Andrade, Francisco H

    2005-08-17

    Creatine kinase (CK) links phosphocreatine, an energy storage system, to cellular ATPases. CK activity serves as a temporal and spatial buffer for ATP content, particularly in fast-twitch skeletal muscles. The extraocular muscles are notoriously fast and active, suggesting the need for efficient ATP buffering. This study tested the hypotheses that (1) CK isoform expression and activity in rat extraocular muscles would be higher, and (2) the resistance of these muscles to fatigue would depend on CK activity. We found that mRNA and protein levels for cytosolic and mitochondrial CK isoforms were lower in the extraocular muscles than in extensor digitorum longus (EDL). Total CK activity was correspondingly decreased in the extraocular muscles. Moreover, cytoskeletal components of the sarcomeric M line, where a fraction of CK activity is found, were downregulated in the extraocular muscles as was shown by immunocytochemistry and western blotting. CK inhibition significantly accelerated the development of fatigue in EDL muscle bundles, but had no major effect on the extraocular muscles. Searching for alternative ATP buffers that could compensate for the relative lack of CK in extraocular muscles, we determined that mRNAs for two adenylate kinase (AK) isoforms were expressed at higher levels in these muscles. Total AK activity was similar in EDL and extraocular muscles. These data indicate that the characteristic fatigue resistance of the extraocular muscles does not depend on CK activity.

  3. Fatigue resistance of rat extraocular muscles does not depend on creatine kinase activity

    Directory of Open Access Journals (Sweden)

    Hayeß Katrin

    2005-08-01

    Full Text Available Abstract Background Creatine kinase (CK links phosphocreatine, an energy storage system, to cellular ATPases. CK activity serves as a temporal and spatial buffer for ATP content, particularly in fast-twitch skeletal muscles. The extraocular muscles are notoriously fast and active, suggesting the need for efficient ATP buffering. This study tested the hypotheses that (1 CK isoform expression and activity in rat extraocular muscles would be higher, and (2 the resistance of these muscles to fatigue would depend on CK activity. Results We found that mRNA and protein levels for cytosolic and mitochondrial CK isoforms were lower in the extraocular muscles than in extensor digitorum longus (EDL. Total CK activity was correspondingly decreased in the extraocular muscles. Moreover, cytoskeletal components of the sarcomeric M line, where a fraction of CK activity is found, were downregulated in the extraocular muscles as was shown by immunocytochemistry and western blotting. CK inhibition significantly accelerated the development of fatigue in EDL muscle bundles, but had no major effect on the extraocular muscles. Searching for alternative ATP buffers that could compensate for the relative lack of CK in extraocular muscles, we determined that mRNAs for two adenylate kinase (AK isoforms were expressed at higher levels in these muscles. Total AK activity was similar in EDL and extraocular muscles. Conclusion These data indicate that the characteristic fatigue resistance of the extraocular muscles does not depend on CK activity.

  4. Mitochondrial creatine kinase activity and phosphate shuttling are acutely regulated by exercise in human skeletal muscle.

    Science.gov (United States)

    Perry, Christopher G R; Kane, Daniel A; Herbst, Eric A F; Mukai, Kazutaka; Lark, Daniel S; Wright, David C; Heigenhauser, George J F; Neufer, P Darrell; Spriet, Lawrence L; Holloway, Graham P

    2012-11-01

    Energy transfer between mitochondrial and cytosolic compartments is predominantly achieved by creatine-dependent phosphate shuttling (PCr/Cr) involving mitochondrial creatine kinase (miCK). However, ADP/ATP diffusion through adenine nucleotide translocase (ANT) and voltage-dependent anion carriers (VDACs) is also involved in this process. To determine if exercise alters the regulation of this system, ADP-stimulated mitochondrial respiratory kinetics were assessed in permeabilized muscle fibre bundles (PmFBs) taken from biopsies before and after 2 h of cycling exercise (60% ) in nine lean males. Concentrations of creatine (Cr) and phosphocreatine (PCr) as well as the contractile state of PmFBs were manipulated in situ. In the absence of contractile signals (relaxed PmFBs) and miCK activity (no Cr), post-exercise respiratory sensitivity to ADP was reduced in situ (up to 126% higher apparent K(m) to ADP) suggesting inhibition of ADP/ATP diffusion between matrix and cytosolic compartments (possibly ANT and VDACs). However this effect was masked in the presence of saturating Cr (no effect of exercise on ADP sensitivity). Given that the role of ANT is thought to be independent of Cr, these findings suggest ADP/ATP, but not PCr/Cr, cycling through the outer mitochondrial membrane (VDACs) may be attenuated in resting muscle after exercise. In contrast, in contracted PmFBs, post-exercise respiratory sensitivity to ADP increased with miCK activation (saturating Cr; 33% lower apparent K(m) to ADP), suggesting prior exercise increases miCK sensitivity in situ. These observations demonstrate that exercise increases miCK-dependent respiratory sensitivity to ADP, promoting mitochondrial-cytosolic energy exchange via PCr/Cr cycling, possibly through VDACs. This effect may mask an underlying inhibition of Cr-independent ADP/ATP diffusion. This enhanced regulation of miCK-dependent phosphate shuttling may improve energy homeostasis through more efficient coupling of oxidative

  5. The influence of individualizing physical loads on speed, creatine kinase activity and lactate dehydrogenase in football players.

    Directory of Open Access Journals (Sweden)

    2008-06-01

    Full Text Available Introduction: One of the most important training problems in: contemporary football is speed preparation of a player for the season and the ability of keeping it on the same, relatively high level throughout the starting period [1]. The main process used for re-synthesis ATP during single, short-lasting efforts of maximal intensity, is decomposition of phospho-creatine under the influence of creatine kinase enzyme. Physical loads imposed during speed trainings often exceed the possibility of producing energy from phosphogenic reserve through oxygen - lactate free processes, because the supply of phospho-creatine is used very quickly. In such circumstances the lacking energy is refilled through processes called oxygen free glicolise with the help of lactate dehydrogenase enzyme. The aim of the work was to answer the question:

  6. Identification of high responders for interleukin-6 and creatine kinase following acute eccentric resistance exercise in elderly obese women.

    Science.gov (United States)

    Tajra, Vitor; Tibana, Ramires Alsamir; Vieira, Denis Cesar Leite; de Farias, Darlan Lopes; Teixeira, Tatiane Gomes; Funghetto, Silvana Schwerz; Silva, Alessandro Oliveira; de Sousa, Nuno Manuel Frade; Willardson, Jeffrey; Karnikowski, Margô Gomes Oliveira; Prestes, Jonato

    2014-11-01

    Resistance exercise is used as a non-pharmacological tool to elicit both gains in and maintenance of physical function in the elderly. Thus, the present study examined the acute response of creatine kinase and interleukin-6 following an eccentric resistance exercise session in elderly obese women classified as high responders or normal responders. Cross-sectional field study. Ninety elderly obese women (69.4 ± 6.01 years) were tested for a 10 repetition maximum on the leg extension exercise and then completed an acute eccentric resistance exercise session consisting of seven sets of 10 repetitions at 110% of 10 repetition maximum with a rest of 3 min between sets. Subjects were divided into normal response or high response on the basis of the peak serum interleukin-6 (NR = 59 and HR = 7) and creatine kinase (NR = 81 and HR = 9) concentration being greater than (HR) or less than (NR) the 90th percentile. Creatine kinase was higher at 0 h, 3h, 24h and 48 h following the ERE for the HR group. The peak creatine kinase was significantly higher in HR group versus the normal response group. The average increase in the serum interleukin-6 Δ for the HR group (∼ 850%) was significantly higher versus the normal response group (∼ 55%). Serum interleukin-6 was significantly higher at 0 h and 24h following eccentric resistance exercise only for the high response group, while peak levels were significantly higher in high response group versus the normal response group (p ≤ 0.005). Only one subject met the criteria to be classified as high response for both creatine kinase and interleukin-6 responsiveness. Elderly individuals classified as high response experienced greater creatine kinase and interleukin-6 responses to ERE. Thus, a prudent approach for eccentric resistance exercise prescription might be programming additional recovery days and/or lower intensity training, especially in the beginning stages of a program. Copyright © 2013 Sports Medicine Australia

  7. Evaluation of total creatine kinase levels in a spectrum of neuro-psychiatric disorders in a tertiary neurosciences centre

    OpenAIRE

    Anshu Gupta; Chhavi Gupta; Sarabjeet Khurana

    2015-01-01

    Introduction: To study usefulness of total creatine kinase (CK) as a screening tool in various neurological and psychiatric disorders in emergency setting of a tertiary care hospital. Materials and Methods: A 1-year retrospective study was conducted on 102 patients with complaints pertaining to neurological and psychiatric disorders in a tertiary neurosciences centre in a metropolitan city. Blood samples in plain vial were received in Emergency Laboratory and total CK levels were measured by ...

  8. Comparison of serum cardiac troponin-I and creatine kinase MB isoenzyme concentrations in asphyxiated neonates

    Institute of Scientific and Technical Information of China (English)

    Nouran F.Hussien; Eman A.Abdel Ghany; Amany E.Elwan; Yasser H.Kamel; Dina K.Ali

    2009-01-01

    Objective:To assess the correlation of signs of myocardial damage to serum cardiac tmponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significanfly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in selMnl CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.

  9. Muscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response.

    Science.gov (United States)

    Hody, S; Rogister, B; Leprince, P; Wang, F; Croisier, J-L

    2013-08-01

    Unaccustomed eccentric exercise may cause skeletal muscle damage with an increase in plasma creatine kinase (CK) activity. Although the wide variability among individuals in CK response to standardized lengthening contractions has been well described, the reasons underlying this phenomenon have not yet been understood. Therefore, this study investigated a possible correlation of the changes in muscle damage indirect markers after an eccentric exercise with the decline in muscle performance during the exercise. Twenty-seven healthy untrained male subjects performed three sets of 30 maximal isokinetic eccentric contractions of the knee extensors. The muscular work was recorded using an isokinetic dynamometer to assess muscle fatigue by means of various fatigue indices. Plasma CK activity, muscle soreness, and stiffness were measured before (pre) and one day after (post) exercise. The eccentric exercise bout induced significant changes of the three muscle damage indirect markers. Large inter-subject variability was observed for all criteria measured. More interestingly, the log (CK(post) /CK(pre)) and muscle stiffness appeared to be closely correlated with the relative work decrease (r = 0.84, r(2)  = 0.70 and r = 0.75, r(2)  = 0.56, respectively). This is the first study to propose that the muscle fatigue profile during maximal eccentric protocol could predict the magnitude of the symptoms associated with muscle damage in humans.

  10. Creatine kinase isoenzyme patterns upon chronic exposure to cigarette smoke: protective effect of Bacoside A.

    Science.gov (United States)

    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2005-01-01

    Cigarette smoking is implicated as a major risk factor in the development of cardiovascular and cerebrovascular diseases. Creatine kinase (CK) and its isoforms (CK-MM, MB, BB) have been advocated as sensitive markers in the assessment of cardiac and cerebral damage. Therefore, in the present study, we report the isoenzyme patterns of CK in rats upon exposure to cigarette smoke and the protective effect of Bacoside A against chronic smoking induced toxicity. Adult male albino rats were exposed to cigarette smoke and simultaneously administered with Bacoside A, the active constituent from the plant Bacopa monniera, for a period of 12 weeks. The activity of CK was assayed in serum, heart and brain, and its isoenzymes in serum were separated electrophoretically. Rats exposed to cigarette smoke showed significant increase in serum CK activity with concomitant decrease in heart and brain. Also cigarette smoke exposure resulted in a marked increase in all the three isoforms in serum. Administration of Bacoside A prevented these alterations induced by cigarette smoking. Cigarette smoking is known to cause free radical mediated lipid peroxidation leading to increased membrane permeability and cellular damage in the heart and brain resulting in the release of CK into the circulation. The protective effect of Bacoside A on the structural and functional integrity of the membrane prevented the leakage of CK from the respective tissues, which could be attributed to its free radical scavenging and anti-lipid peroxidative effect.

  11. Creatine kinase B subunit as measured with a radioimmunoassay kit in detection of acute myocardial infarction.

    Science.gov (United States)

    Witherspoon, L R; Shuler, S E; Genre, C F; Gilbert, S S; Moore, R J; Meihaus, V; Hurry, E K

    1983-02-01

    Results with a commercial radioimmunoassay (RIA) reagent kit for quantification of the creatine kinase B subunit (CK-B) (Nuclear-Medical Laboratories, Irving, TX 75061) were compared with results obtained by electrophoresis for patients consecutively admitted to our coronary care unit for suspected acute myocardial infarction. Analytical sensitivity, precision, and specificity of the RIA were satisfactory. Its clinical efficacy was assessed in 97 patients suspected of having had an acute myocardial infarction. Of 30 patients who had had an acute myocardial infarction, increased CK-B was detected by RIA in 30 and by electrophoresis in 27. The temporal relationship between CK-B by RIA and CK-MB by electrophoresis was similar. Of 66 admissions where infarction was not established, CK-B was negligibly increased in samples from four patients by RIA, and from one by electrophoresis. Although not abnormally increased (greater than 5 U/L), CK-MB was detected by electrophoresis in samples from another five of these 66 patients. We conclude that estimation of CK-B by this RIA is an excellent alternative to estimation of CK-MB by electrophoresis in patients suspected of having had an acute myocardial infarction.

  12. A rare case of neuroleptic malignant syndrome without elevated serum creatine kinase.

    Science.gov (United States)

    Nisijima, Koichi; Shioda, Katutoshi

    2014-01-01

    Neuroleptic malignant syndrome (NMS) is a life-threatening adverse reaction to antipsychotic drugs. Although there is no specific examination able to diagnose NMS, serum creatine kinase (CK) elevation has been reported in over 90% of NMS patients. In this report, we describe a patient who developed NMS but had normal CK levels. The patient presented with hyperthermia of over 38°C, severe muscle rigidity, autonomic dysfunction, and altered mental status. Although serum CK levels were measured three times during the course of NMS, the levels were within the normal range. The patient died of respiratory failure 13 days after the onset of NMS symptoms. As patients without elevated serum CK levels are rarely reported, we discuss potential reasons why the serum CK was not elevated in our patient. This case shows clinicians that although serum CK elevation is a useful indicator for the early detection of NMS, the diagnosis of NMS must be determined by clinical symptoms as otherwise, the appropriate treatment procedures for NMS may be delayed.

  13. A rare case of neuroleptic malignant syndrome without elevated serum creatine kinase

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    Nisijima K

    2014-02-01

    Full Text Available Koichi Nisijima, Katutoshi Shioda Department of Psychiatry, Jichi Medical University, Tochigi, Japan Abstract: Neuroleptic malignant syndrome (NMS is a life-threatening adverse reaction to antipsychotic drugs. Although there is no specific examination able to diagnose NMS, serum creatine kinase (CK elevation has been reported in over 90% of NMS patients. In this report, we describe a patient who developed NMS but had normal CK levels. The patient presented with hyperthermia of over 38°C, severe muscle rigidity, autonomic dysfunction, and altered mental status. Although serum CK levels were measured three times during the course of NMS, the levels were within the normal range. The patient died of respiratory failure 13 days after the onset of NMS symptoms. As patients without elevated serum CK levels are rarely reported, we discuss potential reasons why the serum CK was not elevated in our patient. This case shows clinicians that although serum CK elevation is a useful indicator for the early detection of NMS, the diagnosis of NMS must be determined by clinical symptoms as otherwise, the appropriate treatment procedures for NMS may be delayed. Keywords: malnutrition, NMS, CK, hyperthermia

  14. The Effect of Creatine Kinase Inhibition on Contractile Properties of Human Resistance Arteries.

    Science.gov (United States)

    Taherzadeh, Zhila; Karamat, Fares A; Ankum, Willem M; Clark, Joseph F; van Montfrans, Gert A; van Bavel, Ed; Brewster, Lizzy M

    2016-02-01

    Creatine kinase (CK) is a main predictor of blood pressure, and this is thought to largely depend on high resistance artery contractility. We previously reported an association between vascular contractility and CK in normotensive pregnancy, but pregnancy is a strong CK inducer, and data on human hypertension are lacking. Therefore, we further explored CK-dependency of vascular contractility outside the context of pregnancy in normotensive and hypertensive women. Nineteen consecutive women, mean age 42 years (SE 1.3), mean systolic/diastolic blood pressure respectively 142.6 (SE 5.9)/85.6 (3.4) mm Hg (9 hypertensive), donated an omental fat sample during abdominal surgery. We compared vasodilation after the specific CK inhibitor 2,4-dinitro-1-fluorobenzene (DNFB; 10(-6) mol/l) to sodium nitroprusside (10(-6) mol/l) in isolated resistance arteries using a wire myograph. Additionally, we assessed predictors of vasoconstrictive force. DNFB reduced vascular contractility to 24.3% (SE 4.4), P resistance artery contractility across human normotension and primary hypertension outside the context of pregnancy. Further studies should explore the effect of CK inhibitors on clinical blood pressure. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Increased resistance to fatigue in creatine kinase deficient muscle is not due to improved contractile economy.

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    ter Veld, Frank; Nicolay, Klaas; Jeneson, Jeroen A L

    2006-06-01

    There has been speculation on the origin of the increased endurance of skeletal muscles in creatine kinase (CK)-deficient mice. Important factors that have been raised include the documented increased mitochondrial capacity and alterations in myosin heavy chain (MyHC) isoform composition in CK-deficient muscle. More recently, the absence of inorganic phosphate release from phosphocreatine hydrolysis in exercising CK-deficient muscle has been postulated to contribute to the lower fatigueability in skeletal muscle. In this study, we tested the hypothesis that the reported shift in MyHC composition to slower isoforms in CK-deficient muscle leads to a decrease in oxygen cost of twitch performance. To that aim, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated from wild-type (WT) and knock-out mice deficient in the cytoplasmic muscle-type and sarcomeric mitochondrial isoenzymes of CK, and oxygen consumption per twitch time-tension-integral (TTI) was measured. The results show that the adaptive response to loss of CK function does not involve any major change to contractile economy of skeletal muscle.

  16. From energy store to energy flux: a study in creatine kinase-deficient fast skeletal muscle.

    Science.gov (United States)

    Kaasik, Allen; Veksler, Vladimir; Boehm, Ernest; Novotova, Marta; Ventura-Clapier, Renée

    2003-04-01

    Fast-twitch skeletal muscle of mice deficient in cytosolic and mitochondrial creatine kinase isoforms (CK-/-) lack burst activity but can sustain prolonged contractile activity, suggesting that adaptive mechanisms can regulate local adenine nucleotide turnover. We investigated whether direct energy and signal channeling between mitochondria and sarcoplasmic reticulum (SR) or myofilaments may exist that compensate for the lack of CK isoenzymes. Oxidative capacity of fast-twitch muscle was increased twofold in CK-/- mice. Energy cross talk between organelles was studied in muscle fibers with permeabilized sarcolemma. Energy supply to SR was estimated by analyzing the tension transient induced by caffeine and energy supply to myofilaments was estimated by the relaxation of rigor tension, both under different conditions of energy supply. In normal mice, ATP directly produced by mitochondria was not able to sustain calcium uptake and to relax rigor tension as efficiently as ATP produced by bound CK. However, in CK-/- mice, mitochondria ability to provide ATP for calcium uptake and relaxation of rigor tension was dramatically enhanced, suggesting a direct ATP/ADP channeling between sites of energy production mitochondria) and energy utilization in CK-/- mice. These results demonstrate two possible patterns of energy transport in muscle cells: energy store with phosphocreatine and energy flux through mitochondria.

  17. Inhibition of creatine kinase activity from rat cerebral cortex by D-2-hydroxyglutaric acid in vitro.

    Science.gov (United States)

    da Silva, Cleide G; Bueno, Ana Rúbia F; Schuck, Patrícia F; Leipnitz, Guilhian; Ribeiro, César A J; Rosa, Rafael B; Dutra Filho, Carlos S; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir

    2004-01-01

    D-2-Hydroxyglutaric acid (DGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as D-2-hydroxyglutaric aciduria (DHGA). Although this disease is predominantly characterized by severe neurological findings, the underlying mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of DGA on total, cytosolic, and mitochondrial creatine kinase (CK) activities from cerebral cortex of 30-day-old Wistar rats. Total CK activity (tCK) was measured in whole cell homogenates, whereas cytosolic and mitochondrial activities were measured in the cytosolic and mitochondrial preparations from cerebral cortex. We verified that CK activities were significantly inhibited by DGA (11-34% inhibition) at concentrations as low as 0.25 mM, being the mitochondrial fraction the most affected activity. Kinetic studies revealed that the inhibitory effect of DGA was non-competitive in relation to phosphocreatine. We also observed that this inhibition was fully prevented by pre-incubation of the homogenates with reduced glutathione, suggesting that the inhibitory effect of DGA on tCK activity is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of CK activity for brain metabolism homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA may be related to the neurodegeneration of patients affected by DHGA.

  18. Delirium and High Creatine Kinase and Myoglobin Levels Related to Synthetic Cannabinoid Withdrawal

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    Ahmet Bulent Yazici

    2017-01-01

    Full Text Available Synthetic cannabinoids (SCs are included in a group of drugs called new psychoactive substances. Effects of SCs on the central nervous system are similar to other cannabinoids, but 2–100 times more potent than marijuana. Thus, addiction and withdrawal symptoms are more severe than natural cannabinoids. Withdrawal symptoms of SCs were reported in the literature previously. But there is no report about SC withdrawal delirium and its treatment. Several studies reported that agonists of CB1 receptors play a role in GABA and glutamatergic neurotransmission, which is similar to the effects of alcohol on GABA and glutamatergic receptors. Previous studies on alcohol delirium cases suggested that elevated creatine kinase (CK can be a marker of progress. This study reports delirium and high serum CK levels related to SC withdrawal and offers a treatment with benzodiazepine for them. We described two cases treated in our inpatient clinic about SC withdrawal with increase of serum CK level and other laboratory parameters. One of them demonstrated delirium symptoms and the other did not with early rapid treatment.

  19. American ginseng supplementation attenuates creatine kinase level induced by submaximal exercise in human beings

    Institute of Scientific and Technical Information of China (English)

    Cheng-Chen Hsu; Min-Chen Ho; Li-Chin Lin; Borcherng Su; Mei-Chich Hsu

    2005-01-01

    AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance.METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo)and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk.They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover,the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise,immediately after exercise, and 20, 40, 60, and 120 min after exercise.RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen.CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.

  20. Molecular Characterization and Expression Analysis of Creatine Kinase Muscle ( Gene in Horse

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    Kyong-Tak Do

    2015-12-01

    Full Text Available Since ancient days, domestic horses have been closely associated with human civilization. Today, horse racing is an important industry. Various genes involved in energy production and muscle contraction are differentially regulated during a race. Among them, creatine kinase (CK is well known for its regulation of energy preservation in animal cells. CK is an iso-enzyme, encoded by different genes and expressed in skeletal muscle, heart, brain and leucocytes. We confirmed that the expression of CK-M significantly increased in the blood after a 30 minute exercise period, while no considerable change was observed in skeletal muscle. Analysis of various tissues showed an ubiquitous expression of the CK-M gene in the horse; CK-M mRNA expression was predominant in the skeletal muscle and the cardiac muscle compared to other tissues. An evolutionary study by synonymous and non-synonymous single nucleotide polymorphism ratio of CK-M gene revealed a positive selection that was conserved in the horse. More studies are warranted in order to develop the expression of CK-M gene as a biomarker in blood of thoroughbred horses.

  1. Individual analysis of creatine kinase concentration in Brazilian elite soccer players

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    Adriano Lima Alves

    2015-04-01

    Full Text Available OBJECTIVE: to determine the individual profile of blood concentration of creatine kinase CK in elite soccer players as well as to analyze the CK concentrations in different periods during the Professional Brazilian Championship. METHODS: resting CK of 17 soccer players was evaluated before the competition pre-season and after the matches 36 and 46 hours after the games CKGame for the individual blood CK. The Chi-square test was used to analyze the individual CK during the season. The competitive season was divided into three periods: initial, intermediate and final. The one-way ANOVA with repeated measurements followed by post hoc Student-Newman-Keuls test was used to compare the individual CK of each soccer player in each competitive period. The significance level was set at p<0.05. RESULTS: the highest frequency of individual CK was found in the second quartile 71 observations and the lowest frequency in the first 26 observations and the fourth quartile 40 observations compared to the expected number of 45.8 x2=22.21. CK concentrations were lower in the intermediate mean=66.99% and final mean=60.21% periods than in the initial period mean=89.33%. CONCLUSION: soccer players did not show elevated muscle damage and probably a muscle adaptation occurred in the competition, due to the reduction of CK concentrations observed.

  2. Local ATP generation by brain-type creatine kinase (CK-B facilitates cell motility.

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    Jan W P Kuiper

    Full Text Available BACKGROUND: Creatine Kinases (CK catalyze the reversible transfer of high-energy phosphate groups between ATP and phosphocreatine, thereby playing a storage and distribution role in cellular energetics. Brain-type CK (CK-B deficiency is coupled to loss of function in neural cell circuits, altered bone-remodeling by osteoclasts and complement-mediated phagocytotic activity of macrophages, processes sharing dependency on actomyosin dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide evidence for direct coupling between CK-B and actomyosin activities in cortical microdomains of astrocytes and fibroblasts during spreading and migration. CK-B transiently accumulates in membrane ruffles and ablation of CK-B activity affects spreading and migration performance. Complementation experiments in CK-B-deficient fibroblasts, using new strategies to force protein relocalization from cytosol to cortical sites at membranes, confirmed the contribution of compartmentalized CK-B to cell morphogenetic dynamics. CONCLUSION/SIGNIFICANCE: Our results provide evidence that local cytoskeletal dynamics during cell motility is coupled to on-site availability of ATP generated by CK-B.

  3. Relationship of creatine kinase to body composition, disease state, and longevity in ALS.

    Science.gov (United States)

    Gibson, Summer B; Kasarskis, Edward J; Hu, Nan; Pulst, Stefan-M; Mendiondo, Marta S; Matthews, Dwight E; Mitsumoto, Hiroshi; Tandan, Rup; Simmons, Zachary; Kryscio, Richard J; Bromberg, Mark B

    2015-01-01

    Our objective was to explore if creatine kinase (CK) levels correlate with survival in amyotrophic lateral sclerosis (ALS), and whether a correlation is independent of other well-studied predictors such as location of onset, gender, age, fat free mass, spasticity, cramps, and fasciculations. We analyzed data from 80 ALS patients from a 48-week non-interventional longitudinal multicenter nutrition study with long term follow-up. The overall mean CK was 214 ± 191.8 U/l (range 22-1992 U/l). Forty-five percent of patients had at least one high CK value (> 200 U/l), and about half maintained a high CK value, but there was no trend over the study period. Male gender and extremity onset were significantly associated with high CK. In univariate analysis, age, bioelectric impedance spectroscopy (BIS) fat free mass, spasticity, and fasciculations were not associated with CK level. There was an association between CK and muscle cramps (p < 0.001). In survival analysis, low CK (≤ 200 U/l) was associated with a longer overall survival (p = 0.02), when adjusting for location of onset, age, race, gender, BIS fat free mass, and study site. In conclusion, CK may be a useful marker for ALS survival, which has implications for clinical care and the design of future clinical trials.

  4. Comparison of the inhibitory effects of mercury and cadmium on the creatine kinase from Electrophorus electricus (L).

    Science.gov (United States)

    Araujo, G M; Silva, C B; Hasson-Voloch, A

    1996-04-01

    We have determined the effects of mercury and cadmium on the creatine kinase activity of the electric organ of Electrophorus electricus (L.) which catalyses the transphosphorylation reaction between phosphocreatine and magnesium adenosine-5'-di-phosphate and has essential sulfhydryl groups. The kinetic effects of these heavy metals, which have high affinity for sulfhydryl groups, on the creatine kinase activity were analysed with the three reaction components: phosphocreatine, adenosine-5'-di-phosphate and magnesium. The kinetic data were analysed with a non-linear regression program (Sigmaplot for Windows). Both metals inhibit creatine kinase activity in the micromolar range, mercury being a more potent inhibitor than cadmium. With phosphocreatine as substrate, mercury behaved as a mixed partial hyperbolic inhibitor, non-competitive inhibitor with adenosine-5'-di-phosphate, and with magnesium mercury behaved as a competitive inhibitor. Cadmium inhibition was shown to be of a classical competitive nature with respect to both substrates, phosphocreatine or adenosine-5'-di-phosphate, and non-competitive when magnesium was the variable in the reaction mixture. The results suggest that the binding site of mercury is at or near the phosphocreatine site, but it is not the same as adenosine-5'-di-phosphate, whereas cadmium competes with these substrates to bind at the same sulphydryl site.

  5. Serum creatine kinase and CK-MB isoenzyme responses to acute and prolonged swimming in trained athletes.

    Science.gov (United States)

    Symanski, J D; McMurray, R G; Silverman, L M; Smith, B W; Siegel, A J

    1983-04-01

    Six highly-trained male swimmers completed a maximum work capacity tethered swim and a 1-h continuous tethered swim at approximately 70% VO2max in order to evaluate total serum creatine kinase and CK-MB isoenzyme changes. Venous blood obtained before, 5 min post-, 6 h post-, and 24 h post-exercise was analyzed for total serum CK (kinetic UV method, normal = less than 100 U/l) and CK-MB isoenzyme (quantitative electrophoretic technique, normal = less than 5 U/l). VO2max averaged 4.59 +/- 0.28 l/min, with a mean total work time of 24.5 min to achieve maximum capacity. Mean resting total CK was 100.5 +/- 15.8 U/l. Compared to rest, neither swim bout produced a significant (p greater than 0.05) elevation in mean total creatine kinase. No CK-MB isoenzyme was observed in any post-exercise blood sample. Swimming, performed by highly-trained swimmers at high levels of intensity or for prolonged durations, may not impose sufficient degrees of trauma producing muscular stress. Therefore, the structural integrity of the cell membrane is maintained and the loss of intracellular creatine kinase to the bloodstream prevented.

  6. Effect of physical exercise on changes in activities of creatine kinase, cytochrome c oxidase and ATP levels caused by ovariectomy.

    Science.gov (United States)

    Siebert, Cassiana; Kolling, Janaína; Scherer, Emilene B S; Schmitz, Felipe; da Cunha, Maira Jaqueline; Mackedanz, Vanize; de Andrade, Rodrigo B; Wannmacher, Clovis M D; Wyse, Angela T S

    2014-09-01

    The reduction in the secretion of ovarian hormones, principally estrogen, is a consequence of menopause. Estrogens act primarily as female sex hormones, but also exert effects on different physiological systems including the central nervous system. The treatment normally used to reduce the symptoms of menopause is the hormone therapy, which seems to be effective in treating symptoms, but it may be responsible for adverse effects. Based on this, there is an increasing demand for alternative therapies that minimize signs and symptoms of menopause. In the present study we investigated the effect of ovariectomy and/or physical exercise on the activities of energy metabolism enzymes, such as creatine kinase (cytosolic and mitochondrial fractions), pyruvate kinase, succinate dehydrogenase, complex II, cytochrome c oxidase, as well as on ATP levels in the hippocampus of adult rats. Adult female Wistar rats with 90 days of age were subjected to ovariectomy (an animal model widely used to mimic the postmenopausal changes). Thirty days after the procedure, the rats were submitted to the exercise protocol, which was performed three times a week for 30 days. Twelve hours after the last training session, the rats were decapitated for subsequent biochemical analyzes. Results showed that ovariectomy did not affect the activities of pyruvate kinase, succinate dehydrogenase and complex II, but decreased the activities of creatine kinase (cytosolic and mitochondrial fractions) and cytochrome c oxidase. ATP levels were also reduced. Exercise did not produce the expected results since it was only able to partially reverse the activity of creatine kinase cytosolic fraction. The results of this study suggest that estrogen deficiency, which occurs as a result of ovariectomy, affects generation systems and energy homeostasis, reducing ATP levels in hippocampus of adult female rats.

  7. Low Serum Creatine Kinase Level Predicts Mortality in Patients with a Chronic Kidney Disease.

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    Adrien Flahault

    Full Text Available Serum creatine kinase (sCK reflects CK activity from striated skeletal muscle. Muscle wasting is a risk factor for mortality in patients with chronic kidney disease (CKD. The aim of this study is to evaluate whether sCK is a predictor of mortality and end-stage renal disease (ESRD in a CKD population.We included 1801 non-dialysis-dependent CKD patients from the NephroTest cohort. We used time-fixed and time-dependent cause-specific Cox models to estimate hazard ratios (HRs for the risk of death and for the risk of ESRD associated with gender-specific sCK tertiles.Higher sCK level at baseline was associated with a lower age, a higher body mass index, and a higher level of 24 h urinary creatinine excretion, serum albumin and prealbumin (p<0.001. Men, patients of sub-Saharan ancestry, smokers and statin users also experienced a higher level of sCK. In a time-fixed Cox survival model (median follow-up 6.0 years, the lowest gender-specific sCK tertile was associated with a higher risk of death before and after adjustment for confounders (Crude model: hazard ratio (HR 1.77 (95% CI: 1.34-2.32 compared to the highest tertile; fully-adjusted model: HR 1.37 (95% CI: 1.02-1.86. Similar results were obtained with a time-dependent Cox model. The sCK level was not associated with the risk of ESRD.A low level of sCK is associated with an increased risk of death in a CKD population. sCK levels might reflect muscle mass and nutritional status.

  8. Whole-body vibration training elevates creatine kinase levels in sedentary subjects.

    Science.gov (United States)

    Gojanovic, Boris; Feihl, Francois; Liaudet, Lucas; Gremion, Gérald; Waeber, Bernard

    2011-07-07

    Whole body vibration (WBV) is an increasingly popular modality of muscle training, especially in sedentary subjects. We hypothesised that the vigorous muscle contractions elicited by WBV can cause muscle damage expressed as an elevation in muscle enzymes. Twenty inactive subjects, ten male and ten female, aged 22.7 ± 2.6, BMI 22.4 ± 2.1 were included based on the absence of regular physical activity as defined by international guidelines, and no history of recent trauma, musculoskeletal pathology, implanted prosthetics, cardiovascular disease or drug intake. The intervention consisted of one bout of high intensity WBV corresponding to a typical training session, involving all the major muscle groups. Plasma levels of muscle enzymes prior to and at 24, 48 and 96 hours post exercise (creatine kinase - CK, MB fraction, troponin I, aminotransferases and lactate dehydrogenase) were measured. In addition, blood lactate was assayed immediately after exercise. Delayed onset muscle soreness (DOMS) was evaluated using a visual analogical scale. Five participants (25%) showed a significant increase in post exercise CK levels (> double of baseline). Maximal value was 3520 U/l. No change was observed in CK-MB or troponin I. Lactate increased to 10.0 ± 2.4 in men and 6.9 ± 2.4 in women. All participants had some degrees of DOMS, without correlation to enzymatic changes. WBV can provoke high CK elevation in healthy, medication-free inactive subjects. Such an elevation is transient and harmless, but could be wrongly attributed to drug induced myopathy, as in patients treated with statins. Practitioners should bear this in mind before discontinuing a potential life saving drug.

  9. Sex differences in creatine kinase after acute heavy resistance exercise on circulating granulocyte estradiol receptors.

    Science.gov (United States)

    Wolf, Megan R; Fragala, Maren S; Volek, Jeff S; Denegar, Craig R; Anderson, Jeffrey M; Comstock, Brett A; Dunn-Lewis, Courtenay; Hooper, David R; Szivak, Tunde K; Luk, Hui-Ying; Maresh, Carl M; Häkkinen, Keijo; Kraemer, William J

    2012-09-01

    Previous research has shown reduced tissue disruption and inflammatory responses in women as compared to men following acute strenuous exercise. While the mechanism of this action is not known, estrogen may reduce the inflammatory response through its interaction with granulocytes. The purpose of this study was to determine if estrogen receptor β expression on granulocytes is related to sex differences in tissue disruption in response to an acute heavy resistance exercise protocol. Seven healthy, resistance-trained, eumenorrheic women (23 ± 3 years, 169 ± 9.1 cm, 66.4 ± 10.5 kg) and 8 healthy, resistance-trained men (25 ± 5 years, 178 ± 6.7 cm, 82.3 ± 9.33 kg) volunteered to participate in the study. Subjects performed an acute resistance exercise test consisting of six sets of five squats at 90% of the subject's one repetition maximum. Blood samples were obtained pre-, mid-, post-, and 1-, 6-, and 24-h postexercise. Blood samples were analyzed for 17-β-estradiol by ELISA, creatine kinase by colorimetric enzyme immunoassay, and estradiol receptors on circulating granulocytes through flow cytometry. Men had higher CK concentrations than women at baseline/control. Men had significantly higher CK concentrations at 24-h postexercise than women. No significant changes in estradiol β receptors were expressed on granulocytes after exercise or between sexes. While sex differences occur in CK activity in response to strenuous eccentric exercise, they may not be related to estradiol receptor β expression on granulocytes. Thus, although there are sex differences in CK expression following acute resistance exercise, the differences may not be attributable to estrogen receptor β expression on granulocytes.

  10. Creatine kinase as a marker of obesity in a multi-ethnic population.

    Science.gov (United States)

    Haan, Yentl C; Oudman, Inge; Diemer, Frederieke S; Karamat, Fares A; van Valkengoed, Irene G; van Montfrans, Gert A; Brewster, Lizzy M

    2017-02-15

    Creatine kinase (CK), the central regulatory enzyme of energy metabolism, is particularly high in type II skeletal muscle fibers, which are associated with insulin resistance and obesity. As resting plasma CK is mainly derived from skeletal muscle, we assessed whether plasma CK is associated with markers of obesity. In this cross-sectional study, we analyzed a random sample of the multi-ethnic population of Amsterdam, the Netherlands, consisting of 1444 subjects aged 34-60 years. The primary outcome was the independent association between plasma CK after rest and waist circumference. Other outcomes included waist-to-hip ratio and body mass index. Mean waist circumference increased from the first through the third CK tertile, respectively 90.3 (SD 13.4), 93.2 (SD 14.3), and 94.4 (SD 13.3) cm (p < 0.001 for differences between tertiles). The increase in waist circumference was 8.91 (95% CI 5.35 to 12.47) cm per log CK increase after adjustment for age, sex, African ethnicity, educational level, physical activity and plasma creatinine. Similarly, CK was independently associated with waist-to-hip ratio and body mass index, with an increase of respectively 0.05 (95% CI 0.03 to 0.07) and 3.6 (95% CI 2.3 to 5.0) kg/m(2) per log CK increase. Plasma CK is independently associated with measures of obesity in a multi-ethnic population. This is in line with the central role of type II skeletal muscle fibers in energy metabolism and obesity. Prospective studies should assess whether resting plasma CK could be an easy accessible marker of CK rich type II fiber predominance that helps identify individuals at risk for obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Creatine Kinase and Lactate Dehydrogenase Responses after Different Resistance and Aerobic Exercise Protocols.

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    Callegari, Gustavo A; Novaes, Jefferson S; Neto, Gabriel R; Dias, Ingrid; Garrido, Nuno D; Dani, Caroline

    2017-09-01

    The aim of this study was to investigate the responses of creatine kinase (CK) and lactate dehydrogenase (LDH) after performing different resistance and aerobic exercise protocols. Twelve recreationally trained men (age, 23.2 ± 5.6 years; body mass, 84.3 ± 9.3 kg; body height, 178.9 ± 4.5 cm; and BMI, 26.3 ± 2.3 kg·m2) volunteered to participate in this study. All subjects were randomly assigned to four experimental protocols (crossover): (a) aerobic training at 60% of VO2max, (b) aerobic training at 80% of VO2max, (c) a resistance exercise (RE) session with a bi-set protocol, and (d) an RE session with a multiple sets protocol. Blood samples were collected before, immediately after and 24 hours following the experimental protocols. After 24 hours, there was a significant increase in CK for the 80% of VO2max protocol vs. the bi-set RE session (p = 0.016). Immediately after the protocols, we observed a significant increase in LDH among certain groups compared to others, as follows: multiple sets RE session vs. 60% of VO2max, bi-set RE session vs. 60% of VO2max, multiple sets RE session vs. 80% of VO2max, and bi-set RE session vs. 80% of VO2max (p = 0.008, p = 0.013; p = 0.002, p = 0.004, respectively). In conclusion, aerobic exercise performed at 80% of VO2max appears to elevate plasma CK levels more than bi-set RE sessions. However, the bi-set and multiple sets RE sessions appeared to trigger greater levels of blood LDH compared to aerobic protocols performed at 60% and 80% of VO2max.

  12. Low-level laser therapy attenuates creatine kinase levels and apoptosis during forced swimming in rats.

    Science.gov (United States)

    Sussai, Daniela Aparecida; Carvalho, Paulo de Tarso Camillo de; Dourado, Doroty Mesquita; Belchior, Ana Carulina Guimarães; dos Reis, Filipe Abdalla; Pereira, Daniel Martins

    2010-01-01

    Studies suggest that high-intensity physical exercise can cause damage to skeletal muscles, resulting in muscle soreness, fatigue, inflammatory processes and cell apoptosis. The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on a decrease in creatine kinase (CK) levels and cell apoptosis. Twenty male Wistar rats were randomly divided into two equal groups: group 1 (control), resistance swimming; group 2 (LLLT), resistance swimming with LLLT. They were subjected to a single application of indium gallium aluminum phosphide (InGaAlP) laser immediately following the exercise for 40 s at an output power of 100 mW, wavelength 660 nm and 133.3 J/cm(2). The groups were subdivided according to sample collection time: 24 h and 48 h. CK was measured before and both 24 h and 48 h after the test. Samples of the gastrocnemius muscle were processed to determine the presence of apoptosis using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling. (There was a significant difference in CK levels between groups (P < 0.0001) as well as between the 24 h and 48 h levels in the control group, whereas there was no significant intra-group difference in the LLLT group at the same evaluation times. In the LLLT group there were 66.3 +/- 13.2 apoptotic cells after 24 h and 39.0 +/- 6.8 apoptotic cells after 48 h. The results suggest that LLLT influences the metabolic profile of animals subjected to fatigue by lowering serum levels of CK. This demonstrates that LLLT can act as a preventive tool against cell apoptosis experienced during high-intensity physical exercise.

  13. Cardiac troponin I and creatine kinase-MB release after different cardiac surgeries.

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    Mastro, Florinda; Guida, Pietro; Scrascia, Giuseppe; Rotunno, Crescenzia; Amorese, Lillà; Carrozzo, Alessandro; Capone, Giuseppe; Paparella, Domenico

    2015-06-01

    To conduct a comparative study of cardiac troponin I (cTnI) and MB isoenzyme of serum creatine kinase (CK-MB) after different cardiac surgeries. Consecutive cardiac operations under cardiopulmonary bypass (200 adults, 144 men, 68 ± 11 years): 67 coronary artery bypass graft (CABG), 27 aortic valve surgery, 21 mitral valve surgery, 11 thoracic aorta surgery, and 74 combined surgery. Postoperative cTnI and CK-MB were measured on admission to the ICU and at fixed time until the fifth postoperative day. Peak values of cTnI (median 5.8 ng/ml; interquartile range 3.6-11.9) and CK-MB (29.0 ng/ml; 15.6-60.4) were reached mainly within 18 h after the end of surgery (85% of cTnI and 95% of CK-MB highest determinations) without differences among groups. Cardiopulmonary bypass and cross-clamp time significantly correlated with markers' peak values. At multivariate analysis, mitral valve surgery showed greater cTnI, CK-MB, and their cumulative area under the curve than other isolated procedures. Thoracic aorta surgery showed lower cumulative area under the curve for both markers than CABG and combined surgery. Mitral valve surgery had significant later reduction of both markers in comparison with other procedures. No patient in mitral valve surgery group reached cTnI values in the normal laboratory range within 5 postoperative days. Release pattern of cTnI and CK-MB after heart surgery depends on the type of procedure. Mitral valve surgery was characterized by highest and longest elevation of postoperative markers' concentration. Determinants of differences in myocardial injury biomarkers and their prognostic value after valve surgery should be accurately assessed.

  14. Creatine Kinase and Lactate Dehydrogenase Responses After Different Resistance and Aerobic Exercise Protocols

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    Callegari Gustavo A.

    2017-08-01

    Full Text Available The aim of this study was to investigate the responses of creatine kinase (CK and lactate dehydrogenase (LDH after performing different resistance and aerobic exercise protocols. Twelve recreationally trained men (age, 23.2 ± 5.6 years; body mass, 84.3 ± 9.3 kg; body height, 178.9 ± 4.5 cm; and BMI, 26.3 ± 2.3 kg·m2 volunteered to participate in this study. All subjects were randomly assigned to four experimental protocols (crossover: (a aerobic training at 60% of VO2max, (b aerobic training at 80% of VO2max, (c a resistance exercise (RE session with a bi-set protocol, and (d an RE session with a multiple sets protocol. Blood samples were collected before, immediately after and 24 hours following the experimental protocols. After 24 hours, there was a significant increase in CK for the 80% of VO2max protocol vs. the bi-set RE session (p = 0.016. Immediately after the protocols, we observed a significant increase in LDH among certain groups compared to others, as follows: multiple sets RE session vs. 60% of VO2max, bi-set RE session vs. 60% of VO2max, multiple sets RE session vs. 80% of VO2max, and bi-set RE session vs. 80% of VO2max (p = 0.008, p = 0.013; p = 0.002, p = 0.004, respectively. In conclusion, aerobic exercise performed at 80% of VO2max appears to elevate plasma CK levels more than bi-set RE sessions. However, the bi-set and multiple sets RE sessions appeared to trigger greater levels of blood LDH compared to aerobic protocols performed at 60% and 80% of VO2max.

  15. C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension.

    Science.gov (United States)

    McQuary, Philip R; Liao, Chen-Yu; Chang, Jessica T; Kumsta, Caroline; She, Xingyu; Davis, Andrew; Chu, Chu-Chiao; Gelino, Sara; Gomez-Amaro, Rafael L; Petrascheck, Michael; Brill, Laurence M; Ladiges, Warren C; Kennedy, Brian K; Hansen, Malene

    2016-03-08

    Deficiency of S6 kinase (S6K) extends the lifespan of multiple species, but the underlying mechanisms are unclear. To discover potential effectors of S6K-mediated longevity, we performed a proteomics analysis of long-lived rsks-1/S6K C. elegans mutants compared to wild-type animals. We identified the arginine kinase ARGK-1 as the most significantly enriched protein in rsks-1/S6K mutants. ARGK-1 is an ortholog of mammalian creatine kinase, which maintains cellular ATP levels. We found that argk-1 is possibly a selective effector of rsks-1/S6K-mediated longevity and that overexpression of ARGK-1 extends C. elegans lifespan, in part by activating the energy sensor AAK-2/AMPK. argk-1 is also required for the reduced body size and increased stress resistance observed in rsks-1/S6K mutants. Finally, creatine kinase levels are increased in the brains of S6K1 knockout mice. Our study identifies ARGK-1 as a longevity effector in C. elegans with reduced RSKS-1/S6K levels. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension

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    Philip R. McQuary

    2016-03-01

    Full Text Available Deficiency of S6 kinase (S6K extends the lifespan of multiple species, but the underlying mechanisms are unclear. To discover potential effectors of S6K-mediated longevity, we performed a proteomics analysis of long-lived rsks-1/S6K C. elegans mutants compared to wild-type animals. We identified the arginine kinase ARGK-1 as the most significantly enriched protein in rsks-1/S6K mutants. ARGK-1 is an ortholog of mammalian creatine kinase, which maintains cellular ATP levels. We found that argk-1 is possibly a selective effector of rsks-1/S6K-mediated longevity and that overexpression of ARGK-1 extends C. elegans lifespan, in part by activating the energy sensor AAK-2/AMPK. argk-1 is also required for the reduced body size and increased stress resistance observed in rsks-1/S6K mutants. Finally, creatine kinase levels are increased in the brains of S6K1 knockout mice. Our study identifies ARGK-1 as a longevity effector in C. elegans with reduced RSKS-1/S6K levels.

  17. Clinical and Electron Microscopic Findings in Two Patients with Mitochondrial Myopathy Associated with Episodic Hyper-creatine Kinase-emia.

    Science.gov (United States)

    Nozuma, Satoshi; Okamoto, Yuji; Higuchi, Itsuro; Yuan, Junhui; Hashiguchi, Akihiro; Sakiyama, Yusuke; Yoshimura, Akiko; Higuchi, Yujiro; Takashima, Hiroshi

    2015-01-01

    Mitochondrial myopathy with episodic hyper-creatine kinase (CK)-emia (MIMECK) is a new disease entity characterized by episodic or persistent muscle weakness and elevated CK levels. We herein report two cases of MIMECK with the findings of histopathological studies. Histopathological examinations revealed strongly succinate dehydrogenase-reactive vessels. Electron microscopy showed abnormal mitochondria in the vessels and proliferating and vacuolated mitochondria under the sarcolemma. Both patients exhibited recurrent severe myalgia, weakness and increased CK levels. L-arginine treatment significantly ameliorated their muscle symptoms. These findings indicate that mitochondrial angiopathy plays an important role in the pathophysiology of MIMECK. L-arginine may be a potential therapeutic agent for this disorder.

  18. Reversible Amisulpride-induced Elevation of Creatine Kinase (CK): A Case Series from the German AMSP Pharmacovigilance Project.

    Science.gov (United States)

    Laoutidis, Z G; Konstantinidis, A; Grohmann, R; Luckhaus, C; Mobascher, J; Cordes, J

    2015-07-01

    The elevation of creatine kinase (CK) levels without neuroleptic malignant syndrome has been reported for several antipsychotics. We present here 4 cases with CK elevation induced by amisulpride, which have been registered for the German pharmacovigilance project, Arzneimittelsicherheit in der Psychiatrie (AMSP). The magnitude of the CK elevation ranged between 1, 498 IU/L and 21,018 IU/L. All 4 patients reported myalgia. In each case CK returned to normal after amisulpride discontinuation. In the fourth case, fluids were administered intravenously in order to prevent acute renal failure. None of the cases showed deterioration of renal function. Finally, we present recommendations for clinical practice.

  19. Role of creatine kinase isoenzymes on muscular and cardiorespiratory endurance: genetic and molecular evidence.

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    Echegaray, M; Rivera, M A

    2001-01-01

    The ability to perform well in activities that require muscular and cardiorespiratory endurance is a trait influenced, in a considerable part, by the genetic make-up of individuals. Early studies of performance and recent scans of the human genome have pointed at various candidate genes responsible for the heterogeneity of these phenotypes within the population. Among these are the genes for the various creatine kinase (CK) isoenzyme subunits. CK and phosphocreatine (PCr) form an important metabolic system for temporal and spatial energy buffering in cells with large variations in energy demand. The different CK isoenzyme subunits (CK-M and CK-B) are differentially expressed in the tissues of the body. Although CK-M is the predominant form in both skeletal and cardiac muscle, CK-B is expressed to a greater extent in heart than in skeletal muscle. Studies in humans and mice have shown that the expression of CK-B messenger RNA (mRNA) and the abundance and activity of the CK-MB dimer increase in response to cardiorespiratory endurance training. Increases in muscle tissue CK-B content can be energetically favourable because of its lower Michaelis constant (Km) for ADP. The activity of the mitochondrial isoform of CK (Scmit-CK) has also been significantly and positively correlated to oxidative capacity and to CK-MB activity in muscle. In mice where the CK-M gene has been knocked out, significant increases in fatigue resistance together with cellular adaptations increasing aerobic capacity have been observed. These observations have led to the notion that this enzyme may be responsible for fatigue under normal circumstances, most likely because of the local cell compartment increase in inorganic phosphate concentration. Studies where the Scmit-CK gene was knocked out have helped demonstrate that this isoenzyme is very important for the stimulation of aerobic respiration. Human studies of CK-M gene sequence variation have shown a significant association between a

  20. Correlation of Creatine Kinase Levels with Clinical Features and Survival in Amyotrophic Lateral Sclerosis

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    Hongfei Tai

    2017-07-01

    Full Text Available ObjectiveTo evaluate serum creatine kinase (CK levels of amyotrophic lateral sclerosis (ALS patients and to explore the relationship between CK levels and the clinical characteristics and survival prognosis of ALS patients.MethodsWe analyzed the CK levels of 185 ALS patients who underwent long-term follow-up. The relationship between CK levels and clinical features including sex, age, disease duration, site of onset, body mass index (BMI, serum creatinine (Cr, and spontaneous electromyographic activity was analyzed by univariate analysis and multiple linear regression. Kaplan–Meier and Cox proportional hazards models were used to explore whether CK levels were independently correlated with survival prognosis of ALS.ResultsBaseline serum CK was raised in 43% of participants. The median CK level was 160 U/L (range: 20–2,574 U/L, and 99% of patients had a baseline serum CK level less than 1,000 U/L. CK levels were significantly higher in male patients than in female patients [204 (169 versus 117 (111 U/L, p < 0.001] and in patients with limb onset ALS than with bulbar onset ALS (p < 0.001. CK levels were also correlated with serum Cr (p = 0.011 and the spontaneous potential score of electromyography (EMG (p = 0.037 but not correlated with age (p = 0.883, disease duration (p = 0.116, or BMI (p = 0.481. Log CK was independently correlated with survival of ALS patients (HR = 0.457, 95% confidence interval 0.221–0.947, p = 0.035 after adjusting for age, sex, site of onset, serum Cr, and BMI.ConclusionSerum CK levels of ALS patients were correlated with sex, site of onsite, serum Cr, and spontaneous activity in EMG. Serum CK could be an independent prognostic factor for survival of ALS patients.

  1. Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening.

    Science.gov (United States)

    Chang, Chih-Chun; Liou, Ching-Biau; Su, Ming-Jang; Lee, Yi-Chen; Liang, Chai-Ting; Ho, Jung-Li; Tsai, Huang-Wen; Yen, Tzung-Hai; Chu, Fang-Yeh

    2015-01-01

    For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy (1.35±0.28 vs 1.25±0.23, pMB-to-total-CK ratio more than 1.0 was colorectal cancer (1.42±0.28, 16.5%, n=56), followed by lung cancer (1.38±0.24, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies (1.44±0.41)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage (1.37±0.26 vs. 1.29±0.31, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis (1.48±0.30 vs. 1.30±0.21, pMB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

  2. Temporal changes in serum creatine kinase concentration and degree of muscle rigidity in 24 patients with neuroleptic malignant syndrome

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    Nisijima K

    2013-06-01

    Full Text Available Koichi Nisijima, Katutoshi ShiodaDepartment of Psychiatry, Jichi Medical University, Tochigi, JapanAbstract: Neuroleptic malignant syndrome (NMS is a dangerous adverse response to antipsychotic drugs. It is characterized by the four major clinical symptoms of hyperthermia, severe muscle rigidity, autonomic dysfunction, and altered mental state. Serum creatine kinase (CK elevation occurs in over 90% of NMS cases. In the present study, the detailed temporal changes in serum CK and degree of muscle rigidity, and the relationship between CK concentration and degree of muscle rigidity over the time course from fever onset, were evaluated in 24 affected patients. The results showed that serum CK peaked on day 2 after onset of fever and returned to within normal limits at day 12. Mild muscle rigidity was observed before the onset of fever in 17 of 24 cases (71%. Muscle rigidity was gradually exacerbated and worsened until day 4 after onset of fever. These findings confirm physicians' empirical understanding of serum CK concentrations and muscle rigidity in NMS based on data accumulated from numerous patients with the syndrome, and they indicate that serum CK may contribute to the early detection of NMS.Keywords: neuroleptic malignant syndrome, creatine kinase, muscle rigidity

  3. Aeromonas caviae alters the cytosolic and mitochondrial creatine kinase activities in experimentally infected silver catfish: Impairment on renal bioenergetics.

    Science.gov (United States)

    Baldissera, Matheus D; Souza, Carine F; Júnior, Guerino B; Verdi, Camila Marina; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Santos, Roberto C V; Vizzotto, Bruno S; Baldisserotto, Bernardo

    2017-09-01

    Cytosolic and mitochondrial creatine kinases (CK), through the creatine kinase-phosphocreatine (CK/PCr) system, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. However, the effects of bacterial infections on the kidney remain poorly understood and are limited only to histopathological analyses. Thus, the aim of this study was to investigate the involvement of cytosolic and mitochondrial CK activities in renal energetic homeostasis in silver catfish experimentally infected with Aeromonas caviae. Cytosolic CK activity decreased in infected animals, while mitochondrial CK activity increased compared to uninfected animals. Moreover, the activity of the sodium-potassium pump (Na(+), K(+)-ATPase) decreased in infected animals compared to uninfected animals. Based on this evidence, it can be concluded that the inhibition of cytosolic CK activity by A. caviae causes an impairment on renal energy homeostasis through the depletion of adenosine triphosphate (ATP) levels. This contributes to the inhibition of Na(+), K(+)-ATPase activity, although the mitochondrial CK activity acted in an attempt to restore the cytosolic ATP levels through a feedback mechanism. In summary, A. caviae infection causes a severe energetic imbalance in infected silver catfish, which may contribute to disease pathogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Coenzyme Q10 Effects on Creatine Kinase Activity and Mood in Geriatric Bipolar Depression

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    Forester, Brent P.; Zuo, Chun S.; Ravichandran, Caitlin; Harper, David G.; Du, Fei; Kim, Susan; Cohen, Bruce M.; Renshaw, Perry F.

    2015-01-01

    Introduction Despite the prevalence, associated comorbidities, and functional consequences of bipolar depression (BPD), underlying disease mechanisms remain unclear. Published studies of individuals with bipolar disorder implicate abnormalities in cellular energy metabolism. This study tests the hypotheses that the forward rate constant (kfor) of creatine kinase (CK) is altered in older adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that enhance mitochondrial function, increases kfor in elderly individuals with BPD treated with CoQ10 compared with untreated age- and sex-matched controls. Methods Ten older adults (ages 55 and above) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current episode depressed and 8 older controls underwent two 4 Tesla 31Phosphorus magnetic resonance spectroscopy (31PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate kfor. The BPD group was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2 weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale (MADRS) was used to measure depression symptom severity. Baseline kfor and changes in kfor were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with kfor changes using repeated measures linear regression. Results The kfor of CK was non-significantly lower for BPD than healthy controls at baseline (BPD mean (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02), Wilcoxon rank sum exact P = .40). The kfor for both CoQ10-treated BPD and controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon signed rank exact P = .01), with no significant difference in 8-week changes between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) = 0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory

  5. The Effect of Cigarette Smoking on Human Sperm Creatine Kinase Activity: As An ATP Buffering System in Sperm

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    Mohammad Ali Ghaffari

    2013-01-01

    Full Text Available Background: Spermatozoa are a group of cells that consume adenosine triphosphate (ATP rapidly.Creatine kinase (CK, produced by creatine phosphate, is an energy reservoir for the rapid bufferingand regeneration of ATP and can play an important role in sperm motility. Therefore, this studyinvestigates the effects of cigarette smoking on human sperm CK activity in males who smoke.Materials and Methods: In this case - control study, we obtained semen samples from male smokers(n=64 and nonsmokers (n=83. Smokers were categorized as light, moderate, or heavy smokersaccording to the daily number of cigarettes smoked and the number of years they have smoked. Datawere analyzed by the independent t test and Pearson’s analysis.Results: This investigation showed significantly lower sperm CK activity and movement in malesmokers compared to nonsmokers. In addition, it was demonstrated that cigarette smoking had adose-dependent effect on these parameters. There was a positive relation, although not significant,between sperm CK activity and its motility in male smokers.Conclusion: Smoking, by diminishing sperm CK activity, may potentially impair sperm energyhomeostasis and have an association with damage to sperm motility. This effect can be an importantmechanism that may cause infertility in male smokers. However, further research is necessary toelucidate the underlying mechanism of sperm motility damage caused by cigarette smoking.

  6. In Vitro Inhibition of Human Sperm Creatine Kinase by Nicotine,Cotinine and Cadmium, as a Mechanism in Smoker Men Infertility

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    Mohammad Ali Ghaffari

    2009-01-01

    Full Text Available Background: Nicotine, cotinine and cadmium are harmful components of cigarettes that have aneffect on human reproductive function. Although the effects of cigarette smoke on male reproductivefunction is characterized in several articles its mechanism of action is still unknown.In the present study, we investigate the effect of nicotine, cotinine and cadmium on human spermcreatine kinase activity in vitro.Materials and Methods: Total creatine kinase activity is measured in sperm homogenates afterchromatography on a diethylaminoethyl cellulose (DEAE-32 column.Results: We show that creatine kinase activity is significantly inhibited by nicotine (44%, cotinine(39% and cadmium (65% at a concentration of 60 μg/ml. Kinetic studies reveal that the inhibitoryeffect of nicotine, cotinine and cadmium are competitive in relation to creatine phosphate.Conclusion: Considering the importance of creatine kinase activity for normal sperm energymetabolism, our results suggest that inhibition of this enzyme by nicotine, cotinine and cadmium maybe an important mechanism in infertility amongst male smokers. However, further investigationsare needed to elucidate the exact mechanism of cigarette effect on male reproductive function atthe molecular level.

  7. Mitochondrial affinity for ADP is twofold lower in creatine kinase knock-out muscles - Possible role in rescuing cellular energy homeostasis

    NARCIS (Netherlands)

    ter Veld, F; Jeneson, JAL; Nicolay, K

    2005-01-01

    Adaptations of the kinetic properties of mitochondria in striated muscle lacking cytosolic (M) and/or mitochondrial (Mi) creatine kinase (CK) isoforms in comparison to wild-type (WT) were investigated in vitro. Intact mitochondria were isolated from heart and gastrocnemius muscle of WT and single- a

  8. Mitochondrial affinity for ADP is twofold lower in creatine kinase knock-out muscles - Possible role in rescuing cellular energy homeostasis

    NARCIS (Netherlands)

    ter Veld, F; Jeneson, JAL; Nicolay, K

    Adaptations of the kinetic properties of mitochondria in striated muscle lacking cytosolic (M) and/or mitochondrial (Mi) creatine kinase (CK) isoforms in comparison to wild-type (WT) were investigated in vitro. Intact mitochondria were isolated from heart and gastrocnemius muscle of WT and single-

  9. Dexamethasone effects on creatine kinase activity and insulin-like growth factor receptors in cultured muscle cells

    Science.gov (United States)

    Whitson, Peggy A.; Stuart, Charles A.; Huls, M. H.; Sams, Clarence F.; Cintron, Nitza M.

    1989-01-01

    The effect of dexamethasone on the activity of creatine kinase (CK) and the insulin-like growth factor I (IGF-I) binding were investigated using skeletal- and cardiac-muscle-derived cultured cell lines (mouse, C2C12; rat, L6 and H9c2). It was found that, in skeletal muscle cells, dexamethasone treatment during differentiation of skeletal-muscle cells caused dose-dependent increases in CK activity and increases in the degree of myotube formation, whereas cardiac cells (H9c2) exhibited very low CK activity during culture or dexamethasone treatment. Results for IGF-I binding were similar in all three cell lines. The IGF-I binding to dexamethasone-treated cells (50 nM for 24 hr on the day prior to confluence) resulted in an increased number of available binding sites, with no effect on the binding affinities.

  10. Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain

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    Samira S. Valvassori

    2013-12-01

    Full Text Available Objective: To investigate the effects of cannabidiol (CBD on mitochondrial complex and creatine kinase (CK activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg in an acute (single dose or chronic (once daily for 14 consecutive days regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex. Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV and CK in the rat brain. Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity by CBD could be an important mechanism implicated in the action of CBD.

  11. [Emoxipin in reperfusion of ischemic myocardium in dogs: effects on infarct size and plasma creatine kinase activity].

    Science.gov (United States)

    Konorev, E A; Polumiskov, V Iu; Avilova, O A; Golikova, A P

    1990-09-01

    The effects of synthetic antioxidant emoxypine on infarct size and plasma creatine kinase (CK) activity was studied on open-chest anesthetized dogs with 180-min myocardial ischemia followed by reperfusion. Emoxypine (10 and 40 mg/kg) was injected intravenously, beginning since 120th min of coronary artery occlusion. Emoxypine (10 mg/kg) resulted in infarct size limitation and reduction in plasma CK activity. An increase in dose of emoxypine to 40 mg/kg largely attenuated its protective effect on infarct size. CK activity during post-ischemic reperfusion was even higher in emoxypine (40 mg/kg) group compared with control. Augmented CK leakage from irreversibly injured myocardium to plasma under these experimental conditions may be owing to preservation of microvascular integrity and improving of drainage of infarcted tissue exerted by emoxypine.

  12. Dexamethasone effects on creatine kinase activity and insulin-like growth factor receptors in cultured muscle cells

    Science.gov (United States)

    Whitson, Peggy A.; Stuart, Charles A.; Huls, M. H.; Sams, Clarence F.; Cintron, Nitza M.

    1989-01-01

    The effect of dexamethasone on the activity of creatine kinase (CK) and the insulin-like growth factor I (IGF-I) binding were investigated using skeletal- and cardiac-muscle-derived cultured cell lines (mouse, C2C12; rat, L6 and H9c2). It was found that, in skeletal muscle cells, dexamethasone treatment during differentiation of skeletal-muscle cells caused dose-dependent increases in CK activity and increases in the degree of myotube formation, whereas cardiac cells (H9c2) exhibited very low CK activity during culture or dexamethasone treatment. Results for IGF-I binding were similar in all three cell lines. The IGF-I binding to dexamethasone-treated cells (50 nM for 24 hr on the day prior to confluence) resulted in an increased number of available binding sites, with no effect on the binding affinities.

  13. Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo.

    Science.gov (United States)

    Sömjen, D; Waisman, A; Kaye, A M

    1996-12-01

    We have compared the cell and tissue selective estrogenic and antiestrogenic activities of tamoxifen, raloxifene, ICI 164,384 and a permanently ionized derivative of tamoxifen--tamoxifen methiodide (TMI). This non-steroidal antiestrogen has limited ability to cross the blood brain barrier and is therefore less likely to cause the central nervous system disturbances caused by tamoxifen. We have used the stimulation of the specific activity of the "estrogen induced protein", creatine kinase BB, as a response marker in bone, cartilage, uterine and adipose cells and in rat skeletal tissues, uterus and mesometrial adipose tissue. In vitro, TMI, tamoxifen and raloxifene mimicked the agonistic action of 17beta-estradiol in ROS 17/2.8 rat osteogenic osteosarcoma, female calvaria, and SaOS2 human osteoblast cells. In Ishikawa endometrial cancer cells, tamoxifen showed reduced agonistic effects and raloxifene showed no stimulation. However, as antagonists, tamoxifen and raloxifene were equally effective in Ishikawa or SaOS2 cells. In immature rats, all four of the antiestrogens inhibited estrogen action in diaphysis, epiphysis, uterus and mesometrial adipose tissue; when administered alone, tamoxifen stimulated creatine kinase (CK) specific activity in all these tissues. Raloxifene and TMI, however, stimulated only the skeletal tissues and had no stimulatory effect in the uterus or mesometrial fat, and the pure antiestrogen ICI 164,384 showed no stimulatory effect in any of the tissues. The simultaneous injection of estrogen, plus an antiestrogen which acted as an agonist, resulted in lower CK activity than after injection of either agent alone. These differential effects, in vivo and in vitro, may point the way to a wider therapeutic choice of an appropriate antiestrogen which, although antagonizing E2 action in mammary cancer, can still protect against osteoporosis and cardiovascular disease and not stimulate the uterus with its attendant undesirable changes, or interfere

  14. Surface Electromyography Assessments of the Vastus medialis and Rectus femoris Muscles and Creatine Kinase after Eccentric Contraction Following Glutamine Supplementation.

    Science.gov (United States)

    Rahmani-Nia, Farhad; Farzaneh, Esmail; Damirchi, Arsalan; Majlan, Ali Shamsi; Tadibi, Vahid

    2014-03-01

    L-glutamine is the most abundant amino acid found in human muscle and plays an important role in protein synthesis and can reduce the levels of inflammation biomarkers and creatine kinase (CK) after training sessions. Delayed onset muscle soreness (DOMS) develops after intense exercise and is associated with an inflammatory response. The purpose of this study was to investigate the effect of glutamine supplementation on surface electromyography activity of the vastus medialis muscle (VMM) and rectus femoris muscle (RFM) and levels of creatine kinase after an eccentric contraction. SEVENTEEN HEALTHY MEN (AGE: 22.35±2.27yr; body mass: 69.91± 9.78kg; height: 177.08±4.32cm) were randomly assigned to experimental (n=9) and control groups (n=8) in a double-blind manner. In both groups, subjects were given L-glutamine supplementation (0.1g.kg(-1)) or placebo three times a week for 4 weeks. Median frequency (MDF) and mean power frequency (MPF) for VMM and RFM muscles and also CK measurements were performed before, 24h and 48 h after a resistance training session. The resistance training included 6 sets of eccentric leg extensions to exhaustion with 75% of 1RM. There was no significant difference between groups for MDF or MPF in VMM and RFM. The difference of CK level between the groups was also not significant. The results of this study indicate that glutamine supplementation has no positive effect on muscle injury markers after a resistance training session.

  15. Characterization of a functional recombinant human creatine kinase-MB isoenzyme prepared by tandem affinity purification from Escherichia coli.

    Science.gov (United States)

    Zou, Lihui; Su, Wen; Wang, Meng; Huang, Wei; Zhao, Haijian; Zhang, Enyi; Jin, Junhua; Xu, Hongtao; Xiao, Fei

    2017-07-01

    Creatine kinase isoform CK-MB has been widely applied as a biomarker of myocardial injury. While a variety of methods have been used to measure CK-MB activity or mass in clinical laboratories, a CK-MB standard is needed to eliminate between-method bias. Because the in vitro expression of human creatine kinase generates three isoenzymes, CK-MM, CK-MB, and CK-BB, it is important to establish an effective method to purify the isoform CK-MB from the mixture. In this study, we aimed at using tandem affinity purification (TAP) to purify recombinant CK-MB protein and evaluate its value in clinical laboratories. After the optimized sequence coding CK-M and CK-B were synthesized, they were combined with TAP tags (6His and SBP) and inserted into a pRSFDuet vector; then, the constructed 6His-CK-M-SBP-CK-B-pRSF plasmid was transformed into Escherichia coli BL21 (DE3) for expression. After TAP, we obtained purified CK-MB protein. We also did recovery testing using the engineered CK-MB and standard CK-MB (Randox) at different concentrations, and the results suggested that the engineered CK-MB could be used as the reference material. Moreover, the stability study of recombinant CK-MB showed high stability during long-term storage at -80 °C. In conclusion, the TAP-purified recombinant CK-MB protein may be a much better and cheaper standard or reference material for clinical laboratories.

  16. Physiological Function of Creatine Kinase and Sport%肌酸激酶的生理功能与运动

    Institute of Scientific and Technical Information of China (English)

    周多奇; 龚莉; 钱振宇

    2016-01-01

    肌酸激酶( creatine kinase,CK)是催化磷酸肌酸和ATP间高能磷酸基团转移的关键酶,它保持 ATP/ADP比例平衡和ATP的供给。肌酸激酶家族共有5种同工酶,分布于全身各种组织的需能部位。研究发现,CK酶在能量代谢中有重要作用,与肌肉收缩、神经功能、细胞膜的稳定性、细胞的能量反馈调节、有氧耐力有关。一些研究认为,CKM(肌型肌酸激酶,creatine kinase,muscle)基因多态性影响个体有氧运动能力和个体对耐力训练的敏感性。本文对这些成果作一综述,并对未来研究进行展望,以期为进一步的研究提供参考。%The creatine kinase (CK) is a key enzyme which catalyzes the transfer of high-energy phosphates between PCr and ATP, thus keeping cellular ATP-to-ADP ratios balanced and the ATP pool highly charged.Five isoenzymes in CK family were ex-pressed in regions consuming energy all over different tissues .Many experimental studies have revealed that CK may play important role during energy metabolism, and they were associated with muscle contraction, neurological function, stability of membranal, feedback regulation of energy metabolism and aerobic endurance performance.Other studies found that CKMM gene polymorphisms may contribute to individual aerobic endurance and its’ sensibility to endurance training.The purpose of this work is to provide a new background for the people who are studying in this field by attempting to analyze these results , and inspire future researches.

  17. Kinase/phosphatase overexpression reveals pathways regulating hippocampal neuron morphology.

    Science.gov (United States)

    Buchser, William J; Slepak, Tatiana I; Gutierrez-Arenas, Omar; Bixby, John L; Lemmon, Vance P

    2010-07-01

    Development and regeneration of the nervous system requires the precise formation of axons and dendrites. Kinases and phosphatases are pervasive regulators of cellular function and have been implicated in controlling axodendritic development and regeneration. We undertook a gain-of-function analysis to determine the functions of kinases and phosphatases in the regulation of neuron morphology. Over 300 kinases and 124 esterases and phosphatases were studied by high-content analysis of rat hippocampal neurons. Proteins previously implicated in neurite growth, such as ERK1, GSK3, EphA8, FGFR, PI3K, PKC, p38, and PP1a, were confirmed to have effects in our functional assays. We also identified novel positive and negative neurite growth regulators. These include neuronal-developmentally regulated kinases such as the activin receptor, interferon regulatory factor 6 (IRF6) and neural leucine-rich repeat 1 (LRRN1). The protein kinase N2 (PKN2) and choline kinase alpha (CHKA) kinases, and the phosphatases PPEF2 and SMPD1, have little or no established functions in neuronal function, but were sufficient to promote neurite growth. In addition, pathway analysis revealed that members of signaling pathways involved in cancer progression and axis formation enhanced neurite outgrowth, whereas cytokine-related pathways significantly inhibited neurite formation.

  18. Changes in creatine kinase and cortisol in National Collegiate Athletic Association Division I American football players during a season.

    Science.gov (United States)

    Kraemer, William J; Looney, David P; Martin, Gerard J; Ratamess, Nicholas A; Vingren, Jakob L; French, Duncan N; Hatfield, Disa L; Fragala, Maren S; Spiering, Barry A; Howard, Robert L; Cortis, Cristina; Szivak, Tunde K; Comstock, Brett A; Dunn-Lewis, Courtenay; Hooper, David R; Flanagan, Shawn D; Volek, Jeff S; Anderson, Jeffrey M; Maresh, Carl M; Fleck, Steven J

    2013-02-01

    The purpose of this study was to track creatine kinase (CK) and serum cortisol over an American college football season starting with the preseason practice. A secondary purpose was to observe changes in basic clinical chemistries. Twenty-two National Collegiate Athletic Association Division I football players (age: 20.4 ± 1.1 years, height: 188.27 ± 8.3 cm, weight: 115.8 ± 29.7 kg) volunteered to participate in this study. Each of the players had participated in the summer strength and conditioning supervised program. Resting blood samples were obtained just before the start of preseason practice (T-1), 2 weeks later (T-2), and the day after game 2 (T-3), game 4 (T-4), game 6 (T-5), and game 9 (T-6) of a 12-game season. Creatine kinase, a panel of clinical chemistries, cortisol, and testosterone were assayed at each time point. No significant changes in CK concentrations were observed over the season with peak values of each range ≤1,070.0 IU·L(-1), but the largest range was observed at T-6 after game 9 (119-2,834 IU·L(-1). The analysis of covariance analysis demonstrated that the number of plays in the ninth game (T-6) explained the magnitude of the changes in CK. No changes in serum cortisol concentrations were observed yet, again large variations existed with peak values of each range ≤465.0 nmol·L(-1). Clinical chemistries showed various significant changes from T-1, but none were considered clinically relevant changes for any player over the time course of the study. In conclusion, the strength and conditioning program before preseason camp or the structure of summer camp practices and the in-season strength and conditioning appeared to mute muscle damage and the stress response of cortisol. Such data demonstrate that changes in muscle damage and adrenal cortical stress over the season are minimal, yet large individual variations can be observed. Management of these variables appears to be related to optimal strength and conditioning and sports

  19. Resistance imparted by traditional Chinese medicines to the acute change of glutamic pyruvic transaminase, alkaline phosphatase and creatine kinase activities in rat blood caused by noise.

    Science.gov (United States)

    Zhu, Bei-Wei; Sun, Yu-Mei; Yun, Xia; Han, Song; Piao, Mei-Lan; Murata, Yoshiyuki; Tada, Mikiro

    2004-05-01

    The activities of serum glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP) and creatine kinase (CK) in rats injected or not with the Chinese medicines, Astragali, Rhodiolae and Ligusticum, were determined after noise exposure. Noise at 95 and 105 dB significantly increased the activities of GPT, ALP and CK, and showed a dependence on the exposure time. The injection of each medicine significantly suppressed the increased enzyme activities by 95 and 105 dB noise.

  20. Changes of Serum Creatine Kinase in Recruits during Physical Training%新兵体能训练对血清肌酸激酶的影响

    Institute of Scientific and Technical Information of China (English)

    罗显荣; 罗春生; 蒋崇福; 杨俊; 徐越; 李莎恩; 成艳君

    2013-01-01

    Objective To investigate the changes of serum creatine kinase (CK) in the recruits during physical training and supply reference for reasonable physical training. Methods A total of 114 recruits were randomly selected, and the changes of serum CK and creatine kinase isoenzyme-MB (CK-MB) were determined 1, 4, 12 and 20 weeks after training. Results The average values of CK and CK-MB 4 and 12 weeks after training were significantly higher than those 1 week after training (P<0. 05). Twenty weeks after training, the average values of CK and CK-MB returned to the normal level. Conclusion The physical training can greatly affect the serum CK and CK-MB levels of the recruits.%目的 探讨新兵体能训练期间血清肌酸激酶(creatine kinase,CK)的变化,为科学实施体能训练提供依据.方法 随机选择114名新兵,于训练1、4、12和20周时检测空腹血清肌酸激酶和同功酶(creatine kinase isoenzyme-MB,CK-MB)水平.结果 训练4周和12周时血清CK及CK-MB均明显高于训练1周时(P<0.05),训练20周时血清CK及CK-MB恢复正常水平.结论 新兵体能训练可明显影响血清CK和CK-MB水平.

  1. LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy

    Directory of Open Access Journals (Sweden)

    I.A. Meijer

    2015-12-01

    Full Text Available Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from the age of 4 years. Analysis of the LPIN1 gene that encodes lipin-1 revealed a novel homozygous frameshift mutation in exon 9, c.1381delC (p.Leu461SerfsX47, and complete uniparental isodisomy of maternal chromosome 2. This mutation is predicted to cause complete lipin-1 deficiency. The patient had six rhabdomyolytic crises, with creatine kinase (CK levels up to 300,000 U/L (normal, 30 to 200. Plasma CK remained elevated between crises. A treatment protocol was instituted, with early aggressive monitoring, hydration, electrolyte replacement and high caloric, high carbohydrate intake. The patient received dexamethasone during two crises, which was well-tolerated and in these episodes, peak CK values were lower than in preceding episodes. Studies of anti-inflammatory therapy may be indicated in lipin-1 deficiency.

  2. Efflux of Creatine Kinase from Isolated Soleus Muscle Depends on Age, Sex and Type of Exercise in Mice

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    Juozas Baltusnikas, Tomas Venckunas, Audrius Kilikevicius, Andrej Fokin, Aivaras Ratkevicius

    2015-06-01

    Full Text Available Elevated plasma creatine kinase (CK activity is often used as an indicator of exercise-induced muscle damage. Our aim was to study effects of contraction type, sex and age on CK efflux from isolated skeletal muscles of mice. The soleus muscle (SOL of adult (7.5-month old female C57BL/6J mice was subjected to either 100 passive stretches, isometric contractions or eccentric contractions, and muscle CK efflux was assessed after two-hour incubation in vitro. SOL of young (3-month old male and female mice was studied after 100 eccentric contractions. For adult females, muscle CK efflux was larger (p < 0.05 after eccentric contractions than after incubation without exercise (698 ± 344 vs. 268 ± 184 mU·h−1, respectively, but smaller (p < 0.05 than for young females after the same type of exercise (1069 ± 341 mU·h−1. Eccentric exercise-induced CK efflux was larger in muscles of young males compared to young females (2046 ± 317 vs 1069 ± 341 mU · h−1, respectively, p < 0.001. Our results show that eccentric contractions induce a significant increase in muscle CK efflux immediately after exercise. Isolated muscle resistance to exercise-induced CK efflux depends on age and sex of mice.

  3. Kinesiology Tape does not Affect Serum Creatine Kinase Level and Quadriceps Activity during Recovery from Delayed-Onset Muscle Soreness

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    Naoko Aminaka

    2017-01-01

    Full Text Available Background: Delayed-onset muscle soreness (DOMS causes muscle damage and edema that can hinder performance and increase risks for secondary injuries. Kinesiology Tape (KT may be an effective modality for aiding in recovery, however, no study has investigated the effects of KT on the physiological biomarkers such as serum creatine kinase (CK level, concurrently with measures of performance and function, during recovery from DOMS. Objective: Investigate the effects of KT on serum CK level, electromyographic (EMG activity of the quadriceps muscles, and performances of countermovement jump (CMJ and triple single-leg hop for distance (HopD during recovery from DOMS. Method: Fifty-eight healthy college-age participants were randomly assigned to KT (n=15, placebo (n=19, and control (n=24 groups. Serum CK level and quadriceps EMG activity and performance during CMJ and HopD were collected at baseline, immediately after repetitive eccentric quadriceps exercise, 48 hours, and 72 hours post-exercise. The EMG recording of rectus femoris, vastus medialis, and vastus lateralis during the CMJ and HopD were normalized to the baseline maximum voluntary isometric contraction. Results: A significant main effect of time on the serum CK level, EMG activity, and performance (p0.05. Conclusion: Taping interventions did not improve the serum CK level or muscle activity and performance during recovery from DOMS. Kinesiology tape may not be the first choice of method for enhancing recovery from DOMS in otherwise healthy individuals.

  4. The Response of Creatine Kinase Specific Activity in Rat Pituitary to Estrogenic Compounds and Vitamin D Less-Calcemic Analogs

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    D. Somjen

    2009-01-01

    Full Text Available We examined the response of rat female pituitary at different metabolic stages to treatments with estrogenic compounds and vitamin D analogs. Immature or ovariectomized (Ovx female rats responded by increased creatine kinase specific activity (CK to estradiol-17β (E2, genistein (G, daidzein (D, biochainin A (BA, quecertin (Qu, carboxy- G (cG, carboxy- BA (cBA, and raloxifene (Ral. The response was inhibited when Ral was injected together with the estrogens. CK was increased when hormones were injected daily into Ovx rats for 4 different time periods. Pretreatment with the less-calcemic vitamin D analogs JK 1624 F2-2 (JKF or QW 1624 F2-2 (QW followed by estrogenic injection resulted in increased response and sensitivity to E2 and loss of inhibition of E2 by Ral. CK was also increased by feeding with E2 or licorice or its components dose- and time- dependent in immature or Ovxrats. Diabetic female rats did not respond to increased doses of E2. In conclusion, rat female pituitary is estrogens-responsive organ, suggesting to consider its response for HRT in postmenopausal women for both beneficial and hazardous aspects.

  5. Cardiovascular function is not associated with creatine kinase activity in a black African population: The SABPA study.

    Science.gov (United States)

    Mels, Catharina M C; van Zyl, Caitlynd; Huisman, Hugo W

    2016-06-10

    Higher creatine kinase (CK) activity is associated with the development of cardiovascular disease in black African populations. We compared CK activity and investigated associations of blood pressure with CK activity in black and white men as well as black and white women. Ambulatory blood pressure, total peripheral resistance and pulse wave velocity of 197 black and 208 white participants were determined and serum CK activity was measured. Blood pressure and pulse wave velocity were higher in black men and women (all p resistance with CK activity, in the black African population. In white men, total peripheral resistance was associated with CK activity (R (2) = 0.32; β = 0.25; p = 0.009), whereas systolic blood pressure (R (2) = 0.46; β = 0.17; p = 0.03) and pulse pressure (R (2) = 0.31; β = 0.21; p = 0.01) were associated with CK activity in white women. The lack of associations in the black African population suggests that the link between a worse cardiovascular profile and CK activity may be overshadowed by other contributing factors. Whereas, the established link between cardiovascular function and CK activity in the white groups may be the result of enhanced smooth muscle cell contractility and/or attenuated nitric oxide synthesis capacity.

  6. Effects of different resistance exercise protocols on nitric oxide, lipid peroxidation and creatine kinase activity in sedentary males.

    Science.gov (United States)

    Güzel, Nevin Atalay; Hazar, Serkan; Erbas, Deniz

    2007-01-01

    The purpose of this study was to determine the changes of oxidative response and exercise-induced muscle damage after two different resistance exercise protocols. Whether training with low or high intensity resistance programs cause alterations in the activities of lipid peroxidation, nitric oxide (NOx), and creatine kinase (CK) activity in human plasma was investigated. Twenty untrained males participated into this study. Ten of the subjects performed high intensity resistance (HR) exercise circuit and the rest of them performed low intensity resistance (LR) exercise circuit of 4 different exercises as a single bout. Venous blood samples were drawn pre-exercise, immediately after the exercise, and at the 6(th), 24(th), 48(th) and the72(nd) hours of post-exercise. Samples were analyzed for markers of muscle damage (CK), lipid peroxidation (MDA) and NOx. NOx production increased in HR group (p resistance exercise protocol in this study caused a significant increase between pre and post-exercise values in both groups (p resistance exercise induces free radical production more than low intensity resistance exercise program. Key pointsHigh intensity resistance exercise caused increases in NOx, MDA and CK levels.Light intensity resistance exercises increased MDA and CK levels but did not affect NOx levels.Damage arose during resistance exercises may be related to the level of resistance applied.

  7. Effect of varying rest intervals between sets of assistance exercises on creatine kinase and lactate dehydrogenase responses.

    Science.gov (United States)

    Machado, Marco; Koch, Alexander J; Willardson, Jeffrey M; Pereira, Luis S; Cardoso, M Isabel; Motta, Michela K S; Pereira, Rafael; Monteiro, André N

    2011-05-01

    To examine the effects of different rest intervals between sets on serum creatine kinase (CK) and lactate dehydrogenase (LDH) activity, 10 men (age = 25.6 ± 2.2 years, height = 173.1 ± 7.1 cm, and body mass = 75.9 ± 10.0 kg) participated in a randomized within-subject design that involved 4 resistance exercise sessions. Each session consisted of 4 sets of 10 repetitions with 10 repetition maximum loads for the chest press, pullover, biceps curl, triceps extension, leg extension, and prone leg curl. The sessions differed only in the length of the rest interval between sets and exercises, specifically: 60, 90, 120, 180 seconds. Serum CK and LDH were significantly (p resistance exercise sessions invoked similar damage to the muscle fibers independent of the rest interval between sets. These data indicate that the accumulated volume of work is the primary determinant of muscle damage in trained subjects who are accustomed to resistance exercise with short rest intervals.

  8. Efflux of creatine kinase from isolated soleus muscle depends on age, sex and type of exercise in mice.

    Science.gov (United States)

    Baltusnikas, Juozas; Venckunas, Tomas; Kilikevicius, Audrius; Fokin, Andrej; Ratkevicius, Aivaras

    2015-06-01

    Elevated plasma creatine kinase (CK) activity is often used as an indicator of exercise-induced muscle damage. Our aim was to study effects of contraction type, sex and age on CK efflux from isolated skeletal muscles of mice. The soleus muscle (SOL) of adult (7.5-month old) female C57BL/6J mice was subjected to either 100 passive stretches, isometric contractions or eccentric contractions, and muscle CK efflux was assessed after two-hour incubation in vitro. SOL of young (3-month old) male and female mice was studied after 100 eccentric contractions. For adult females, muscle CK efflux was larger (p resistance to exercise-induced CK efflux depends on age and sex of mice. Key pointsMuscle lengthening contractions induce the highest CK efflux in vitro compared with similar protocol of isometric contractions or passive stretches.Muscle CK efflux in vitro is applicable in studying changes of sarcolemma permeability/integrity, a proxy of muscle damage, in response to muscle contractile activity.Isolated muscle resistance to exercise-induced CK efflux is greater in female compared to male mice of young age and is further increased in adult female mice.

  9. Quantitative analysis for isoforms of creatine kinase MM in plasma by chromatofocusing, with on-line monitoring of enzyme activity.

    Science.gov (United States)

    Nohara, R; Sobel, B E; Jaffe, A S; Abendschein, D R

    1988-02-01

    Changes in the proportions of individual isoforms of the MM isoenzyme of creatine kinase (CK; EC 2.7.3.2) in plasma promptly reflect both myocardial infarction and coronary recanalization. However, quantitative methods developed thus far are too slow or cumbersome for routine use in making clinical decisions. We report a convenient, quantitative chromatofocusing assay with on-line fluorometric detection of isoform activity in the column eluent that provides results within 40 min from the time of sample application. Sample eluted from a microbore chromatofocusing column (1.8-mL bed volume) is split between a reaction stream, into which CK reagents are added, and a reference stream. After incubation at 37 degrees C, NADPH formed by reaction of isoforms with CK reagent is detected at 340 nm. The system can detect activity of individual isoforms in plasma samples having total CK activity greater than or equal to 21 U/L (30 degrees C). Results correlated closely with those obtained by previously validated, but slow, chromatofocusing (r = 0.98, n = 30) and protein immunoblotting (r = 0.90, n = 20) procedures.

  10. Bruising in Slaughter Cattle and Its Relationship with Creatine Kinase Levels and Beef Quality as Affected by Animal Related Factors

    Science.gov (United States)

    Mpakama, T.; Chulayo, A. Y.; Muchenje, V.

    2014-01-01

    The objective of the study was to determine the effects of animal related factors on bruising in slaughter cattle, creatine kinase (CK) and beef quality. Three hundred and twenty one cattle from three breeds (108 Bonsmara, 130 Beefmaster and 83 Brahman) were used in this study. The animals were grouped as follows: Group 1 (16 months old), Group 2 (18 months old) and Group 3 (24 months old). At exsanguinations, blood samples for CK determination were collected using disposable vacutainer tubes. Muscularis longissimus thoracis et lumborum (LTL) was collected 24 h after slaughter to determine the colour (L*, a*, and b*) and ultimate pH (pHu) of beef. Breed, sex and age had significant effects (pbeef quality. Bonsmara breed had the highest (80%) bruising score percentage, CK (705.3±80.57 U/L) and pHu (6.3±0.05) values while the Bonsmara had the highest L* (24.8±0.78) a* (17.5±0.53) and b* (12.8±0.53) values. Higher CK levels were also observed in winter compared to summer, spring and autumn respectively. Therefore, animal factors (sex, breed and animal age at slaughter) contribute to the development of bruises and have an effect on the levels of CK and meat quality. It was also concluded that there is no significant relationship between meat parameters (L,* a*, and b*) and CK levels. PMID:25050007

  11. Multisystem Disease, Including Eosinophilia and Progressive Hyper-Creatine-Kinase-emia over 10 Years, Suggests Mitochondrial Disorder

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    Josef Finsterer

    2017-04-01

    Full Text Available Background: Eosinophilia has not been reported as a manifestation of a mitochondrial disorder (MID. Here, we report a patient with clinical features suggesting a MID and permanent eosinophilia, multisystem disease, and progressive hyper-creatine-kinase (CK-emia for at least 10 years. Materials and Methods: Methods applied included a clinical exam, blood chemical investigations, electrophysiological investigations, imaging, and invasive cardiological investigations. The patient was repeatedly followed up over several years. He required replacement cardiac surgery. Results: In a 57-year-old male, eosinophilia was first detected at the age of 44 years and has remained almost constantly present until today. In addition to eosinophilia, he developed progressive hyper-CK-emia at the age of 47 years. His history was further positive for hepatopathy, hyperlipidemia, hypothyroidism, renal insufficiency, spontaneous Achilles tendon rupture, double vision, exercise intolerance, muscle aching, mild hypoacusis, sensory neuropathy, seizures, and mitral insufficiency/stenosis requiring valve replacement therapy, oral anticoagulation, and pacemaker implantation. Based on the multisystem nature of his abnormalities and permanent hyper-CK-emia, a MID was suspected. Conclusion: Eosinophilia can be associated with a MID with myopathy, possibly as a reaction to myofiber necrosis. If eosinophilia is associated with progressive hyper-CK-emia and multisystem disease, a MID should be suspected.

  12. Association of Plasma Heat Shock Protein 70, Interleukin 6, and Creatine Kinase Concentrations in a Healthy, Young Adult Population

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    Carmen Contreras-Sesvold

    2015-01-01

    Full Text Available Variations of baseline plasma concentrations of creatine kinase (CK, heat shock protein 70 (HSP70, and interleukin 6 (IL-6 have been reported. We report categorical associations which may influence these protein levels. Methods. Blood was harvested for DNA and plasma protein analysis from 567 adults. Mean protein levels of CK, HSP70, and IL-6 were compared by sex, ethnicity, genetic variants—CKMM Nco1 (rs1803285, HSPA1B +A1538G (rs1061581, and IL6 G-174C (rs1800795—self-reported history of exercise, oral contraceptive use, and dietary supplement use. Results. SNP major allele frequencies for CKMM, HSPA1B, and IL6 were 70% A, 57% A, and 60%. Mean CK statistically differed by sex, ethnicity, oral contraceptives, and caffeine. Plasma HSP70 differed by caffeine and protein. Mean IL-6 concentration differed by sex, ethnicity, and genotype. Plasma IL-6 was significantly lower (29% in males (1.92 ± 0.08 pg/mL and higher (29% among African Americans (2.85 ± 0.50 pg/mL relative to the others. IL6 G-174C GG genotype (2.23 ± 0.14 pg/mL was 19% greater than CG or CC genotypes. Conclusion. Differences in baseline CK and IL-6 plasma protein concentrations are associated with genetics, sex, ethnicity, and the use of oral contraceptives, caffeine, and protein supplements in this young and athletic population.

  13. Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

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    Penitente, Arlete Rita; Leite, Ana Luísa Junqueira; de Paula Costa, Guilherme; Shrestha, Deena; Horta, Aline Luciano; Natali, Antônio J.; Neves, Clóvis A.; Talvani, Andre

    2015-01-01

    The protozoan Trypanosoma cruzi triggers an inflammatory process in mammalian heart causing events such as fibrosis, changes in the architecture and functionality in this organ. Enalapril, an angiotensin II-converting enzyme inhibitor, is a drug prescribed to ameliorate this heart dysfunction, and appears to exert a potential role in immune system regulation. Our aim was to evaluate the chronic cardiac inflammatory parameters after therapeutic treatment with enalapril and benznidazole in C57BL/6 mice infected with the VL-10 strain of T. cruzi. After infection, animals were treated with oral doses of enalapril (25 mg/kg), benznidazole (100 mg/kg), or both during 30 days. Morphometric parameters and levels of chemokines (CCL2, CCL5), IL-10, creatine kinases (CKs), and C-reactive protein were evaluated in the heart and serum at the 120th day of infection. Enalapril alone or in combination with benznidazole did not change the number of circulating parasites, but reduced cardiac leukocyte recruitment and total collagen in the cardiac tissue. Interestingly, the combination therapy (enalapril/benznidazole) also reduced the levels of chemokines, CK and CK-MB, and C-reactive proteins in chronic phase. In conclusion, during the chronic experimental T. cruzi infection, the combination therapy using enalapril plus benznidazole potentiated their immunomodulatory effects, resulting in a low production of biomarkers of cardiac lesions. PMID:26350447

  14. Evaluation of total creatine kinase levels in a spectrum of neuro-psychiatric disorders in a tertiary neurosciences centre

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    Anshu Gupta

    2015-01-01

    Full Text Available Introduction: To study usefulness of total creatine kinase (CK as a screening tool in various neurological and psychiatric disorders in emergency setting of a tertiary care hospital. Materials and Methods: A 1-year retrospective study was conducted on 102 patients with complaints pertaining to neurological and psychiatric disorders in a tertiary neurosciences centre in a metropolitan city. Blood samples in plain vial were received in Emergency Laboratory and total CK levels were measured by automated analyzer and its correlation with various diseases was analyzed. Results: It was observed that CK activity was raised in various psychiatric conditions-acute transient psychotic disorder, alcohol dependence syndrome, delirium, psychosis, mental retardation, catatonia, bipolar affective disorder (BAD, depression and mania and also in neurological disorders-seizures, meningitis, myasthenia gravis (multiple sclerosis, Guillain-Barre syndrome, extra pyramidal syndrome, neuroleptic malignant syndrome and infarct. Conclusion: This study demonstrated that CK is a sensitive and an important screening parameter in diagnosis and monitoring of various neurological and psychiatric disorders in emergency setting. It is also helpful in identifying people at high risk for various neuro-psychiatric diseases.

  15. Sequential Events in the Irreversible Thermal Denaturation of Human Brain-Type Creatine Kinase by Spectroscopic Methods

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    Yan-Song Gao

    2010-06-01

    Full Text Available The non-cooperative or sequential events which occur during protein thermal denaturation are closely correlated with protein folding, stability, and physiological functions. In this research, the sequential events of human brain-type creatine kinase (hBBCK thermal denaturation were studied by differential scanning calorimetry (DSC, CD, and intrinsic fluorescence spectroscopy. DSC experiments revealed that the thermal denaturation of hBBCK was calorimetrically irreversible. The existence of several endothermic peaks suggested that the denaturation involved stepwise conformational changes, which were further verified by the discrepancy in the transition curves obtained from various spectroscopic probes. During heating, the disruption of the active site structure occurred prior to the secondary and tertiary structural changes. The thermal unfolding and aggregation of hBBCK was found to occur through sequential events. This is quite different from that of muscle-type CK (MMCK. The results herein suggest that BBCK and MMCK undergo quite dissimilar thermal unfolding pathways, although they are highly conserved in the primary and tertiary structures. A minor difference in structure might endow the isoenzymes dissimilar local stabilities in structure, which further contribute to isoenzyme-specific thermal stabilities.

  16. A Fluorescence Immunochromatographic Assay Using Europium (III) Chelate Microparticles for Rapid, Quantitative and Sensitive Detection of Creatine Kinase MB.

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    Lai, Xiao-Hong; Liang, Rong-Liang; Liu, Tian-Cai; Dong, Zhi-Ning; Wu, Ying-Song; Li, Lin-Hai

    2016-05-01

    The isoenzyme creatine kinase MB is very important for diagnosis of acute myocardial infarction (AMI). Some CK-MB immunoassays are sensitive, accurate and available for clinical application, but they are expensive and time-consuming procedures. Furthermore, conventional fluorescence immunochromatographic assays (FL-ICAs) have suffered from background fluorescence interference and low analytical sensitivity. A rapid and simple FL-ICA with Eu (III) chelate polystyrene microparticles was developed to determine CK-MB in 50uL serum samples using a portable test strip reader by measuring the fluorescence peak heights of the test line (HT) and the control line (HC) in 12 min. The assay was reliable with a good correlation coefficient between HT/HC ratio and CK-MB concentration in samples. A linear range was 0.85-100.29 ng/mL for CK-MB, and the LOD was 0.029 ng/mL. The intra- and inter-assay coefficients of variation (CV) were both MB. The system performed well in interference experiments. Furthermore, a highly significant correlation (r = 0.9794, P MB samples. These results indicated that the Eu (III) chelate microparticles-based FL-ICA is simple, fast, highly sensitive, reliable, and reproducible for point-of-care testing of CK-MB concentrations in serum. Graphical Abstract ᅟ.

  17. Cerebral hemorrhage increases plasma concentrations of noradrenalin and creatine kinase MB fraction with induction of cardiomyocyte damage in rats.

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    Liang, Xiao-Min; Chen, Jia; Zhang, Tao; Liu, Juan; Jiang, Xiao-Jiang; Xu, Zhi-Qiang

    2014-12-01

    The incidence of cardiac damage is high during acute cerebral hemorrhage. The animal data on the relationship between cerebral apoplexy and cardiac damage are lacking. Thus, the aim of the study was to evaluate the effects of cerebral hemorrhage on plasma concentrations of monoamine transmitter noradrenalin (NA), creatine kinase muscle and brain (CK-MB) isoenzyme fraction, and cardiomyocyte changes in the rat model. In this study, 140 Wistar rats were randomly and equally divided into experimental and control groups, and collagenase was injected into the right caudate nucleus to induce cerebral hemorrhage in the experimental group. Plasma NA was analyzed using high-performance liquid chromatography with electrochemical detection and serum CK-MB was measured by enzyme reaction rate method. We found that both NA and CK-MB were elevated (p MB concentrations reached peak levels at 24 h which were found to be 3.52 ± 0.06 μg/L and 5.47 ± 0.49 μkat/L, respectively. Thereafter, NA and CK-MB concentrations decreased gradually. Plasma NA declined to the preoperative level (1.66 ± 0.03 μg/L) at 72 h, while CK-MB level (2.71 ± 0.17 μkat/L) was found to be still higher than its preoperative level. It was, therefore, concluded that plasma NA might be involved in the induction and development of cardiomyocytes damage during cerebral hemorrhage.

  18. Contribution of various lipid profile parameters in determining creatine kinase-MB levels in unstable angina patients.

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    Bagale, Kiran R; Ingle, Avinash S; Choudhary, Rajeev

    2016-01-01

    In India, the correlation of severity of minor myocardial damage with dyslipidemia has rarely been studied in patients of unstable angina (UA). Dyslipidemia is proven to be a major risk factor for developing acute coronary syndrome (ACS) but still there is doubt about the type of lipoproteins involved in causing minor myocardial damage occurring in UA patients of ACS. The aim of our study was to find out the contribution of various types of lipoproteins to predict the severity of minor myocardial damage occurring in the patients of UA. Correlation design was used for the study. A single group of individuals was selected. Data were collected on dependent variable creatine kinase-MB (CK-MB) and independent variables (lipid profile parameters). The study comprised fifty patients admitted in cardiac care unit with typical history of UA with electrocardiogram showing no ST-segment elevation. The severity of myocardial damage was assessed from on admission CK-MB levels. The lipid profile was estimated from fasting blood samples of all the patients. For the purpose of the study, Pearson correlation and multiple linear regression analysis methods were applied. The triacylglycerol (TAG), very-low-density lipoprotein (VLDL), total cholesterol/high-density lipoprotein (TC/HDL) showed significant positive correlation whereas HDL was negatively correlating with CK-MB levels. The TAG, VLDL, and TC/HDL were found to be significantly affecting the severity of myocardial damage in the patients of UA.

  19. Chaperone-like effect of the linker on the isolated C-terminal domain of rabbit muscle creatine kinase.

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    Chen, Zhe; Chen, Xiang-Jun; Xia, Mengdie; He, Hua-Wei; Wang, Sha; Liu, Huihui; Gong, Haipeng; Yan, Yong-Bin

    2012-08-01

    Intramolecular chaperones (IMCs), which are specific domains/segments encoded in the primary structure of proteins, exhibit chaperone-like activity against the aggregation of the other domains in the same molecule. In this research, we found that the truncation of the linker greatly promoted the thermal aggregation of the isolated C-terminal domain (CTD) of rabbit muscle creatine kinase (RMCK). Either the existence of the linker covalently linked to CTD or the supply of the synthetic linker peptide additionally could successfully protect the CTD of RMCK against aggregation in a concentration-dependent manner. Truncated fragments of the linker also behaved as a chaperone-like effect with lower efficiency, revealing the importance of its C-terminal half in the IMC function of the linker. The aggregation sites in the CTD of RMCK were identified by molecular dynamics simulations. Mutational analysis of the three key hydrophobic residues resulted in opposing effects on the thermal aggregation between the CTD with intact or partial linker, confirming the role of linker as a lid to protect the hydrophobic residues against exposure to solvent. These observations suggested that the linkers in multidomain proteins could act as IMCs to facilitate the correct folding of the aggregation-prone domains. Furthermore, the intactness of the IMC linker after proteolysis modulates the production of off-pathway aggregates, which may be important to the onset of some diseases caused by the toxic effects of aggregated proteolytic fragments.

  20. Reproducibility of creatine kinase reaction kinetics in human heart: a (31) P time-dependent saturation transfer spectroscopy study.

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    Bashir, Adil; Gropler, Robert

    2014-06-01

    Creatine kinase (CK) is essential for the buffering and rapid regeneration of adenosine triphosphate (ATP) in heart tissue. Herein, we demonstrate a (31) P MRS protocol to quantify CK reaction kinetics in human myocardium at 3 T. Furthermore, we sought to quantify the test-retest reliability of the measured metabolic parameters. The method localizes the (31) P signal from the heart using modified one-dimensional image-selected in vivo spectroscopy (ISIS), and a time-dependent saturation transfer (TDST) approach was used to measure CK reaction parameters. Fifteen healthy volunteers (22 measurements in total) were tested. The CK reaction rate constant (kf ) was 0.32 ± 0.05 s(-1) and the coefficient of variation (CV) was 15.62%. The intrinsic T1 for phosphocreatine (PCr) was 7.36 ± 1.79 s with CV = 24.32%. These values are consistent with those reported previously. The PCr/ATP ratio was equal to 1.94 ± 0.15 with CV = 7.73%, which is within the range of healthy subjects. The reproducibility of the technique was tested in seven subjects and inferred parameters, such as kf and T1 , exhibited good reliability [intraclass correlation coefficient (ICC) of 0.90 and 0.79 for kf and T1 , respectively). The reproducibility data provided in this study will enable the calculation of the power and sample sizes required for clinical and research studies. The technique will allow for the examination of cardiac energy metabolism in clinical and research studies, providing insight into the relationship between energy deficit and functional deficiency in the heart.

  1. Metabolic rates of ATP transfer through creatine kinase (CK Flux) predict clinical heart failure events and death.

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    Bottomley, Paul A; Panjrath, Gurusher S; Lai, Shenghan; Hirsch, Glenn A; Wu, Katherine; Najjar, Samer S; Steinberg, Angela; Gerstenblith, Gary; Weiss, Robert G

    2013-12-11

    Morbidity and mortality from heart failure (HF) are high, and current risk stratification approaches for predicting HF progression are imperfect. Adenosine triphosphate (ATP) is required for normal cardiac contraction, and abnormalities in creatine kinase (CK) energy metabolism, the primary myocardial energy reserve reaction, have been observed in experimental and clinical HF. However, the prognostic value of abnormalities in ATP production rates through CK in human HF has not been investigated. Fifty-eight HF patients with nonischemic cardiomyopathy underwent ³¹P magnetic resonance spectroscopy (MRS) to quantify cardiac high-energy phosphates and the rate of ATP synthesis through CK (CK flux) and were prospectively followed for a median of 4.7 years. Multiple-event analysis (MEA) was performed for HF-related events including all-cause and cardiac death, HF hospitalization, cardiac transplantation, and ventricular-assist device placement. Among baseline demographic, clinical, and metabolic parameters, MEA identified four independent predictors of HF events: New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), African-American race, and CK flux. Reduced myocardial CK flux was a significant predictor of HF outcomes, even after correction for NYHA class, LVEF, and race. For each increase in CK flux of 1 μmol g⁻¹ s⁻¹, risk of HF-related composite outcomes decreased by 32 to 39%. These findings suggest that reduced CK flux may be a potential HF treatment target. Newer imaging strategies, including noninvasive ³¹P MRS that detect altered ATP kinetics, could thus complement risk stratification in HF and add value in conditions involving other tissues with high energy demands, including skeletal muscle and brain.

  2. EFFECTS OF DIFFERENT RESISTANCE EXERCISE PROTOCOLS ON NITRIC OXIDE, LIPID PEROXIDATION AND CREATINE KINASE ACTIVITY IN SEDENTARY MALES

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    Nevin Atalay Güzel

    2007-12-01

    Full Text Available The purpose of this study was to determine the changes of oxidative response and exercise-induced muscle damage after two different resistance exercise protocols. Whether training with low or high intensity resistance programs cause alterations in the activities of lipid peroxidation, nitric oxide (NOx, and creatine kinase (CK activity in human plasma was investigated. Twenty untrained males participated into this study. Ten of the subjects performed high intensity resistance (HR exercise circuit and the rest of them performed low intensity resistance (LR exercise circuit of 4 different exercises as a single bout. Venous blood samples were drawn pre-exercise, immediately after the exercise, and at the 6th, 24th, 48th and the72nd hours of post-exercise. Samples were analyzed for markers of muscle damage (CK, lipid peroxidation (MDA and NOx. NOx production increased in HR group (p < 0.05. The MDA response to the two different resistance exercise protocol in this study caused a significant increase between pre and post-exercise values in both groups (p < 0.05. Also, there was a significant difference in the MDA level between the two groups in post-exercise values (p < 0.05 and higher values were observed in HR group. CK activities showed a significant increase in all post exercise values (p < 0.05 of both groups but there were no difference between HR and LR groups. These findings support that high intensity resistance exercise induces free radical production more than low intensity resistance exercise program

  3. Serum creatine kinase response to exercise during dexamethasone-induced insulin resistance in Quarter Horses with polysaccharide storage myopathy.

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    Firshman, Anna M; Valberg, Stephanie J; Karges, Tami L; Benedict, Luke E; Annandale, Erin J; Seaquist, Elizabeth R

    2005-10-01

    To determine effects of dexamethasone on insulin sensitivity, serum creatine kinase (CK) activity 4 hours after exercise, and muscle glycogen concentration in Quarter Horses with polysaccharide storage myopathy (PSSM). 4 adult Quarter Horses with PSSM. A 2 x 2 crossover design was used with dexamethasone (0.08 mg/kg) or saline (0.9% NaCl) solution administered IV every 48 hours. Horses were exercised on a treadmill daily for 3 wk/treatment with a 2-week washout period between treatments. Serum CK activity was measured daily 4 hours after exercise. At the end of each treatment period, serum cortisol concentrations were measured, a hyperinsulinemic euglycemic clamp (HEC) technique was performed, and muscle glycogen content was determined. Mean +/- SEM serum cortisol concentration was significantly lower after 48 hours for the dexamethasone treatment (0.38 +/- 0.08 mg/dL), compared with the saline treatment (4.15 +/- 0.40 mg/dL). Dexamethasone significantly decreased the rate of glucose infusion necessary to maintain euglycemia during the HEC technique, compared with the saline treatment. Muscle glycogen concentrations and mean CK activity after exercise were not altered by dexamethasone treatment, compared with the saline treatment. Dexamethasone significantly reduced whole-body insulin-stimulated glucose uptake in Quarter Horses with PSSM after a 3-week period but did not diminish serum CK response to exercise or muscle glycogen concentrations in these 4 horses. Therefore, a decrease in glucose uptake for 3 weeks did not appear to alleviate exertional rhabdomyolysis in these horses. It is possible that long-term treatment may yield other results.

  4. Creatine kinase rate constant in the human heart measured with 3D‐localization at 7 tesla

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    Robson, Matthew D.; Neubauer, Stefan; Rodgers, Christopher T.

    2016-01-01

    Purpose We present a new Bloch‐Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first‐order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four‐angle saturation transfer (FAST) method using amplitude‐modulated radiofrequency pulses, phosphorus Bloch‐Siegert B1+‐mapping to determine the per‐voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Methods Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1H localization). Results BOAST kfCK values were 0.281 ± 0.002 s−1 in the calf and 0.35 ± 0.05 s−1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg−1 s−1. The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. Conclusion BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10‐cm loop coil. Magn Reson Med 78:20–32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27579566

  5. Relationship Between Serum Creatine Kinase Isoenzyme MM Subbands and the Gradation of Coronary Stenosis in Patients with Unstable Angina Pectoris

    Institute of Scientific and Technical Information of China (English)

    Wu Ziqiang; Zhu shanju; Meng Suron; Sun Yueh

    2000-01-01

    Objective To observe the relationship between serum creatine kinase isoenzyme MM sub-bands (CKMM3/MM1 ratio) and the gradation of coronary stenosis and provide a simple, reliable, and economical method for identifying high-risk unstable angina pectoris (UAP). Mehtods Blood samples were drawn at different time after onset of chest pain in 21 patients with UAP and only once in 20 each volunteers for control. CKMM3/MM1 ratio was detected by nonserial buffer agarose gel electrophoresis. CKMB and CK were observed by velocity method. An emergent coronary arteriography was performed as soon as patients were admitted into hospital. Results Patients with UAP were divided into two subgroups:patients with elevated serum enzyme [P( + )] and patients with normal serum enzyme [P( - ) ] according to CKMM3/MM1 ratio < 0.5. Patients with UAP(+)had higher serum CKMM3/MM1 ratios from 0.5 to 12hrs and serum CKMB from 2 to 12 hrs than those with UAP( - ) and control ( P < 0.05) . Serum enzyme concentrations of patients with UAP whose coronary lumen had 90% or more than 90% stenosis were significantly higher than those whose coronary lumen had less than 90% stenosis (P<0.01) . AnyCKMM3/MM1 ratio was less than 1.0 and CK within the normal range in patients with UAP( + ) group. Conclusions CKMM3/MM1 ratios in patients with UAP can reflect severity of myocardial ischemia. Serum CKMM3/MM1 ratio provides a simple, reliable, and economical method for identifying high-risk UAP.

  6. High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential.

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    Uranbileg, Baasanjav; Enooku, Kenichiro; Soroida, Yoko; Ohkawa, Ryunosuke; Kudo, Yotaro; Nakagawa, Hayato; Tateishi, Ryosuke; Yoshida, Haruhiko; Shinzawa, Seiko; Moriya, Kyoji; Ohtomo, Natsuko; Nishikawa, Takako; Inoue, Yukiko; Tomiya, Tomoaki; Kojima, Soichi; Matsuura, Tomokazu; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

    2014-05-01

    We previously reported the increased serum mitochondrial creatine kinase (MtCK) activity in patients with hepatocellular carcinoma (HCC), mostly due to the increase in ubiquitous MtCK (uMtCK), and high uMtCK mRNA expression in HCC cell lines. We explored the mechanism(s) and the relevance of high uMtCK expression in HCC. In hepatitis C virus core gene transgenic mice, known to lose mitochondrial integrity in liver and subsequently develop HCC, uMtCK mRNA and protein levels were increased in HCC tissues but not in non-tumorous liver tissues. Transient overexpression of ankyrin repeat and suppressor of cytokine signaling box protein 9 (ASB9) reduced uMtCK protein levels in HCC cells, suggesting that increased uMtCK levels in HCC cells may be caused by increased gene expression and decreased protein degradation due to reduced ASB9 expression. The reduction of uMtCK expression by siRNA led to increased cell death, and reduced proliferation, migration and invasion in HCC cell lines. Then, consecutive 105 HCC patients, who underwent radiofrequency ablation with curative intent, were enrolled to analyze their prognosis. The patients with serum MtCK activity >19.4 U/L prior to the treatment had significantly shorter survival time than those with serum MtCK activity ≤ 19.4 U/L, where higher serum MtCK activity was retained as an independent risk for HCC-related death on multivariate analysis. In conclusion, high uMtCK expression in HCC may be caused by hepatocarcinogenesis per se but not by loss of mitochondrial integrity, of which ASB9 could be a negative regulator, and associated with highly malignant potential to suggest a poor prognosis.

  7. Effects of downhill and uphill exercises of equivalent submaximal intensities on selected blood cytokine levels and blood creatine kinase activity.

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    Pokora, I; Kempa, K; Chrapusta, S J; Langfort, J

    2014-08-01

    The study was aimed at comparing the effects of concentric (CONC) and eccentric (ECC) exercises of equivalent (in terms of relative work load expressed as a percentage of VO2max) moderate intensity on selected blood cytokine levels and blood creatine kinase (CK) activity. Twenty recreationally active healthy young male volunteers were randomized between two groups that performed a single 1 h bout of CONC (uphill running) or ECC (downhill running) exercise at 60% of the respective individual VO2max. Venous blood taken 1 h before, at the end, and 24 h after the exercise was processed for plasma and analyzed for CK activity and IL-6, IL-1β and TNFα levels. There was no between-group difference in these cytokines prior to or just after the exercise, and in pre-exercise CK activity. The cytokines elevated significantly and similarly in both groups during the exercise, with no significant change in CK activity. Twenty-four hours later, CK activity and IL-6 were at pre-exercise levels in the CONC group, but showed further major increases in the ECC group, resulting in marked between-group differences in these indices. Changes in IL-1β and TNFα levels during the recovery period showed only minor differences between the study groups and produced no significant between-group difference in these cytokines. However, IL-1β level normalized in the ECC but not in the CONC group. The study suggests that moderate intensity ECC exercise compared to CONC exercise of equivalent relative work load results in considerably greater muscle damage and its related elevation in circulating IL-6, but it does not cause a major systemic inflammatory response.

  8. The Effect of Gender and Menstrual Phase on Serum Creatine Kinase Activity and Muscle Soreness Following Downhill Running.

    Science.gov (United States)

    Oosthuyse, Tanja; Bosch, Andrew N

    2017-02-23

    Serum creatine kinase (CK) activity reflects muscle membrane disruption. Oestrogen has antioxidant and membrane stabilising properties, yet no study has compared the CK and muscle soreness (DOMS) response to unaccustomed exercise between genders when all menstrual phases are represented in women. Fifteen eumenorrhoeic women (early follicular, EF (n = 5); late follicular, LF (n = 5); mid-luteal, ML (n = 5) phase) and six men performed 20 min of downhill running (-10% gradient) at 9 km/h. Serum CK activity and visual analogue scale rating of perceived muscle soreness were measured before, immediately, 24-h, 48-h and 72-h after exercise. The 24-h peak CK response (relative to pre-exercise) was similar between women and men (mean change (95% confidence interval): 58.5 (25.2 to 91.7) IU/L; 68.8 (31.3 to 106.3) IU/L, respectively). However, serum CK activity was restored to pre-exercise levels quicker in women (regardless of menstrual phase) than men; after 48-h post exercise in women (16.3 (-4.4 to 37.0) IU/L; 56.3 (37.0 to 75.6) IU/L, respectively) but only after 72-h in men (14.9 (-14.8 to 44.6) IU/L). Parallel to the CK response, muscle soreness recovered by 72-h in men. Conversely, the women still reported muscle soreness at 72-h despite CK levels being restored by 48-h; delayed recovery of muscle soreness appeared mainly in EF and LF. The CK and DOMS response to downhill running is gender-specific. The CK response recovers quicker in women than men. The CK and DOMS response occur in concert in men but not in women. The DOMS response in women is prolonged and may be influenced by menstrual phase.

  9. The Effect of Gender and Menstrual Phase on Serum Creatine Kinase Activity and Muscle Soreness Following Downhill Running

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    Tanja Oosthuyse

    2017-02-01

    Full Text Available Serum creatine kinase (CK activity reflects muscle membrane disruption. Oestrogen has antioxidant and membrane stabilising properties, yet no study has compared the CK and muscle soreness (DOMS response to unaccustomed exercise between genders when all menstrual phases are represented in women. Fifteen eumenorrhoeic women (early follicular, EF (n = 5; late follicular, LF (n = 5; mid-luteal, ML (n = 5 phase and six men performed 20 min of downhill running (−10% gradient at 9 km/h. Serum CK activity and visual analogue scale rating of perceived muscle soreness were measured before, immediately, 24-h, 48-h and 72-h after exercise. The 24-h peak CK response (relative to pre-exercise was similar between women and men (mean change (95% confidence interval: 58.5 (25.2 to 91.7 IU/L; 68.8 (31.3 to 106.3 IU/L, respectively. However, serum CK activity was restored to pre-exercise levels quicker in women (regardless of menstrual phase than men; after 48-h post exercise in women (16.3 (−4.4 to 37.0 IU/L; 56.3 (37.0 to 75.6 IU/L, respectively but only after 72-h in men (14.9 (−14.8 to 44.6 IU/L. Parallel to the CK response, muscle soreness recovered by 72-h in men. Conversely, the women still reported muscle soreness at 72-h despite CK levels being restored by 48-h; delayed recovery of muscle soreness appeared mainly in EF and LF. The CK and DOMS response to downhill running is gender-specific. The CK response recovers quicker in women than men. The CK and DOMS response occur in concert in men but not in women. The DOMS response in women is prolonged and may be influenced by menstrual phase.

  10. EFFECTS OF DOWNHILL AND UPHILL EXERCISES OF EQUIVALENT SUBMAXIMAL INTENSITIES ON SELECTED BLOOD CYTOKINE LEVELS AND BLOOD CREATINE KINASE ACTIVITY

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    I. Pokora

    2014-08-01

    Full Text Available The study was aimed at comparing the effects of concentric (CONC and eccentric (ECC exercises of equivalent (in terms of relative work load expressed as a percentage of VO2max moderate intensity on selected blood cytokine levels and blood creatine kinase (CK activity. Twenty recreationally active healthy young male volunteers were randomized between two groups that performed a single 1 h bout of CONC (uphill running or ECC (downhill running exercise at 60% of the respective individual VO2max. Venous blood taken 1 h before, at the end, and 24 h after the exercise was processed for plasma and analyzed for CK activity and IL-6, IL-1β and TNFα levels. There was no between-group difference in these cytokines prior to or just after the exercise, and in pre-exercise CK activity. The cytokines elevated significantly and similarly in both groups during the exercise, with no significant change in CK activity. Twenty-four hours later, CK activity and IL-6 were at pre-exercise levels in the CONC group, but showed further major increases in the ECC group, resulting in marked between-group differences in these indices. Changes in IL-1β and TNFα levels during the recovery period showed only minor differences between the study groups and produced no significant between-group difference in these cytokines. However, IL-1β level normalized in the ECC but not in the CONC group. The study suggests that moderate intensity ECC exercise compared to CONC exercise of equivalent relative work load results in considerably greater muscle damage and its related elevation in circulating IL-6, but it does not cause a major systemic inflammatory response.

  11. The impact of a repeated bout of eccentric exercise on muscular strength, muscle soreness and creatine kinase.

    Science.gov (United States)

    Smith, L L; Fulmer, M G; Holbert, D; McCammon, M R; Houmard, J A; Frazer, D D; Nsien, E; Israel, R G

    1994-01-01

    The purpose of this study was to determine if there were any beneficial or detrimental effects regarding delayed onset muscle soreness (DOMS), serum creatine kinase (CK), and maximum concentric strength at 80% of 1-RMconc, if a bout of eccentric exercise was repeated at 48 h after an initial bout. A secondary purpose was to determine whether unaccustomed eccentrics might affect plasma cholesterol (TC). Twenty-six men were randomly assigned to a control (Group 1) or experimental group (Group 2). Both groups performed three sets (12 repetitions per set) of the eccentric phase of a chest press, at 80% of one repetition maximum (1-RMconc); Group 2 repeated this exercise 48 h later. DOMS and CK were measured before, and every 24 h for 8 days after; TC was measured before, and every 24 h for 4 days. Maximum strength during the concentric phase of a chest press (1-RMconc) was measured before and at 48-h intervals after. A repeated measures analysis of variance revealed a significant time effect (P < 0.05) for DOMS, CK and strength, but no significant difference between groups (P < 0.05). An interesting finding was the significant (P < 0.05) reduction in TC at 24, 48 and 72 h, after exercise in both groups, which we hypothesized was associated with cellular repair. From these results we concluded that when a bout of eccentrics is repeated 48 h after an initial bout, there is no change in the characteristic time-course and/or intensity of DOMS, CK or 1-RMconc. PMID:7894959

  12. The Effect of One Session Continuous and Intermittent Aerobic Exercise on Blood Responses of HSP72 , Cortisol and Creatine Kinase

    Directory of Open Access Journals (Sweden)

    M. Amani

    2013-10-01

    Full Text Available Introduction & Objective: Heat shock proteins help the cells’ ability to keep their structures against different stresses. The purpose of this study was to investigate the effect of one ses-sion continuous and intermittent aerobic exercise on blood responses of HSP72, cortisol and creatine kinase (CK. Materials & Methods: This study is semi-experimental in which 21 male student athletes were divided in continuous group (n=7, intermittent group (n=7 and control group (n=7. Exer-cise protocol of continuous group included 1 hour running with 80% maximum heart rate in-tensity and that of intermittent group was 3 stages of 20 minute running with the same inten-sity as of continuous group . Blood sampling of basal, pre exercise, immediately after exer-cise and 90 minutes after exercise were gathered and the amounts of HSP72, cortisol and CK, were measured by ELISA, RIA and Enzymatic methods respectively. The data was analyzed with one way ANOVA and repeated measure analysis of variance at P?0.05 significance level. Results: HSP72 levels in the continuous group and intermittent group despite an increase in the average did not show a statistically significant difference. Changes between the groups were significant in immediately after exercise and 90 minutes after exercise (P.values respectively 0.017 and 0.002. CK changes in continuous group were significant but cortisol changes in different stages hadn’t significant difference Conclusion: Exercise with its role associated with cortisol and CK will stimulate HSP72 and continuous exercise will make further increase in HSP72 and CK increasing leads to a greater HSP72 response. (Sci J Hamadan Univ Med Sci 2013; 20 (3:223-231

  13. Methods of creatine kinase-MB analysis to predict mortality in patients with myocardial infarction treated with reperfusion therapy.

    Science.gov (United States)

    Lopes, Renato D; Lokhnygina, Yuliya; Hasselblad, Victor; Newby, Kristin L; Yow, Eric; Granger, Christopher B; Armstrong, Paul W; Hochman, Judith S; Mills, James S; Ruzyllo, Witold; Mahaffey, Kenneth W

    2013-05-02

    Larger infarct size measured by creatine kinase (CK)-MB release is associated with higher mortality and has been used as an important surrogate endpoint in the evaluation of new treatments for ST-segment elevation myocardial infarction (STEMI). Traditional approaches to quantify infarct size include the observed CK-MB peak and calculated CK-MB area under the curve (AUC). We evaluated alternative approaches to quantifying infarct size using CK-MB values, and the relationship between infarct size and clinical outcomes. Of 1,850 STEMI patients treated with reperfusion therapy in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (percutaneous coronary intervention (PCI)-treated) and the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) (fibrinolytic-treated) trials, 1,718 (92.9%) (COMMA, n = 868; COMPLY, n = 850) had at least five of nine protocol-required CK-MB measures. In addition to traditional methods, curve-fitting techniques were used to determine CK-MB AUC and estimated peak CK-MB. Cox proportional hazards modeling assessed the univariable associations between infarct size and mortality, and the composite of death, heart failure, shock and stroke at 90 days. In COMPLY, CK-MB measures by all methods were significantly associated with higher mortality (hazard ratio range per 1,000 units increase: 1.09 to 1.13; hazard ratio range per 1 standard deviation increase: 1.41 to 1.62; P MB measures were statistically significant in both the COMMA and COMPLY trials. Sophisticated curve modeling is an alternative to infarct-size quantification in STEMI patients, but it provides information similar to that of more traditional methods. Future studies will determine whether the same conclusion applies in circumstances other than STEMI, or to studies with different frequencies and patterns of CK-MB data collection.

  14. Significant Association of Serum Adiponectin and Creatine Kinase-MB Levels in ST-Segment Elevation Myocardial Infarction.

    Science.gov (United States)

    Natsukawa, Tomoaki; Maeda, Norikazu; Fukuda, Shiro; Yamaoka, Masaya; Fujishima, Yuya; Nagao, Hirofumi; Sato, Fumi; Nishizawa, Hitoshi; Sawano, Hirotaka; Hayashi, Yasuyuki; Funahashi, Tohru; Kai, Tatsuro; Shimomura, Iichiro

    2017-08-01

    Adiponectin, an adipocyte-specific secretory protein, abundantly exists in the blood stream while its concentration paradoxically decreases in obesity. Hypoadiponectinemia is one of risks of cardiovascular diseases. However, impact of serum adiponectin concentration on acute ischemic myocardial damages has not been fully clarified. The present study investigated the association of serum adiponectin and creatine kinase (CK)-MB levels in subjects with ST-segment elevation myocardial infarction (STEMI). This study is a physician-initiated observational study and is also registered with the University Hospital Medical Information Network (Number: UMIN 000014418). Patients were admitted to Senri Critical Care Medical Center, given a diagnosis of STEMI, and treated by primary percutaneous coronary intervention (PCI). Finally, 49 patients were enrolled and the association of serum adiponectin, CK-MB, and clinical features were mainly analyzed. Serum adiponectin levels decreased rapidly and reached the bottom at 24 hours after recanalization. Such reduction of serum adiponectin was inversely correlated with the area under the curve (AUC) of serum CK-MB (p=0.013). Serum adiponectin concentrations were inversely correlated with AUC of serum CK-MB. In multivariate analysis, serum adiponectin concentration on admission (p=0.002) and collateral (p=0.037) were significantly and independently correlated with serum AUC of CK-MB. Serum AUC of CK-MB in STEMI subjects was significantly associated with serum adiponectin concentration on admission and reduction of serum adiponectin levels from baseline to bottom. The present study may provide a possibility that serum adiponectin levels at acute phase are useful in the prediction for prognosis after PCI-treated STEMI subjects.

  15. Predictors of Left Ventricle Remodeling: Combined Plasma B-type Natriuretic Peptide Decreasing Ratio and Peak Creatine Kinase-MB.

    Science.gov (United States)

    Hsu, Jen-Te; Chung, Chang-Min; Chu, Chi-Ming; Lin, Yu-Shen; Pan, Kuo-Li; Chang, Jung-Jung; Wang, Po-Chang; Chang, Shih-Tai; Yang, Teng-Yao; Jang, Shih-Jung; Yang, Tsung-Han; Hsiao, Ju-Feng

    2017-01-01

    Background: Previous studies reported that patients who had an acute myocardial infarction (AMI) have found that measuring B-type natriuretic peptide (BNP) during the subacute phase of left ventricular (LV) remodeling can predict the possible course of LV remodeling. This study assessed the use of serial BNP serum levels combined with early creatine kinase-MB (CK-MB) to predict the development of significant LV remodeling in AMI patients. Methods: Nighty-seven patients with new onset AMI were assessed using serial echocardiographic studies and serial measurements of BNP levels, both performed on day-2 (BNP1), day-7 (BNP2), day-90 (BNP3), and day-180 (BNP4) after admission. LV remodeling was defined as >20% increase in biplane LV end-diastolic volume on day-180 compared to baseline (day-2). Results: Patients were divided into LV remodeling [LVR(+)] and non LV remodeling [LVR(-)] groups. No first-week BNP level was found to predict remodeling. However, the two groups had significantly different day-90 BNP level (208.1 ± 263.7 pg/ml vs. 82.4 ± 153.7 pg/ml, P = 0.039) and significantly different 3-month BNP decrease ratios ( R BNP13) (14.4 ± 92.2% vs. 69.4 ± 25.9%, P MB (cut-off 48.2 ng/ml; AUC = 0.672; P = 0.014) was another independent predictor of remodeling. Additionally, combining peak CK-MB and R BNP13 offered an excellent discrimination for half-year remodeling when assessed by ROC curve (AUC = 0.818, P MB additionally offered an incremental power to the predictions derived from serial BNP examinations.

  16. EFFECTS OF AMANTADINE ON BEHAVIOR, RESPIRATORY CHAIN ENZYMES AND CREATINE KINASE IN AN ANIMAL MODEL OF SCHIZOPHRENIA

    Directory of Open Access Journals (Sweden)

    David de Lucena

    2013-03-01

    Full Text Available Introduction: Glutamate dysregulation may be involved in the pathophysiology of schizophrenia, and NMDA antagonists seem to be effective in its treatment. We evaluated the efficacy of amantadine (AMA in preventing ketamine (KET-induced effects in an animal model of schizophrenia. Methods: Adult Wistar rats received 10 mg/kg AMA for 10 days, followed by 7 days of 25 mg/kg KET ip. Thirty minutes after the last injection, rats were placed in an open-field apparatus for 60 minutes and killed by decapitation afterwards. Amygdala, hippocampus, prefrontal cortex and striatum were isolated and analyzed for creatine kinase (CK and respiratory chain enzyme activities. Results: KET increased crossings and reduced grooming, which was not prevented by AMA. KET also increased stereotypic movements, which was partially prevented by AMA. As for CK activity, KET increased it in the prefrontal cortex, striatum and amygdala, and AMA prevented it only in prefrontal cortex and striatum. The activity of complex I was not altered by KET, however, AMA+KET increased it in the striatum and amygdala. KET increased the activity of complex II in the striatum as well, whereas AMA+KET increased it in hippocampus, prefrontal cortex, and striatum. KET did not alter complex I-III activity, whereas AMA+KET increased it in hippocampus and amygdala. AMA+KET also increased complex IV activity in hippocampus and striatum, whereas KET had no effect on this activity. Conclusion: AMA did not prevent most of KET-induced alterations. New animal models should be employed in the study of AMA as a potential novel drug for schizophrenia.

  17. 血清肌酸激酶在游泳运动中的应用%Application of Serum Creatine Kinase in Swimming Sports

    Institute of Scientific and Technical Information of China (English)

    刘海涛; 杨钦

    2012-01-01

    本文通过查阅相关文献,阐述了肌酸激酶,分析了血清肌酸激酶与运动训练的关系,如何利用血清肌酸激酶对游泳运动进行监控以及在利用血清肌酸激酶监控时需要考虑的影响因素。%Through using the method of literature review, this paper explains the serum ereafine kinase, analyzes the relationship between serum creatine kinase and sports training, howto use the serum ereatine kinase to monitor swimming training and factors need to be considered.

  18. Predictors of Left Ventricle Remodeling: Combined Plasma B-type Natriuretic Peptide Decreasing Ratio and Peak Creatine Kinase-MB

    Science.gov (United States)

    Hsu, Jen-Te; Chung, Chang-Min; Chu, Chi-Ming; Lin, Yu-Shen; Pan, Kuo-Li; Chang, Jung-Jung; Wang, Po-Chang; Chang, Shih-Tai; Yang, Teng-Yao; Jang, Shih-Jung; Yang, Tsung-Han; Hsiao, Ju-Feng

    2017-01-01

    Background: Previous studies reported that patients who had an acute myocardial infarction (AMI) have found that measuring B-type natriuretic peptide (BNP) during the subacute phase of left ventricular (LV) remodeling can predict the possible course of LV remodeling. This study assessed the use of serial BNP serum levels combined with early creatine kinase-MB (CK-MB) to predict the development of significant LV remodeling in AMI patients. Methods: Nighty-seven patients with new onset AMI were assessed using serial echocardiographic studies and serial measurements of BNP levels, both performed on day-2 (BNP1), day-7 (BNP2), day-90 (BNP3), and day-180 (BNP4) after admission. LV remodeling was defined as >20% increase in biplane LV end-diastolic volume on day-180 compared to baseline (day-2). Results: Patients were divided into LV remodeling [LVR(+)] and non LV remodeling [LVR(-)] groups. No first-week BNP level was found to predict remodeling. However, the two groups had significantly different day-90 BNP level (208.1 ± 263.7 pg/ml vs. 82.4 ± 153.7 pg/ml, P = 0.039) and significantly different 3-month BNP decrease ratios (RBNP13) (14.4 ± 92.2% vs. 69.4 ± 25.9%, P < 0.001). The appropriate cut-off value for RBNP13 was 53.2% (AUC = 0.764, P < 0.001). Early peak CK-MB (cut-off 48.2 ng/ml; AUC = 0.672; P = 0.014) was another independent predictor of remodeling. Additionally, combining peak CK-MB and RBNP13 offered an excellent discrimination for half-year remodeling when assessed by ROC curve (AUC = 0.818, P < 0.001). Conclusion: RBNP13 is a significant independent predictor of 6-month LV remodeling. The early peak CK-MB additionally offered an incremental power to the predictions derived from serial BNP examinations. PMID:28138312

  19. Creatine kinase rate constant in the human heart measured with 3D-localization at 7 tesla.

    Science.gov (United States)

    Clarke, William T; Robson, Matthew D; Neubauer, Stefan; Rodgers, Christopher T

    2017-07-01

    We present a new Bloch-Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first-order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four-angle saturation transfer (FAST) method using amplitude-modulated radiofrequency pulses, phosphorus Bloch-Siegert B1+-mapping to determine the per-voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after (1) H localization). BOAST kfCK values were 0.281 ± 0.002 s(-1) in the calf and 0.35 ± 0.05 s(-1) in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg(-1) s(-1) . The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10-cm loop coil. Magn Reson Med 78:20-32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  20. CK (Creatine Kinase) Test

    Science.gov (United States)

    ... Infections – viral (such as influenza and HIV ), bacterial , fungal , and parasitic (such as malaria ) Connective tissue disorders (e.g. lupus , rheumatoid arthritis ) Celiac disease Renal failure In critically ill patients ...

  1. Elevated creatine kinase does not necessarily correspond temporally with onset of muscle rigidity in neuroleptic malignant syndrome: a report of two cases

    Directory of Open Access Journals (Sweden)

    Nisijima K

    2012-12-01

    Full Text Available Koichi NisijimaDepartment of Psychiatry, Jichi Medical University, Tochigi, JapanAbstract: Neuroleptic malignant syndrome is an uncommon but dangerous complication of antipsychotic drugs, characterized by clinical symptoms that include hyperthermia, severe muscle rigidity, autonomic dysfunction, and altered mental state. Serum creatine kinase (CK elevation occurs in over 90% of cases. Many diagnostic criteria sets for neuroleptic malignant syndrome have been proposed, all of which include hyperthermia and muscle rigidity as major symptoms, and serum CK elevation as either a major or minor symptom. In general, elevated CK occurs in the initial stage of neuroleptic malignant syndrome and corresponds temporally with the onset of muscle rigidity. However, in some exceptional cases, CK elevation and emergence of muscle rigidity do not appear in the same stage, making early diagnosis of neuroleptic malignant syndrome more difficult. Two rare cases of neuroleptic malignant syndrome are presented in which elevated serum CK and emergence of muscle rigidity did not occur in the same stage of neuroleptic malignant syndrome. An elevated CK level is common in the early stage of neuroleptic malignant syndrome, suggesting that serum CK elevation is a useful indicator for early detection of neuroleptic malignant syndrome. However, a definitive diagnosis of neuroleptic malignant syndrome must be determined from the presence of specific clinical symptoms.Keywords: neuroleptic malignant syndrome, creatine kinase, muscle rigidity

  2. Effects of creatine monohydrate supplementation and exercise on depression-like behaviors and raphe 5-HT neurons in mice

    Science.gov (United States)

    Ahn, Nari; Leem, Yea Hyun; Kato, Morimasa; Chang, Hyukki

    2016-01-01

    [Purpose] The effects of creatine and exercise on chronic stress-induced depression are unclear. In the present study, we identified the effects of 4-week supplementation of creatine monohydrate and/or exercise on antidepressant behavior and raphe 5-HT expression in a chronic mild stress-induced depressed mouse model. [Methods] Seven-week-old male C57BL/6 mice (n=48) were divided randomly into 5 groups: (1) non-stress control (CON, n=10), (2) stress control (ST-CON, n=10), (3) stress and creatine intake (ST-Cr, n=10), (4) stress and exercise (ST-Ex, n=9), and (5) combined stress, exercise, and creatine intake (ST-Cr+Ex, n=9). After five weeks’ treatment, we investigated using both anti-behavior tests (the Tail Suspension Test (TST) and the Forced Swimming Test (FST)), and 5-HT expression in the raphe nuclei (the dorsal raphe (DR) and median raphe (MnR)). [Results] Stress for 4 weeks significantly increased depressive behaviors in the mice. Treatment with creatine supplementation combined with exercise significantly decreased depressive behaviors as compared with the CON-ST group in both the TST and FST tests. With stress, 5-HT expression in the raphe nuclei decreased significantly. With combined creatine and exercise, 5-HT positive cells increased significantly and had a synergic effect on both DR and MnR. [Conclusion] The present study found that even a single treatment of creatine or exercise has partial effects as an antidepressant in mice with chronic mild stress-induced depression. Furthermore, combined creatine and exercise has synergic effects and is a more effective prescription than a single treatment.

  3. Implications of automated creatine kinase (CK)-MM1,2,3/CK-MB1,2 isoform analysis as an early marker for the detection of myocardial tissue damage

    NARCIS (Netherlands)

    Swaanenburg, JCJM; Pentinga, M; Dejongste, MJL; Kema, IP

    1996-01-01

    Measurement of creatine kinase (CK) isoforms enables the clinician to detect myocardial tissue damage at an early stage after myocardial infarction. According to the manufacturer's specifications, it should be possible to perform CK isoform analysis automatically using the new Cardio Rep(TM) analyse

  4. Growth inhibition in response to estrogen withdrawal and tamoxifen therapy of human breast cancer xenografts evaluated by in vivo 31P magnetic resonance spectroscopy, creatine kinase activity, and apoptotic index

    DEFF Research Database (Denmark)

    Kristensen, C A; Kristjansen, P E; Brünner, N

    1995-01-01

    index, and creatine kinase (CK) activity. Tumors of each line were grown in ovariectomized nude mice during stimulation from a s.c. 17 beta-estradiol pellet. At a tumor size of approximately 350 mm3, the pellet was removed from one-half of the animals. The remaining one-half served as controls...

  5. Serum concentrations of creatine kinase and of triglycerides during lactation in gilts bred older and in multiparous sows fed ad libitum

    Directory of Open Access Journals (Sweden)

    Nogueira R.H.G.

    2000-01-01

    Full Text Available The aim of this paper was to assess the possible variation in blood concentrations of creatine kinase (CK and triglycerides in gilts bred older in comparison with multiparous sows. Ten primiparous and ten Camborough multiparous sows from the fourth to seventh parities were used. Breeding age and weight of gilts averaged respectively 231 days and 149.5kg. All females were moved into individual farrowing crates and were managed under the same conditions. Blood samples were collected by puncturing the coccygeal artery on day 7 before expected farrowing, and on days 2, 7, 14, 21 of lactation and 2 days after weaning. No difference in triglycerides and CK serum concentrations between groups were observed. The CK levels were low before farrowing, increased substantially on days 2 and 7 and decreased toward the end of lactation. The concentrations of triglycerides were slightly high before the parturition, diminished on days 2, 7, 14 and 21 and increased after weaning.

  6. The Effects of Heart and Skeletal Muscle Inflammation and Cardiomyopathy Syndrome on Creatine Kinase and Lactate Dehydrogenase Levels in Atlantic Salmon (Salmo salar L.

    Directory of Open Access Journals (Sweden)

    Muhammad Naveed Yousaf

    2012-01-01

    Full Text Available Heart and skeletal muscle inflammation (HSMI and cardiomyopathy syndrome (CMS are putative viral cardiac diseases of Atlantic salmon. This study examined the levels and correlated the serum enzymes creatine kinase (CK and lactate dehydrogenase (LDH to the histopathology of clinical outbreaks of HSMI and chronic CMS in farmed Atlantic salmon. A total of 75 fish from 3 different HSMI outbreaks, 30 chronic CMS fish, and 68 fish from 3 nondiseased fish groups were used as the study population (N=173. Serum CK and LDH levels correlated significantly with the total inflammation and total necrosis scores for HSMI fish (P=0.001. However, no correlation was identified for enzyme levels and histopathology scores for chronic CMS fish. The significantly increased CK and LDH levels and their positive correlations to histopathology differentiate HSMI from CMS clinically suggesting the potential use of enzymes for screening for HSMI is promising.

  7. Neuroleptic malignant-like syndrome with a slight elevation of creatine-kinase levels and respiratory failure in a patient with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Wei L

    2014-02-01

    Full Text Available Li Wei,1,2 Yinghui Chen1,2 1Department of Neurology, Jinshan Hospital, 2Department of Neurology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Abstract: Neuroleptic malignant-like syndrome (NMLS is a rare but catastrophic complication of drug treatment for Parkinson's disease (PD. Sudden withdrawal and abrupt reduction of antiparkinsonian drugs are major risk factors. Just as its name suggests, the clinical features of NMLS are similar to neuroleptic malignant syndrome, which is a dangerous adverse response to antipsychotic drugs. Both of these conditions can present with hyperthermia, marked muscle rigidity, altered consciousness, autonomic dysfunction, and elevated serum creatine-kinase (CK levels. However, we describe a special NMLS case with a slight elevation of CK levels and respiratory failure in the full course of her treatment. The patient, a 68-year-old woman with a 4-years history of Parkinson's disease, presented with hyperthermia and severe muscular rigidity. During the course of her treatment, her maximum temperature was extremely high (above 41°C. At the beginning, the diagnosis of NMLS secondary to dopamine decrease was difficult to make, because her initial blood examination revealed that her serum CK levels were mildly elevated and decreased to normal range rapidly. Although antiparkinsonian drugs and supportive treatment were applied, the patient developed an acute respiratory failure in the early course of treatment. This case report highlights that when confronted with Parkinson's patients with high body temperature and muscle rigidity, NMLS should be taken into consideration even if there is no CK elevation. Likewise, the need for supportive care is essential, because its complications are severe, even such as respiratory failure. Keywords: antiparkinsonian drugs, creatine kinase, parkinsonism–hyperpyrexia syndrome, respiratory failure

  8. Creatine biosynthesis and transport in health and disease.

    Science.gov (United States)

    Joncquel-Chevalier Curt, Marie; Voicu, Pia-Manuela; Fontaine, Monique; Dessein, Anne-Frédérique; Porchet, Nicole; Mention-Mulliez, Karine; Dobbelaere, Dries; Soto-Ares, Gustavo; Cheillan, David; Vamecq, Joseph

    2015-12-01

    Creatine is physiologically provided equally by diet and by endogenous synthesis from arginine and glycine with successive involvements of arginine glycine amidinotransferase [AGAT] and guanidinoacetate methyl transferase [GAMT]. A specific plasma membrane transporter, creatine transporter [CRTR] (SLC6A8), further enables cells to incorporate creatine and through uptake of its precursor, guanidinoacetate, also directly contributes to creatine biosynthesis. Breakthrough in the role of creatine has arisen from studies on creatine deficiency disorders. Primary creatine disorders are inherited as autosomal recessive (mutations affecting GATM [for glycine-amidinotransferase, mitochondrial]) and GAMT genes) or X-linked (SLC6A8 gene) traits. They have highlighted the role of creatine in brain functions altered in patients (global developmental delay, intellectual disability, behavioral disorders). Creatine modulates GABAergic and glutamatergic cerebral pathways, presynaptic CRTR (SLC6A8) ensuring re-uptake of synaptic creatine. Secondary creatine disorders, addressing other genes, have stressed the extraordinary imbrication of creatine metabolism with many other cellular pathways. This high dependence on multiple pathways supports creatine as a cellular sensor, to cell methylation and energy status. Creatine biosynthesis consumes 40% of methyl groups produced as S-adenosylmethionine, and creatine uptake is controlled by AMP activated protein kinase, a ubiquitous sensor of energy depletion. Today, creatine is considered as a potential sensor of cell methylation and energy status, a neurotransmitter influencing key (GABAergic and glutamatergic) CNS neurotransmission, therapeutic agent with anaplerotic properties (towards creatine kinases [creatine-creatine phosphate cycle] and creatine neurotransmission), energetic and antioxidant compound (benefits in degenerative diseases through protection against energy depletion and oxidant species) with osmolyte behavior (retention of

  9. Both Creatine and Its Product Phosphocreatine Reduce Oxidative Stress and Afford Neuroprotection in an In Vitro Parkinson’s Model

    Science.gov (United States)

    Martín-de-Saavedra, Maria D.; Romero, Alejandro; Egea, Javier; Ludka, Fabiana K.; Tasca, Carla I.; Farina, Marcelo; Rodrigues, Ana Lúcia S.; López, Manuela G.

    2014-01-01

    Creatine is the substrate for creatine kinase in the synthesis of phosphocreatine (PCr). This energetic system is endowed of antioxidant and neuroprotective properties and plays a pivotal role in brain energy homeostasis. The purpose of this study was to investigate the neuroprotective effect of creatine and PCr against 6-hydroxydopamine (6-OHDA)-induced mitochondrial dysfunction and cell death in rat striatal slices, used as an in vitro Parkinson’s model. The possible involvement of the signaling pathway mediated by phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase-3β (GSK3β) was also evaluated. Exposure of striatal slices to 6-OHDA caused a significant disruption of the cellular homeostasis measured as 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction, lactate dehydrogenase release, and tyrosine hydroxylase levels. 6-OHDA exposure increased the levels of reactive oxygen species and thiobarbituric acid reactive substances production and decreased mitochondrial membrane potential in rat striatal slices. Furthermore, 6-OHDA decreased the phosphorylation of Akt (Serine473) and GSK3β (Serine9). Coincubation with 6-OHDA and creatine or PCr reduced the effects of 6-OHDA toxicity. The protective effect afforded by creatine or PCr against 6-OHDA-induced toxicity was reversed by the PI3K inhibitor LY294002. In conclusion, creatine and PCr minimize oxidative stress in striatum to afford neuroprotection of dopaminergic neurons. PMID:25424428

  10. Both creatine and its product phosphocreatine reduce oxidative stress and afford neuroprotection in an in vitro Parkinson's model.

    Science.gov (United States)

    Cunha, Mauricio Peña; Martín-de-Saavedra, Maria D; Romero, Alejandro; Egea, Javier; Ludka, Fabiana K; Tasca, Carla I; Farina, Marcelo; Rodrigues, Ana Lúcia S; López, Manuela G

    2014-01-01

    Creatine is the substrate for creatine kinase in the synthesis of phosphocreatine (PCr). This energetic system is endowed of antioxidant and neuroprotective properties and plays a pivotal role in brain energy homeostasis. The purpose of this study was to investigate the neuroprotective effect of creatine and PCr against 6-hydroxydopamine (6-OHDA)-induced mitochondrial dysfunction and cell death in rat striatal slices, used as an in vitro Parkinson's model. The possible involvement of the signaling pathway mediated by phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase-3β (GSK3β) was also evaluated. Exposure of striatal slices to 6-OHDA caused a significant disruption of the cellular homeostasis measured as 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction, lactate dehydrogenase release, and tyrosine hydroxylase levels. 6-OHDA exposure increased the levels of reactive oxygen species and thiobarbituric acid reactive substances production and decreased mitochondrial membrane potential in rat striatal slices. Furthermore, 6-OHDA decreased the phosphorylation of Akt (Serine(473)) and GSK3β (Serine(9)). Coincubation with 6-OHDA and creatine or PCr reduced the effects of 6-OHDA toxicity. The protective effect afforded by creatine or PCr against 6-OHDA-induced toxicity was reversed by the PI3K inhibitor LY294002. In conclusion, creatine and PCr minimize oxidative stress in striatum to afford neuroprotection of dopaminergic neurons.

  11. In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.

    Science.gov (United States)

    Cui, Min-Hui; Jayalakshmi, Kamaiah; Liu, Laibin; Guha, Chandan; Branch, Craig A

    2015-12-01

    Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use of in vivo (31)P MRSI of creatine kinase (CK)-expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by (1)H MRS suffers from low signal-to-noise ratio (SNR). We examine the possibility of using the Cr analog cyclocreatine (CCr, a substrate for CK), which is quickly phosphorylated to phosphocyclocreatine (PCCr), as a higher SNR alternative to Cr. (1)H MRS and (31)P MRSI were employed to measure the effect of incremental supplementation of CCr upon PCCr, γ-ATP, pH and Pi /ATP in the liver of transgenic mice expressing the BB isoform of CK (CKBB) in hepatocytes. Water supplementation with 0.1% CCr led to a peak total PCCr level of 17.15 ± 1.07 mmol/kg wet weight by 6 weeks, while adding 1.0% CCr led to a stable PCCr liver level of 18.12 ± 3.91 mmol/kg by the fourth day of feeding. PCCr was positively correlated with CCr, and ATP concentration and pH declined with increasing PCCr. Feeding with 1% CCr in water induced an apparent saturated level of PCCr, suggesting that CCr quantization may not be necessary for quantifying expression of CK in mice. These findings support the possibility of using (31)P MRS to noninvasively monitor hepatocyte transplant success with CK-expressing hepatocytes.

  12. Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?

    Science.gov (United States)

    Wyss, Markus; Schulze, Andreas

    2002-01-01

    Major achievements made over the last several years have highlighted the important roles of creatine and the creatine kinase reaction in health and disease. Inborn errors of metabolism have been identified in the three main steps involved in creatine metabolism: arginine:glycine amidinotransferase (AGAT), S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase (GAMT), and the creatine transporter. All these diseases are characterized by a lack of creatine and phosphorylcreatine in the brain, and by (severe) mental retardation. Similarly, knockout mice lacking the brain cytosolic and mitochondrial isoenzymes of creatine kinase displayed a slightly increased creatine concentration, but no phosphorylcreatine in the brain. These mice revealed decreased weight gain and reduced life expectancy, disturbed fat metabolism, behavioral abnormalities and impaired learning capacity. Oral creatine supplementation improved the clinical symptoms in both AGAT and GAMT deficiency, but not in creatine transporter deficiency. In addition, creatine supplementation displayed neuroprotective effects in several animal models of neurological disease, such as Huntington's disease, Parkinson's disease, or amyotrophic lateral sclerosis. All these findings pinpoint to a close correlation between the functional capacity of the creatine kinase/phosphorylcreatine/creatine system and proper brain function. They also offer a starting-point for novel means of delaying neurodegenerative disease, and/or for strengthening memory function and intellectual capabilities.Finally, creatine biosynthesis has been postulated as a major effector of homocysteine concentration in the plasma, which has been identified as an independent graded risk factor for atherosclerotic disease. By decreasing homocysteine production, oral creatine supplementation may, thus, also lower the risk for developing, e.g., coronary heart disease or cerebrovascular disease. Although compelling, these results require further

  13. Analysis of the Causes of Mental Illness of Creatine Kinase in Patients with Increased%精神病患者血清肌酸激酶增高探讨

    Institute of Scientific and Technical Information of China (English)

    张文亮

    2015-01-01

    目的探讨住院精神疾病患者出现的血清高水平肌酸激酶(CK)活性的机制。方法对2013年1~10月住院精神疾病患者血清肌酸激酶检测值大于800 U/L病例资料进行统计分析。结果出现肌酸激酶检测值大于800 U/L病例375例,平均值为1384 U/L,诊断以精神分裂症和双相障碍为主。结论精神疾病患者血清肌酸激酶活性存在不同程度的增高,可能与精神疾病的某些症状有关联。%Objective To investigate the hospital patients with mental disease high levels of serum creatine kinase (CK) activity mechanism. Methods 2013.1~ 2013.10 month of hospitalization in patients with mental disorders in detection of serum creatine kinase values greater than 800 U/L were col ected and statistical analysis. Results The emergence of creatine kinase detection value is greater than 800 U/L in 375 cases, the average value is 1384 U/L, diagnosed with schizophrenia and bipolar disorder based. Conclusion The patients with mental disorders of serum creatine kinase activity has increased in dif erent degrees, may be associated with some symptoms of mental il ness.

  14. Taurine chloramine is more selective than hypochlorous acid at targeting critical cysteines and inactivating creatine kinase and glyceraldehyde-3-phosphate dehydrogenase.

    Science.gov (United States)

    Peskin, Alexander V; Winterbourn, Christine C

    2006-01-01

    Hypochlorous acid (HOCl) and chloramines are produced by the neutrophil enzyme, myeloperoxidase. Both react readily with thiols, although chloramines differ from HOCl in discriminating between low molecular weight thiols on the basis of their pKa. Here, we have compared the reactivity of HOCl and taurine chloramine with thiol proteins by examining inactivation of creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). With both enzymes, loss of activity paralleled thiol loss. For CK both were complete at a 1:1 taurine chloramine:thiol mole ratio. For GAPDH each chloramine oxidized two thiols. Three times more HOCl than taurine chloramine was required for inactivation, indicating that HOCl is less thiol specific. Competition studies showed that thiols of CK were 4 times more reactive with taurine chloramine than thiols of GAPDH (rate constants of 1200 and 300 M-1s-1 respectively). These compare with 205 M-1s-1 for cysteine and are consistent with their lower pKa's. Both enzymes were equally susceptible to HOCl. GSH competed directly with the enzyme thiols for taurine chloramine and protected against oxidative inactivation. At lower GSH concentrations, mixed disulfides were formed. We propose that chloramines should preferentially attack proteins with low pKa thiols and this could be important in regulatory processes.

  15. A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4.

    Science.gov (United States)

    Dwianingsih, Ery Kus; Takeshima, Yasuhiro; Itoh, Kyoko; Yamauchi, Yumiko; Awano, Hiroyuki; Malueka, Rusdy Ghazali; Nishida, Atsushi; Ota, Mitsunori; Yagi, Mariko; Matsuo, Masafumi

    2010-01-01

    Congenital generalized lipodystrophy (CGL), characterized by generalized absence of adipose tissue, has heterogeneous causes. Recently, a novel type of CGL complicated by muscular dystrophy was categorized as CGL4 caused by PTRF-CAVIN deficiency. However, it is unknown whether CGL4 exhibits clinical abnormalities during the infantile period. Here, we describe the youngest Japanese case of CGL4-a Japanese girl with asymptomatic high serum creatine kinase (CK) levels at 3months old. She was referred to our hospital at 5months of age because of her elevated serum CK (2528IU/L). Generalized absence of adipose tissue was first recognized at 2years of age. Mutation analysis of genes known to be responsible for CGL1-3 failed to disclose any abnormalities. Instead, analysis of the PTRF-CAVIN gene encoding PTRF-CAVIN revealed compound heterozygous mutations, one allele contained an insertion (c.696_697insC) and the other allele harbored a novel nonsense mutation (c.512C>A). Our patient had low serum leptin and adiponectin levels and insulin resistance. Pathological studies on biopsied muscle disclosed mild dystrophic change and highly reduced expression of PTRF-CAVIN. It was concluded that our PTRF-CAVIN deficient patient showed not only CGL but also asymptomatic elevation of serum CK because of her mild muscle dystrophic change. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Optimized preservation of isoforms of creatine kinase MM isoenzyme in plasma specimens and their rapid quantification by semi-automated chromatofocusing.

    Science.gov (United States)

    Abendschein, D R; Fontanet, H L; Nohara, R

    1990-05-01

    We report a convenient chromatofocusing procedure for rapid and sensitive quantification of isoforms of the MM isoenzyme of creatine kinase (EC 2.7.3.2) in plasma and efficient methods for preserving isoform profiles during handling of specimens. The assay involves use of prepacked, re-usable Mono P chromatofocusing columns and a "Fast Protein Liquid Chromatograph" (FPLC) system with on-line detection of isoform enzymatic activity in column effluent. Profiles of isoforms are analyzed within 25 min with the use of a 1-mL column; the lower limit of sensitivity for CK activity is 5 mU, and recovery of each isoform is within 1% of the amount added to plasma. Collection of blood specimens in Vacutainer Tubes containing 28.5 mumol of EDTA (final concentration in plasma, 7 to 10 mmol/L) inhibited carboxypeptidase activity in plasma by 76%, sufficient to essentially abolish isoform conversion in vitro at room temperature. These methods should facilitate applications of isoform analysis for diagnosis of myocardial infarction and coronary artery recanalization.

  17. N-Acetylcysteine Supplementation Controls Total Antioxidant Capacity, Creatine Kinase, Lactate, and Tumor Necrotic Factor-Alpha against Oxidative Stress Induced by Graded Exercise in Sedentary Men

    Directory of Open Access Journals (Sweden)

    Donrawee Leelarungrayub

    2011-01-01

    Full Text Available Aim of this study was to evaluate the effects of short-term (7 days N-acetylcysteine (NAC at 1,200 mg daily supplementation on muscle fatigue, maximal oxygen uptake (VO2max, total antioxidant capacity (TAC, lactate, creatine kinase (CK, and tumor necrotic factor-alpha (TNF-α. Twenty-nine sedentary men (13 controls; 16 in the supplement group from a randomized control were included. At before and after supplementation, fatigue index (FI was evaluated in the quadriceps muscle, and performed a graded exercise treadmill test to induce oxidative stress, and as a measure of VO2max. Blood samples were taken before exercise and 20 minutes after it at before and after supplementation, to determine TAC, CK, lactate, and TNF-α levels. Results showed that FI and VO2max increased significantly in the supplement group. After exercise decreased the levels of TAC and increased lactate, CK, and TNF-α of both groups at before supplementation. After supplementation, lactate, CK, and TNF-α levels significantly increased and TAC decreased after exercise in the control group. Whereas the TAC and lactate levels did not change significantly, but CK and TNF-α increased significantly in the supplement group. Therefore, this results showed that NAC improved the muscle fatigue, VO2max, maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

  18. Effects of Sesame (Sesamum indicum L.) Supplementation on Creatine Kinase, Lactate Dehydrogenase, Oxidative Stress Markers, and Aerobic Capacity in Semi-Professional Soccer Players.

    Science.gov (United States)

    Barbosa, Carlos V da Silva; Silva, Alexandre S; de Oliveira, Caio V C; Massa, Nayara M L; de Sousa, Yasmim R F; da Costa, Whyara K A; Silva, Ayice C; Delatorre, Plínio; Carvalho, Rhayane; Braga, Valdir de Andrade; Magnani, Marciane

    2017-01-01

    Nutritional intervention with antioxidants rich foods has been considered a strategy to minimize the effects of overtraining in athletes. This experimental, randomized, and placebo-controlled study evaluated the effects of consumption of sesame (Sesamum indicum L.) on muscle damage markers, oxidative stress, systemic inflammation, and aerobic performance in male semi-professional soccer players. Twenty athletes were randomly assigned to groups that received 40 g (two tablespoons) per day of sesame or a placebo during 28 days of regular training (exposed to routine training that includes loads of heavy training in the final half of the season). Before and after intervention, creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), C-reactive protein (hs-CRP), and aerobic capacity were evaluated. Before intervention, a physiologic imbalance was noted in both groups related to CK and LDH levels. Sesame intake caused a reduction of CK (19%, p sesame consumption may reduce muscle damage and oxidative stress while improving the aerobic capacity in soccer players.

  19. Ischemia-modified albumin is not better than creatine kinase-MB and cardiac troponin I in predicting a cardiac injury in nontraumatic subarachnoid hemorrhage.

    Science.gov (United States)

    Baydin, Ahmet; Amanvermez, Ramazan; Tuncel, Özgür Korhan; Ocak, Metin; Meric, Murat; Cokluk, Cengiz

    2015-04-01

    The aims were to investigate the role of serum ischemia-modified albumin (IMA), tumor necrosis factor α (TNF-α), and myeloperoxidase (MPO) and to evaluate the relationship between IMA and cardiac markers (creatine kinase myocardial isoenzyme [CK-MB] and cardiac troponin I [cTnI]) related to cardiac abnormalities in adult patients after nontraumatic subarachnoid hemorrhage (SAH). Twenty-nine patients with nontraumatic SAH admitted to the emergency department and 20 healthy adults as the control group were included in the study. Ischemia-modified albumin, TNF-α, MPO, CK-MB, cTnI, and leukocyte count (white blood cell [WBC]) in the circulation were measured on admission. Ischemia-modified albumin, TNF-α, and MPO levels were higher by mean values of 11.6%, 9.5%, and 2.9%, respectively, in patients with SAH compared with control group. However, levels of these parameters were not statistically different between the groups (P > .05). However, WBC, CK-MB, and cTnI values were significantly higher in patients with SAH compared with healthy control (P MB, and cTnI tests to differentiate between patients after SAH and controls according to receiver operating characteristic curve. The results suggest that IMA is not better than CK-MB and cTnI in predicting a cardiac injury in patients after nontraumatic SAH. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Interrelationship of rotavirus infection and Creatine Kinase-MB isoenzyme levels in children hospitalized with acute gastroenteritis in Guangzhou, China, 2012-2015.

    Science.gov (United States)

    Zheng, Jianbin; Zheng, Haiqing; Gupta, Ramit Kumar; Li, Huixian; Shi, Hui; Pan, Liyan; Gong, Sitang; Liang, Huiying

    2017-08-09

    Elevated levels of Creatine Kinase-MB (CK-MB) Isoenzyme are a common phenomenon among rotavirus (RV) diarrhea. However, few studies have addressed this issue using large sample size. In current study, 1,118 children (age MB and its relationship with RV-infection were analyzed and characterized. Multivariate linear regression models showed that RV-positive cases had a 28% rise in CK-MB compared to RV-negative cases (OR = 1.28, 95% CI: 1.15 to 1.41, P MB level of RV-positive group started to rise immediately at the 1(st) day of diarrhea, reached the peak on days 2 to 4, declined during 4-9 days, and then reached a relatively stable level when compared to the RV-negative group. Mediation analyses showed that indirect effect of RV infection on the increase of CK-MB via Vesikari score was significant (β = 8.01, P MB value is a common finding in RV-infection and completely mediated by the severity of diarrhea. CK-MB monitoring may help to identify children with more severe viral infection.

  1. Protection from procedural myocardial injury by omega-3 polyunsaturated fatty acids (PUFAs): is related with lower levels of creatine kinase-MB (CK-MB) and troponin I?

    Science.gov (United States)

    Foroughinia, Farzaneh; Salamzadeh, Jamshid; Namazi, Mohammad H

    2013-10-01

    This study sought to investigate the effect of omega-3 polyunsaturated fatty acids (PUFAs) on cardiac biomarkers, CK-MB, and troponin I in patients undergoing PCI. Restenosis remains as a major long-term complication following percutaneous coronary intervention (PCI). It appears that there is strong relationship between post-PCI creatine kinase-MB (CK-MB) and troponin I elevation and cardiovascular events after PCI. In this randomized clinical trial, a total of 90 patients planned to undergo PCI were randomly assigned into two groups: Group A-receiving omega-3 PUFAs (3 g, 12 h before PCI) plus standard treatment (n = 43) and Group B-control group, receiving only standard therapy (n = 47). Standard treatment included aspirin 325 mg and clopidogrel 600 mg loading dose. The plasma CK-MB level was measured before the procedure (baseline), at 8 and 24 h after PCI. The plasma troponin I was measured at baseline and 24 h after PCI. In comparison with control, omega-3 PUFAs could significantly reduce the level of CK-MB in 8 (P = 0.001) and 24 h (P = 0.012) after its prescription in the omega-3 PUFAs group. Omega-3 PUFAs could not significantly decrease troponin I. Our results revealed that omega-3 PUFAs can be considered as a safe adjunctive medication to the standard regimen before PCI for the aim of decreasing cardiovascular event after PCI. © 2012 John Wiley & Sons Ltd.

  2. PREDICTION OF HIE BY NUCLEATED RBC’S IN CORD BLOOD, SERUM CREATINE KINASE AND ASSESSMENT OF OUTCOME BY FOLLOW UP UPTO 6 MONTHS

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    Shivaprakash

    2013-05-01

    Full Text Available ABSTRACT: OBJECTIVES: Birth asphyxia is the most common cause of preventa ble cerebral injury occurring in the neonatal period and contributes si gnificantly to neonatal morbidity and mortality. This study was conducted to predict the occurrence of HIE by nucleated Red blood cells and creatinine kinase in cord blood of asphyxiated babi es and assessment of outcome by follow up upto 6 months. MATERIALS AND METHODS : Study was conducted on 50 neonates comprising the cases and 50 neonates comprising the controls born in Adi chunchanagiri Institute of Medical Sciences and Research Centre, B.G. Nagara from January 2011 to June 2012.. The cord blood samples for CK and nucleated RBCs was drawn at the time of birth a nd sent for analysis. Anthropometry was done at Birth ,1st month,3rd month and 6th month(final v isit , developmental assessment using DASII along with anthropometric measurements was done. RESULTS: The cut-off CK value of 450 U/ L has 91.3% sensitivity with a specificity of 96.3% & has a positive predictive value of 95.49 with a negative predictive value of 92.85 .The cut-off Nuc leated RBCs value of >6 has 93.48% sensitivity with a specificity of 96.3% & has a positive predic tive value of 97.7 % with a negative predictive value of 94.64%. NRBCs have more diagnostic value t han CK with more Area Under ROC value when compared (0.989 vs. 0.986. On follow up, in the final visit, 8 cases had motor delay and 7 cases had mental delay against no developmental del ay in controls. CONCLUSION : Prediction of HIE in the asphyxiated cases can be done using the cord blood NRBCs and Creatine kinase, & suitable interventions and intensive monitoring can be plann ed thereby helping in identifying the high risk cases

  3. Augmentation of Creatine in the Heart.

    Science.gov (United States)

    Zervou, Sevasti; Whittington, Hannah J; Russell, Angela J; Lygate, Craig A

    2016-01-01

    Creatine is a principle component of the creatine kinase (CK) phosphagen system common to all vertebrates. It is found in excitable cells, such as cardiomyocytes, where it plays an important role in the buffering and transport of chemical energy to ensure that supply meets the dynamic demands of the heart. Multiple components of the CK system, including intracellular creatine levels, are reduced in heart failure, while ischaemia and hypoxia represent acute crises of energy provision. Elevation of myocardial creatine levels has therefore been suggested as potentially beneficial, however, achieving this goal is not trivial. This mini-review outlines the evidence in support of creatine elevation and critically examines the pharmacological approaches that are currently available. In particular, dietary creatine-supplementation does not sufficiently elevate creatine levels in the heart due to subsequent down-regulation of the plasma membrane creatine transporter (CrT). Attempts to increase passive diffusion and bypass the CrT, e.g. via creatine esters, have yet to be tested in the heart. However, studies in mice with genetic overexpression of the CrT demonstrate proof-of-principle that elevated creatine protects the heart from ischaemia-reperfusion injury. This suggests activation of the CrT as a major unmet pharmacological target. However, translation of this finding to the clinic will require a greater understanding of CrT regulation in health and disease and the development of small molecule activators.

  4. Relationship of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and proteinuria to cardiomyopathy in the owl monkey (Aotus vociferans)

    Energy Technology Data Exchange (ETDEWEB)

    Gozalo, Alfonso S.; Chavera, Alfonso; Montoya, Enrique J.; Takano, Juan; Weller, Richard E.

    2008-02-01

    The purpose of this study was to determine serum reference values for crea- tine kinase (CK), aspartate aminotransferase (AST), and lactate dehydroge- nase (LDH) in captive-born and wild-caught owl monkeys to assess their usefulness for diagnosing myocardial disease. Urine samples were also collected and semi-quantitative tests performed. There was no statistically significant difference between CK, AST, and LDH when comparing both groups. However, when comparing monkeys with proteinuria to those without proteinuria, a statistically significant difference in CK value was observed (P = 0.021). In addition, the CK/AST ratio revealed that 29% of the animals included in this study had values suggesting cardiac infarction. Grossly, cardiac concentric hypertrophy of the left ventricle and small, pitted kidneys were the most common findings. Microscopically, myocardial fibrosis, contraction band necrosis, hypertrophy and hyperplasia of coronary arteries, medium-sized renal arteries, and afferent glomerular arteriolae were the most significant lesions, along with increased mesangial matrix and hypercellularity of glomeruli, Bowman’s capsule, and peritubular space fibroplasia. These findings suggest that CK, AST, and LDH along with urinalysis provide a reliable method for diagnosing cardiomyopathies in the owl monkey. In addition, CK/AST ratio, proteinuria, and the observed histological and ultrastructural changes suggest that Aotus vociferans suffer from arterial hypertension and chronic myocardial infarction.

  5. Light-emitting diode therapy (LEDT) before matches prevents increase in creatine kinase with a light dose response in volleyball players.

    Science.gov (United States)

    Ferraresi, Cleber; Dos Santos, Ricardo Vinicius; Marques, Guilherme; Zangrande, Marcelo; Leonaldo, Roberley; Hamblin, Michael R; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio

    2015-05-01

    Low-level laser (light) therapy (LLLT) has been applied over skeletal muscles before intense exercise (muscular pre-conditioning) in order to reduce fatigue and muscle damage (measured by creatine kinase, CK) in clinical trials. However, previous exercise protocols do not exactly simulate the real muscle demand required in sports. For this reason, the aim of this randomized and double-blind placebo-controlled trial was to investigate whether light-emitting diode therapy (LEDT) applied over the quadriceps femoris muscles, hamstrings, and triceps surae of volleyball players before official matches could prevent muscle damage (CK) with a dose response, establishing a therapeutic window. A professional male volleyball team (12 athletes) was enrolled in this study, and LEDT was applied before 4 matches during a national championship. LEDT used an array of 200 light-emitting diodes (LEDs) arranged in 25 clusters of 4 infrared LEDs (850 ± 20 nm; 130 mW) and 25 clusters of 4 red LEDs (630 ± 10 nm; 80 mW). Athletes were randomized to receive one of four different total doses over each muscle group in a double-blind protocol: 105 J (20 s), 210 J (40 s), 315 J (60 s), and placebo (no light for 30 s). CK in blood was assessed 1 h before and 24 h after each match. LEDT at 210 J avoided significant increases in CK (+10 %; P = 0.993) as well as 315 J (+31 %, P = 0.407). Placebo (0 J) allowed a significant increase in CK (+53 %; P = 0.012) as well as LEDT at 105 J (+59 %; P = 0.001). LEDT prevented significant increases of CK in blood in athletes when applied before official matches with a light dose response of 210-315 J, suggesting athletes might consider applying LEDT before competition.

  6. A membrane-associated adenylate cyclase modulates lactate dehydrogenase and creatine kinase activities required for bull sperm capacitation induced by hyaluronic acid.

    Science.gov (United States)

    Fernández, Silvina; Córdoba, Mariana

    2017-04-01

    Hyaluronic acid, as well as heparin, is a glycosaminoglycan present in the female genital tract of cattle. The aim of this study was to evaluate oxidative metabolism and intracellular signals mediated by a membrane-associated adenylate cyclase (mAC), in sperm capacitation with hyaluronic acid and heparin, in cryopreserved bull sperm. The mAC inhibitor, 2',5'-dideoxyadenosine, was used in the present study. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration were determined spectrophotometrically in the incubation medium. Capacitation and acrosome reaction were evaluated by chlortetracycline technique, while plasma membrane and acrosome integrity were determined by trypan blue stain/differential interference contrast microscopy. Heparin capacitated samples had a significant decrease in LDH and CK activities, while in hyaluronic acid capacitated samples LDH and CK activities both increased compared to control samples, in heparin and hyaluronic acid capacitation conditions, respectively. A significant increase in lactate concentration in the incubation medium occurred in hyaluronic acid-treated sperm samples compared to heparin treatment, indicating this energetic metabolite is produced during capacitation. The LDH and CK enzyme activities and lactate concentrations in the incubation medium were decreased with 2',5'-dideoxyadenosine treatment in hyaluronic acid samples. The mAC inhibitor significantly inhibited heparin-induced capacitation of sperm cells, but did not completely inhibit hyaluronic acid capacitation. Therefore, hyaluronic acid and heparin are physiological glycosaminoglycans capable of inducing in vitro capacitation in cryopreserved bull sperm, stimulating different enzymatic pathways and intracellular signals modulated by a mAC. Hyaluronic acid induces sperm capacitation involving LDH and CK activities, thereby reducing oxidative metabolism, and this process is mediated by mAC.

  7. Glycogen phosphorylase isoenzyme BB, creatine kinase isoenzyme MB and troponin I for monitoring patients with percutaneous coronary intervention - a pilot study.

    Science.gov (United States)

    Skitek, Milan; Kranjec, Igor; Jerin, Aleš

    2014-02-01

    The glycogen phosphorylase isoenzyme BB (GPBB), as an ischemic marker, has not yet been investigated after elective percutaneous coronary intervention (PCI). ose aim of the study was to monitor GPBB, creatine kinase myocardial isoform (CK-MB) mass) and troponin I (TnI) value after PCI in correlation with ischemic incidents. Forty-two consecutive patients undergoing elective PCI were included in the study. Baseline blood samples and two more after the PCI (3 and 24 hours) were taken. The significance of cardiac markers in twenty-ththe stable patients with baseline values of CK-MB mass and TnI below the upper reference limit (URL) was evaluated based on ischemic incidents after PCI. TnI value was the only biomarker that was statistically significant at 3 and 24 hours after PCI in group of 23 stable patients. An overall comparisonthe biomarkers of 18 patients without and five patients with ischemic incidents displayed significant differences only for the baseline GPBB (p=0.019) and CK-MB mass 24 hours after PCI (p=0.034). Ischemic incidents were independently predictable only based on overall CK-MB mass measurements (OR=1.680, p=0.041) and particularly GPBB at baseline (OR=1.899, p=0.008) and CK-MB mass 24 hours after PCI (OR=2.111, p=0.022). Only significant increases in TnI were observed after elective PCI with ischemic incidents predicted using GPBB and CK-MB mass measurements.

  8. Prognostic implications of creatine kinase-MB measurements in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

    Science.gov (United States)

    Bagai, Akshay; Schulte, Phillip J; Granger, Christopher B; Mahaffey, Kenneth W; Christenson, Robert H; Bell, Gregory; Lopes, Renato D; Green, Cynthia L; Lincoff, A Michael; Armstrong, Paul W; Roe, Matthew T

    2014-10-01

    Peak creatine kinase (CK)-MB concentration is related to reperfusion success and clinical outcomes after fibrinolytic therapy for acute myocardial infarction. However, prognostic implications of CK-MB measurements after primary percutaneous coronary intervention (PCI), which provides more predictable and consistent reperfusion, are unknown. We pooled 2,042 primary PCI-treated ST-segment elevation myocardial infarction (STEMI) patients from 3 trials with serial core laboratory-determined CK-MB measurements; 1,799 patients (88.1%) who survived to 36 hours and had ≥4 CK-MB measurements were studied. Cox regression modeling was performed to quantify the association between peak CK-MB concentration (and area under the time-concentration curve [AUC]) and mortality at 6 months, and death or congestive heart failure at 90 days. The median (25th-75th percentiles) peak CK-MB concentration and AUC measurement through 36 hours were 239 (109-429) ng/mL and 4,263 (2,081-7,124) ng/(mL h), respectively. By multivariable analysis, peak CK-MB concentration and AUC measurement were independently associated with 6-month mortality (adjusted hazard ratio [HR] 1.15, 95% CI 1.05-1.25, per 100-ng/mL increase, P = .002; and adjusted HR 1.09, 95% CI 1.03-1.14, per 1,000-ng/[mL h] increase, P MB concentration and AUC measurement are independent predictors of 3- to 6-month cardiovascular outcomes in primary PCI-treated STEMI patients. Our findings guide application of these measurements as efficacy end points in early-phase studies evaluating new therapies for STEMI. Copyright © 2014 Mosby, Inc. All rights reserved.

  9. Development and Evaluation of a New Creatine Kinase MB Mass Determination Assay Using a Latex Agglutination Turbidimetric Immunoassay with an Automated Analyzer.

    Science.gov (United States)

    Hoshino, Tadashi; Hanai, Kazuma; Tanimoto, Kazuhito; Nakayama, Tomohiro

    2016-01-01

    The diagnosis of myocardial infraction (MI) in patients presenting to the emergency department represents a clinical challenge. It is known that creatine kinase-MB isoenzyme (CK-MB) is present in soluble cell fractions of cardiac muscle, and injury to those cells results in an increase of CK-MB in the blood. Therefore, CK-MB is a suitable clinical biomarker of myocardial infraction. To measure CK-MB mass rapidly and easily, we developed the new reagent 'L-type Wako CK-MB mass' (L-CK-MB mass) for the latex agglutination turbidimetric immunoassay method. Using a Hitachi LABOSPECT 008, we evaluated the performance of this assay as a method for quantifying CK-MB mass, and we compared the measurement of the serum CK-MB mass concentration with this assay to that obtained using an electrochemiluminescence immunoassay (ECLIA). A dilution test showed linearity from 5 μg/L to 190 μg/L, and the limit of quantification of the L-CK-MB mass assay was 3.0 μg/L. The within-run CV and between-day CV were 1.0 - 4.5% and 1.8 - 4.4%, respectively. Serum CK-MB mass concentration determined using the L-CK-MB mass assay was reliably and strongly correlated with that determined using ECLIA (n = 163, r = 0.999, y = 0.977x + 0.307). The L-CK-MB mass assay is able to specifically determine CK-MB mass and is a very useful method for the accurate measurement of CK-MB mass for routine clinical analyses.

  10. Stimulation of protein kinase C recruits covert calcium channels in Aplysia bag cell neurons.

    Science.gov (United States)

    Strong, J A; Fox, A P; Tsien, R W; Kaczmarek, L K

    The modulation of voltage-activated calcium currents by protein kinases provides excitable cells with a mechanism for regulating their electrical behaviour. At the single channel level, modulation of calcium current has, to date, been characterized only in cardiac muscle, where beta-adrenergic agonists, acting through cyclic AMP-dependent protein kinase, enhance the calcium current by increasing channel availability and opening. We now report that enhancement of calcium current in the peptidergic bag cell neurons of Aplysia by protein kinase C occurs through a different mechanism, the recruitment of a previously covert class of calcium channel. Under control conditions, bag cell neurons contain only one class of voltage-activated calcium channel with a conductance of approximately 12 pS. After exposure to agents that activate protein kinase C, these neurons also express a second class of calcium channel with a different unitary conductance (approximately 24 pS) that is never seen in untreated cells.

  11. LINGO-1 receptor promotes neuronal apoptosis by inhibiting WNK3 kinase activity.

    Science.gov (United States)

    Zhang, Zhaohuan; Xu, Xiaohui; Xiang, Zhenghua; Yu, Zhongwang; Feng, Jifeng; He, Cheng

    2013-04-26

    LINGO-1 is a functional component of the Nogo receptor 1 · p75(NTR) · LINGO-1 and Nogo receptor 1 · TAJ (TNFRSF19/TROY)·LINGO-1 signaling complexes. It has recently been shown that LINGO-1 antagonists significantly improve neuronal survival after neural injury. However, the mechanism by which LINGO-1 signaling influences susceptibility to apoptosis remains unknown. In an effort to better understand how LINGO-1 regulates these signaling pathways, we used an established model of serum deprivation (SD) to induce neuronal apoptosis. We demonstrate that treatment either with a construct containing the intracellular domain of LINGO-1 or with Nogo66, a LINGO-1 receptor complex agonist, resulted in an enhanced rate of apoptosis in primary cultured cortical neurons under SD. Reducing the expression levels of the serine/threonine kinase WNK3 using shRNA or inhibiting its kinase activity had similar effects on the survival of serum-deprived neurons. Consistent with these observations, we found that LINGO-1 and WNK3 co-localized and co-precipitated in cultured cortical neurons and brain tissue. Significantly, this co-association was enhanced by Nogo66 treatment. Binding of WNK3 to the intracellular domain of LINGO-1 led to a reduction in WNK3 kinase activity, as did Nogo66 stimulation. Moreover, in vitro and in vivo evidence indicates that endogenous WNK3 suppresses SD-induced neuronal apoptosis in a kinase-dependent manner, as the expression of either a WNK3 RNAi construct or a kinase-dead N-terminal fragment of WNK3 led to increased apoptosis. Taken together, our results show that LINGO-1 potentiates neuronal apoptosis, likely by inhibiting WNK3 kinase activity.

  12. The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis.

    Science.gov (United States)

    Xu, Z; Maroney, A C; Dobrzanski, P; Kukekov, N V; Greene, L A

    2001-07-01

    Neuronal apoptotic death induced by nerve growth factor (NGF) deprivation is reported to be in part mediated through a pathway that includes Rac1 and Cdc42, mitogen-activated protein kinase kinases 4 and 7 (MKK4 and -7), c-Jun N-terminal kinases (JNKs), and c-Jun. However, additional components of the pathway remain to be defined. We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling. Overexpression of MLKs effectively induces apoptotic death of cultured neuronal PC12 cells and sympathetic neurons, while expression of dominant-negative forms of MLKs suppresses death evoked by NGF deprivation or expression of activated forms of Rac1 and Cdc42. CEP-1347 (KT7515), which blocks neuronal death caused by NGF deprivation and a variety of additional apoptotic stimuli and which selectively inhibits the activities of MLKs, effectively protects neuronal PC12 cells from death induced by overexpression of MLK family members. In addition, NGF deprivation or UV irradiation leads to an increase in both level and phosphorylation of endogenous DLK. These observations support a role for MLKs in the neuronal death mechanism. With respect to ordering the death pathway, dominant-negative forms of MKK4 and -7 and c-Jun are protective against death induced by MLK overexpression, placing MLKs upstream of these kinases. Additional findings place the MLKs upstream of mitochondrial cytochrome c release and caspase activation.

  13. Creatine kinase elevation caused by a combination of fluvastatin and telmisartan in a patient heterozygous for the CYP2C9*3 and ABCC2 -24C > T variants: a case report.

    Science.gov (United States)

    Meyer zu Schwabedissen, Henriette E; Siegmund, Werner; Kroemer, Heyo K; Rollnik, Jens D

    2014-10-03

    Genetic factors as predictor of the individual outcome of drug therapy is one aim of personalized medicine approaches. We report a drug metabolism based analysis of genetic polymorphisms in a Caucasian patient receiving fluvastatin and telmisartan experiencing myotoxicity (myalgia and moderate creatine kinase elevation). The obtained findings suggest that heterocygocity of cytochrome P450 CYP2C9*3 variant in combination with multidrug resistance-associated protein MRP2-24C > T functions as risk factor predisposing to experience drug-drug interaction combing those drugs.

  14. Ins(1,4,5)P{sub 3} facilitates ATP accumulation via phosphocreatine/creatine kinase in the endoplasmic reticulum extracted from MDCK cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jing [Medical Research Center, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Department of Dental Implantology, School of Stomatology, Tongji University, Shanghai 200072 (China); Ogata, Shigenori [Joint Laboratory for Frontier Medical Science, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Segawa, Masaru [Central Laboratory for Pathology and Morphology, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Usune, Sadaharu [Research Laboratory of Biodynamics, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Zhao, Yumei [Department of Pediatric Dentistry, School of Dentistry of Shanghai Tongji University, Shanghai 200072 (China); Katsuragi, Takeshi, E-mail: katsurag@fukuoka-u.ac.jp [Medical Research Center, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan)

    2010-07-02

    So far, the content and accumulation of ATP in isolated endoplasmic reticulum (ER) are little understood. First, we confirmed using electron microscopic and Western blotting techniques that the samples extracted from MDCK cells are endoplasmic reticulum (ER). The amounts of ATP in the extracted ER were measured from the filtrate after a spinning down of ultrafiltration spin column packed with ER. When the ER sample (5 {mu}g) after 3 days freezing was suspended in intracellular medium (ICM), 0.1% Triton X and ultrapure water (UPW), ATP amounts from the ER with UPW were the highest and over 10 times compared with that from the control with ICM, indicating that UPW is the most effective tool in destroying the ER membrane. After a 10-min-incubation with ICM containing phosphocreatine (PCr)/creatine kinase (CK) of the fresh ER. ATP amounts in the filtrate obtained by spinning down were not changed from that in the control (no PCr/CK). However, ATP amounts in the filtrate from the second spinning down of the ER (treated with PCr/CK) suspended in UPW became over 10-fold compared with the control. When 1 {mu}M inositol(1,4,5)trisphosphate (Ins(1,4,5)P{sub 3}) was added in the incubation medium (ICM with PCr/CK), ATP amounts from the filtrate after the second spinning down were further enhanced around three times. This enhancement was almost canceled by Ca{sup 2+}-removal from ICM and by adding thapsigargin, a Ca{sup 2+}-ATPase inhibitor, but not by 2-APB and heparin, Ins(1,4,5)P{sub 3} receptor antagonists. Administration of 500 {mu}M adenosine to the incubation medium (with PCr/CK) failed to enhance the accumulation of ATP in the ER. These findings suggest that the ER originally contains ATP and ATP accumulation in the ER is promoted by PCr/CK and Ins(1,4,5)P{sub 3}.

  15. Diagnostic Accuracy of Post Procedural Creatine Kinase, MB Form can Predict Long-Term Outcomes in Patients Undergoing Selective Percutaneous Coronary Intervention?

    Science.gov (United States)

    Maadani, Mohsen; Parchami-Ghazaee, Sepideh; Barati, Ghodratollah; Soltani, Monireh; Amiri, Elahe; Ghadrdoost, Behshid; Heidarali, Mona

    2014-02-01

    Measuring cardiac markers in blood has been the main strategy for the diagnosis of acute myocardial infarction for nearly 50 years. Creatine kinase-MB (CK-MB) has been demonstrated to be a highly specific marker. The present study aimed to assess the role of CK-MB changes following percutaneous coronary intervention (PCI) to predict one year outcomes of this procedure. This cohort study was conducted on 138 patients diagnosed with coronary artery disease who underwent PCI. Sixty-nine patients who had a CK-MB elevation ≥ 3 times upper limit of normal (ULN) post procedurally were considered as group I and 69 patients without cardiac enzyme rise after PCI were considered as the control group (group II). The composite end point of major adverse cardiac events (MACE) during one year was assessed by telephone follow-up or presentation at clinical visiting, and compared between the two groups. The MACE was defined as the appearance of at least one of the following events: mortality, repeated revascularization procedures, myocardial infarction, or cerebrovascular events. Although one year mortality in the group I was 4 (5.8%), about two times greater than the other group 2 (2.9%), the difference was not significantly discrepant (P = 0.57). Moreover, 8 (11.6%) of patients in group I experienced one year MACE, while this rate in the other group was 4 (5.8%), with insignificant difference (P = 0.22). In group I, one case experienced coronary artery bypass surgery, one, exhibited cerebrovascular disease and one reported ST segment elevation myocardial infarction (STEMI), while two patients in the other group were suspicious of having non-ST segment elevation myocardial infarction (NSTEMI) and candidates for repeated PCI. Multivariate analysis revealed that increased post-procedural CK-MB ≥ 3 times UNL could not predict long-term MACE in patients who underwent selective PCI. Area under the curve (AUC) for predicting one year MACE was 0.593 (95% CI: 0.397 - 0

  16. Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease.

    LENUS (Irish Health Repository)

    Paquet, Claire

    2009-02-01

    The mechanisms of neuronal apoptosis in Creutzfeldt-Jakob disease (CJD) and their relationship to accumulated prion protein (PrP) are unclear. A recent cell culture study showed that intracytoplasmic PrP may induce phosphorylated RNA-dependent protein kinase (PKR(p))-mediated cell stress. The double-stranded RNA protein kinase PKR is a proapoptotic and stress kinase that accumulates in degenerating neurons in Alzheimer disease. To determine whether neuronal apoptosis in human CJD is associated with activation of the PKR(p) signaling pathway, we assessed in situ end labeling and immunocytochemistry for PrP, glial fibrillary acidic protein, CD68, activated caspase 3, and phosphorylated PKR (Thr451) in samples of frontal, occipital, and temporal cortex, striatum, and cerebellum from 6 patients with sporadic CJD and 5 controls. Neuronal immunostaining for activated PKR was found in all CJD cases. The most staining was in nuclei and, in contrast to findings in Alzheimer disease, cytoplasmic labeling was not detected. Both the number and distribution of PKR(p)-positive neurons correlated closely with the extent of neuronal apoptosis, spongiosis, astrocytosis, and microglial activation and with the phenotype and disease severity. There was no correlation with the type, topography, or amount of extracellular PrP deposits. These findings suggest that neuronal apoptosis in human CJD may result from PKR(p)-mediated cell stress and are consistent with recent studies supporting a pathogenic role for intracellular or transmembrane PrP.

  17. Neuronal development in Caenorhabditis elegans is regulated by inhibition of an MLK MAP kinase pathway.

    Science.gov (United States)

    Baker, Scott T; Turgeon, Shane M; Tulgren, Erik D; Wigant, Jeanne; Rahimi, Omeed; Opperman, Karla J; Grill, Brock

    2015-01-01

    We show that loss-of-function mutations in kinases of the MLK-1 pathway (mlk-1, mek-1, and kgb-1/jnk) function cell-autonomously in neurons to suppress defects in synapse formation and axon termination caused by rpm-1 loss of function. Our genetic analysis also suggests that the phosphatase PPM-1, like RPM-1, is a potential inhibitor of kinases in the MLK-1 pathway.

  18. Regulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability

    Science.gov (United States)

    Paul, Jodi R.; Dewoskin, Daniel; McMeekin, Laura J.; Cowell, Rita M.; Forger, Daniel B.; Gamble, Karen L.

    2016-11-01

    How neurons encode intracellular biochemical signalling cascades into electrical signals is not fully understood. Neurons in the central circadian clock in mammals provide a model system to investigate electrical encoding of biochemical timing signals. Here, using experimental and modelling approaches, we show how the activation of glycogen synthase kinase 3 (GSK3) contributes to neuronal excitability through regulation of the persistent sodium current (INaP). INaP exhibits a day/night difference in peak magnitude and is regulated by GSK3. Using mathematical modelling, we predict and confirm that GSK3 activation of INaP affects the action potential afterhyperpolarization, which increases the spontaneous firing rate without affecting the resting membrane potential. Together, these results demonstrate a crucial link between the molecular circadian clock and electrical activity, providing examples of kinase regulation of electrical activity and the propagation of intracellular signals in neuronal networks.

  19. Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris.

    Science.gov (United States)

    Pettijohn, T L; Doyle, T; Spiekerman, A M; Watson, L E; Riggs, M W; Lawrence, M E

    1997-08-15

    Troponin-T was measured in patients with chest pain and negative creatine phosphokinase-MB isoenzymes. Patients with elevated troponin-T had a significantly greater risk of cardiac events over the next 6 months than patients with normal troponin-T.

  20. The contemporary value of peak creatine kinase-MB after ST-segment elevation myocardial infarction above other clinical and angiographic characteristics in predicting infarct size, left ventricular ejection fraction, and mortality.

    Science.gov (United States)

    Hartman, Minke H T; Eppinga, Ruben N; Vlaar, Pieter J J; Lexis, Chris P H; Lipsic, Erik; Haeck, Joost D E; van Veldhuisen, Dirk J; van der Horst, Iwan C C; van der Harst, Pim

    2017-05-01

    Complex multimarker approaches to predict outcome after ST-elevation myocardial infarction (STEMI) have only considered a single baseline sample, while neglecting easily obtainable peak creatine kinase and creatine kinase-MB (CK-MB) values during hospitalization. We studied 476 patients undergoing primary percutaneous coronary intervention for STEMI and cardiac magnetic resonance imaging (CMRI) at 4-6 months after STEMI. We determined the association with cardiac biomarkers (peak CK-MB, peak troponin T, N-terminal pro-brain natriuretic peptide), clinical and angiographic characteristics with infarct size, and LVEF, followed by association with mortality in 1120 STEMI patients. Peak CK-MB was the strongest predictor for infarct size (PMB cutpoints, for differentiation among small (MB measured during hospitalization for STEMI was superior to other clinical and angiographic characteristics in predicting CMRI-defined infarct size and LVEF, and should be included and validated in future multimarker studies. Peak CK-MB cutpoints differentiated among infarct size categories and were associated with increased 90-day mortality risk. © 2016 Wiley Periodicals, Inc.

  1. Protein Kinase Pathways That Regulate Neuronal Survival and Death

    Science.gov (United States)

    2004-08-01

    interneurons of the cerebellum, provide a good model for a maximal concentration of IGF-I (50 ng/ml). The phosphor- VOL. 20, 2000 REGULATION OF NEURONAL...Cell 6:233-244. 272:33271-33278. Lyons GE, Micales BK , Schwarz J, Martin JF, Olson EN (1995) Expres- Ornatsky 01, Cox DM, Tangirala P, Andreucci JJ

  2. The creatine kinase isoenzyme POCT method detection system performance evaluation%肌酸激酶同工酶POCT检测系统的性能评价

    Institute of Scientific and Technical Information of China (English)

    苏荣; 叶桂样; 张劲丰

    2013-01-01

    Objective To Evaluate the precision and accuracy of triage metet fluorescence immunoassay dry quick quantitative detection system in the detection of creatine kinase isoenzyme (CK-MB) to ensure the reliability of bedside testing (POCT) results.Methods The American clinical and Laboratory Standards Institute (CLSI) EP5-A2 file was applied in precision verification,the EP9-A2 file was applied in the method comparison between Triage Metet fluorescence immunoassay dry fast quantitative analyzer and mini VIDAS automated fluorescence immunoassay analyzer,and verify the correctness.Results When the mean CK-MB was 5,39.10 ng/mL,the CV with a group were 3.40,0.79 respectively,CV among groups 3.40,1.07 respectively,which were less than manufacturers' declaration of imprecision;CK-MB results in two instrument were correlated well(r2 =0.998 6,P<0.05),When the medical decision level of CK-MB were 15 and 90,relative standard deviation SE% were 2.53% and 0.17 % respectively,which are less than 1/4 allowable error of CLIA'88(30%).Conclusion The triage metet fluorescence immunoassay dry quick quantitative detection system produced by United States Biosite Biagnostics are with good precision and accuracy in the detection of CK-MB,which meets the clinical needs.%目的 评价Triage Metet荧光免疫干式快速定量检测系统检测肌酸激酶同工酶(CK-MB)的精密度、正确度,以确保床边检验(POCT)结果的可靠性.方法 采用美国临床与实验室标准化协会(CLSI) EP5-A2文件进行精密度验证,采用EP9-A2文件对Triage Metet荧光免疫干式快速定量分析仪与mini VIDAS全自动荧光免疫分析仪进行方法学比对,验证正确度.结果 CK-MB均值为5.00、39.10 ng/mL时CV批内分别为3.40%、0.79%,CV总分别为3.40%、1.07%,均小于厂家声明的不精密度;CK-MB在两仪器的比对结果相关性良好(r2 =0.998 6,P<0.05),CK-MB的医学决定水平分别为15、90,相对偏差(SE%)分别为2.53%、0.17

  3. BDNF stimulation of protein synthesis in cortical neurons requires the MAP kinase-interacting kinase MNK1.

    Science.gov (United States)

    Genheden, Maja; Kenney, Justin W; Johnston, Harvey E; Manousopoulou, Antigoni; Garbis, Spiros D; Proud, Christopher G

    2015-01-21

    Although the MAP kinase-interacting kinases (MNKs) have been known for >15 years, their roles in the regulation of protein synthesis have remained obscure. Here, we explore the involvement of the MNKs in brain-derived neurotrophic factor (BDNF)-stimulated protein synthesis in cortical neurons from mice. Using a combination of pharmacological and genetic approaches, we show that BDNF-induced upregulation of protein synthesis requires MEK/ERK signaling and the downstream kinase, MNK1, which phosphorylates eukaryotic initiation factor (eIF) 4E. Translation initiation is mediated by the interaction of eIF4E with the m(7)GTP cap of mRNA and with eIF4G. The latter interaction is inhibited by the interactions of eIF4E with partner proteins, such as CYFIP1, which acts as a translational repressor. We find that BDNF induces the release of CYFIP1 from eIF4E, and that this depends on MNK1. Finally, using a novel combination of BONCAT and SILAC, we identify a subset of proteins whose synthesis is upregulated by BDNF signaling via MNK1 in neurons. Interestingly, this subset of MNK1-sensitive proteins is enriched for functions involved in neurotransmission and synaptic plasticity. Additionally, we find significant overlap between our subset of proteins whose synthesis is regulated by MNK1 and those encoded by known FMRP-binding mRNAs. Together, our data implicate MNK1 as a key component of BDNF-mediated translational regulation in neurons.

  4. 肌酸激酶测定试剂盒技术审评规范要点概述%Overview of the Evaluation Guidance of the Creatine kinase Assay Kit

    Institute of Scientific and Technical Information of China (English)

    郭丽丽; 赵阳; 孙嵘; 左霖

    2013-01-01

      肌酸激酶是心脑血管慢性损伤的重要指标,目前肌酸激酶测定试剂盒尚无行业标准发布,为了规范肌酸激酶测定试剂盒注册申报和技术审评工作,特制定肌酸激酶测定试剂(盒)产品技术审评规范。本文从适用范围、命名组成、主要技术指标、临床要求和标签、说明书等方面对该规范进行了简要概述,帮助注册申报人更好的把握产品的技术要点,有效的指导注册申报工作。%  Creatine kinase is an important indicator of chronic cardiovascular and cerebrovascular injury, there is no industry standard release at present. The Evaluation Guidance of the Creatine kinase Assay Kit was released by Beijing drug administration in order to standardize the premarket registration and technical review of creatine kinase assay kit, This paper gives a brief introduction to the guidance about the intend use, the name and composition, the main technical indicators, the clinical requirements and label instructions. We hope it wil help the manufacturer grasp of the key points of the product and help the registration application effectively.

  5. Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron-specific dominant negative mitogen activated protein kinase kinase (MEK

    Directory of Open Access Journals (Sweden)

    Kaplan David

    2006-01-01

    Full Text Available Abstract Background Numerous studies have implicated spinal extracellular signal-regulated kinases (ERKs as mediators of nociceptive plasticity. These studies have utilized pharmacological inhibition of MEK to demonstrate a role for ERK signaling in pain, but this approach cannot distinguish between effects of ERK in neuronal and non-neuronal cells. The present studies were undertaken to test the specific role of neuronal ERK in formalin-induced inflammatory pain. Dominant negative MEK (DN MEK mutant mice in which MEK function is suppressed exclusively in neurons were tested in the formalin model of inflammatory pain. Results Formalin-induced second phase spontaneous pain behaviors as well as thermal hyperalgesia measured 1 – 3 hours post-formalin were significantly reduced in the DN MEK mice when compared to their wild type littermate controls. In addition, spinal ERK phosphorylation following formalin injection was significantly reduced in the DN MEK mice. This was not due to a reduction of the number of unmyelinated fibers in the periphery, since these were almost double the number observed in wild type controls. Further examination of the effects of suppression of MEK function on a downstream target of ERK phosphorylation, the A-type potassium channel, showed that the ERK-dependent modulation of the A-type currents is significantly reduced in neurons from DN MEK mice compared to littermate wild type controls. Conclusion Our results demonstrate that the neuronal MEK-ERK pathway is indeed an important intracellular cascade that is associated with formalin-induced inflammatory pain and thermal hyperalgesia.

  6. Creatine uptake in mouse hearts with genetically altered creatine levels

    OpenAIRE

    2008-01-01

    Creatine plays an important role in energy metabolism in the heart. Cardiomyocytes accumulate creatine via a specific creatine transporter (CrT), the capacity of which is reduced in the failing heart, resulting in lower myocardial creatine concentration. Therefore, to gain insight into how the CrT is regulated, we studied two mouse models of severely altered myocardial creatine levels. Cardiac creatine uptake levels were measured in isolated hearts from creatine-free guanidinoacetate-N-methyl...

  7. Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in a novel pathway.

    Science.gov (United States)

    Yang, Rui; Kong, Eryan; Jin, Jing; Hergovich, Alexander; Püschel, Andreas W

    2014-08-15

    The morphology and polarized growth of cells depend on pathways that control the asymmetric distribution of regulatory factors. The evolutionarily conserved Ndr kinases play important roles in cell polarity and morphogenesis in yeast and invertebrates but it is unclear whether they perform a similar function in mammalian cells. Here, we analyze the function of mammalian Ndr1 and Ndr2 (also known as STK38 or STK38L, respectively) in the establishment of polarity in neurons. We show that they act downstream of the tumor suppressor Rassf5 and upstream of the polarity protein Par3 (also known as PARD3). Rassf5 and Ndr1 or Ndr2 are required during the polarization of hippocampal neurons to prevent the formation of supernumerary axons. Mechanistically, the Ndr kinases act by phosphorylating Par3 at Ser383 to inhibit its interaction with dynein, thereby polarizing the distribution of Par3 and reinforcing axon specification. Our results identify a novel Rassf5-Ndr-Par3 signaling cascade that regulates the transport of Par3 during the establishment of neuronal polarity. Their role in neuronal polarity suggests that Ndr kinases perform a conserved function as regulators of cell polarity.

  8. Microglia activation and interaction with neuronal cells in a biochemical model of mevalonate kinase deficiency.

    Science.gov (United States)

    Tricarico, Paola Maura; Piscianz, Elisa; Monasta, Lorenzo; Kleiner, Giulio; Crovella, Sergio; Marcuzzi, Annalisa

    2015-08-01

    Mevalonate kinase deficiency is a rare disease whose worst manifestation, characterised by severe neurologic impairment, is called mevalonic aciduria. The progressive neuronal loss associated to cell death can be studied in vitro with a simplified model based on a biochemical block of the mevalonate pathway and a subsequent inflammatory trigger. The aim of this study was to evaluate the effect of the mevalonate blocking on glial cells (BV-2) and the following effects on neuronal cells (SH-SY5Y) when the two populations were cultured together. To better understand the cross-talk between glial and neuronal cells, as it happens in vivo, BV-2 and SH-SY5Y were co-cultured in different experimental settings (alone, transwell, direct contact); the effect of mevalonate pathway biochemical block by Lovastatin, followed by LPS inflammatory trigger, were evaluated by analysing programmed cell death and mitochondrial membrane potential, cytokines' release and cells' morphology modifications. In this experimental condition, glial cells underwent an evident activation, confirmed by elevated pro-inflammatory cytokines release, typical of these disorders, and a modification in morphology. Moreover, the activation induced an increase in apoptosis. When glial cells were co-cultured with neurons, their activation caused an increase of programmed cell death also in neuronal cells, but only if the two populations were cultured in direct contact. Our findings, being aware of the limitations related to the cell models used, represent a preliminary step towards understanding the pathological and neuroinflammatory mechanisms occurring in mevalonate kinase diseases. Contact co-culture between neuronal and microglial cells seems to be a good model to study mevalonic aciduria in vitro, and to contribute to the identification of potential drugs able to block microglial activation for this orphan disease. In fact, in such a pathological condition, we demonstrated that microglial cells are

  9. 血清肌酸激酶与运动训练控制%Serum Creatine Kinase and Sports Training Control

    Institute of Scientific and Technical Information of China (English)

    陈瑶; 郭子渊

    2014-01-01

    control of glycolysis and mitochondrial. Therefore, in the numerous training monitoring indexes,serum CK has become one of the most important testing indexes which coaches and researchers pay most attention to. The research shows,sports and serum creatine kinase(CK)are closely related,is one of the sensitive indicators for monitoring and evaluation of training load and functional recovery,high strength,high-tempo exercise training or competitions can lead to increase serum CK significantly;With the increase of strength,if not adapting,the special ability movements will decline,if adapting,special abilities will have a breakthrough increase,low CK players,their specific performance is difficult to improve;Serum CK gives a warning effect on the damage of muscle fiber;The use of altitude training,nutrition drugs have influences on CK. In the training of winter sports,track and field,swimming,cycling and other project training,serum CK will be increased at the primary stage,heavy load training stage was positively correlated with serum CK and training load,and the stimulation of exercise intensity is particularly sensitive. In the process of training,coaches and scientific researchers should be timely to monitor the athletes' serum CK,can prevent too large exercise intensity, result injuries,improve the training effect.

  10. Failed cytokinesis of neural progenitors in citron kinase-deficient rats leads to multiciliated neurons.

    Science.gov (United States)

    Anastas, Sara B; Mueller, Dorit; Semple-Rowland, Susan L; Breunig, Joshua J; Sarkisian, Matthew R

    2011-02-01

    Most, if not all, cortical neurons possess a single primary cilium; however, little is known about the mechanisms that control neuronal ciliogenesis. The Citron kinase-deficient (Citron-K(fh/fh)) rat, a model in which failed cytokinesis during development produces cortical neurons containing multiple cellular organelles, provides a unique system in which to examine the relationship between centriole inheritance and neuronal ciliogenesis. In this study, we analyzed the cerebral cortex of these animals using immunohistochemistry, serial confocal, and electron microscopy to determine if the multinucleated neurons present in the cortex of these animals also possess multiple centrioles and cilia. We found that neurons containing multiple nuclei possessed multiple centrioles and cilia whose lengths varied across cortical regions. Despite the presence of multiple cilia, we found that perinatal expression of adenylyl cyclase III, a cilia-specific marker, and somatostatin receptor 3, a receptor enriched in cilia, were preserved in developing Citron-K(fh/fh) brain. Together, these results show that multinucleated neurons arising from defective cytokinesis can extend multiple cilia.

  11. Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase

    Directory of Open Access Journals (Sweden)

    Norelle Christine Wildburger

    2012-07-01

    Full Text Available Glycogen synthase kinase 3 (GSK-3 is an evolutionarily conserved multifaceted ubiquitous enzyme. In the central nervous system (CNS, GSK-3 acts through an intricate network of intracellular signaling pathways culminating in a highly divergent cascade of phosphorylations that control neuronal function during development and adulthood. Accumulated evidence indicates that altered levels of GSK-3 correlate with maladaptive plasticity of neuronal circuitries in psychiatric disorders, addictive behaviors, and neurodegenerative diseases, and pharmacological interventions known to limit GSK-3 can counteract some of these deficits. Thus, targeting the GSK-3 cascade for therapeutic interventions against this broad spectrum of brain diseases has raised a tremendous interest. Yet, the multitude of GSK-3 downstream effectors poses a substantial challenge in the development of selective and potent medications that could efficiently block or modulate the activity of this enzyme. Although the full range of GSK-3 molecular targets are far from resolved, exciting new evidence indicates that ion channels regulating excitability, neurotransmitter release, and synaptic transmission, which ultimately contribute to the mechanisms underling brain plasticity and higher level cognitive and emotional processing, are new promising targets of this enzyme. Here, we will revise this new emerging role of GSK-3 in controlling the activity of voltage-gated Na+, K+, Ca2+ channels and ligand-gated glutamate receptors with the goal of highlighting new relevant endpoints of the neuronal GSK-3 cascade that could provide a platform for a better understanding of the mechanisms underlying the dysfunction of this kinase in the CNS and serve as a guidance for medication development against the broad range of GSK-3-linked human diseases.

  12. Synthesis and biological evaluation of new creatine fatty esters revealed dodecyl creatine ester as a promising drug candidate for the treatment of the creatine transporter deficiency.

    Science.gov (United States)

    Trotier-Faurion, Alexandra; Dézard, Sophie; Taran, Frédéric; Valayannopoulos, Vassili; de Lonlay, Pascale; Mabondzo, Aloïse

    2013-06-27

    The creatine transporter deficiency is a neurological disease caused by impairment of the creatine transporter SLC6A8, resulting in mental retardation associated with a complete absence of creatine within the brain and cellular energy perturbation of neuronal cells. One of the therapeutic hypotheses was to administer lipophilic creatine derivatives which are (1) thought to have better permeability through the cell membrane and (2) would not rely on the activity of SLC6A8 to penetrate the brain. Here, we synthesized creatine fatty esters through original organic chemistry process. A screening on an in vitro rat primary cell-based blood-brain barrier model and on a rat primary neuronal cells model demonstrated interesting properties of these prodrugs to incorporate into endothelial, astroglial, and neuronal cells according to a structure-activity relationship. Dodecyl creatine ester showed then a 20-fold increase in creatine content in pathological human fibroblasts compared with the endogenous creatine content, stating that it could be a promising drug candidate.

  13. Neuronal and intestinal protein kinase d isoforms mediate Na+ (salt taste)-induced learning.

    Science.gov (United States)

    Fu, Ya; Ren, Min; Feng, Hui; Chen, Lu; Altun, Zeynep F; Rubin, Charles S

    2009-08-11

    Ubiquitously expressed protein kinase D (PKD) isoforms are poised to disseminate signals carried by diacylglycerol (DAG). However, the in vivo regulation and functions of PKDs are poorly understood. We show that the Caenorhabditis elegans gene, dkf-2, encodes not just DKF-2A, but also a second previously unknown isoform, DKF-2B. Whereas DKF-2A is present mainly in intestine, we show that DKF-2B is found in neurons. Characterization of dkf-2 null mutants and transgenic animals expressing DKF-2B, DKF-2A, or both isoforms revealed that PKDs couple DAG signals to regulation of sodium ion (Na+)-induced learning. EGL-8 (a phospholipase Cbeta4 homolog) and TPA-1 (a protein kinase Cdelta homolog) are upstream regulators of DKF-2 isoforms in vivo. Thus, pathways containing EGL-8-TPA-1-DKF-2 enable learning and behavioral plasticity by receiving, transmitting, and cooperatively integrating environmental signals targeted to both neurons and intestine.

  14. Neuron Membrane Trafficking and Protein Kinases Involved in Autism and ADHD

    Directory of Open Access Journals (Sweden)

    Yasuko Kitagishi

    2015-01-01

    Full Text Available A brain-enriched multi-domain scaffolding protein, neurobeachin has been identified as a candidate gene for autism patients. Mutations in the synaptic adhesion protein cell adhesion molecule 1 (CADM1 are also associated with autism spectrum disorder, a neurodevelopmental disorder of uncertain molecular origin. Potential roles of neurobeachin and CADM1 have been suggested to a function of vesicle transport in endosomal trafficking. It seems that protein kinase B (AKT and cyclic adenosine monophosphate (cAMP-dependent protein kinase A (PKA have key roles in the neuron membrane trafficking involved in the pathogenesis of autism. Attention deficit hyperactivity disorder (ADHD is documented to dopaminergic insufficiencies, which is attributed to synaptic dysfunction of dopamine transporter (DAT. AKT is also essential for the DAT cell-surface redistribution. In the present paper, we summarize and discuss the importance of several protein kinases that regulate the membrane trafficking involved in autism and ADHD, suggesting new targets for therapeutic intervention.

  15. Focal adhesion kinase modulates radial glia-dependent neuronal migration through connexin-26.

    Science.gov (United States)

    Valiente, Manuel; Ciceri, Gabriele; Rico, Beatriz; Marín, Oscar

    2011-08-10

    Focal adhesion kinase (FAK) is an intracellular kinase and scaffold protein that regulates migration in many different cellular contexts but whose function in neuronal migration remains controversial. Here, we have analyzed the function of FAK in two populations of neurons with very distinct migratory behaviors: cortical interneurons, which migrate tangentially and independently of radial glia; and pyramidal cells, which undergo glial-dependent migration. We found that FAK is dispensable for glial-independent migration but is cell-autonomously required for the normal interaction of pyramidal cells with radial glial fibers. Loss of FAK function disrupts the normal morphology of migrating pyramidal cells, delays migration, and increases the tangential dispersion of neurons arising from the same radial unit. FAK mediates this process by regulating the assembly of Connexin-26 contact points in the membrane of migrating pyramidal cells. These results indicate that FAK plays a fundamental role in the dynamic regulation of Gap-mediated adhesions during glial-guided neuronal migration in the mouse.

  16. Muscarinic modulation of sodium current by activation of protein kinase C in rat hippocampal neurons.

    Science.gov (United States)

    Cantrell, A R; Ma, J Y; Scheuer, T; Catterall, W A

    1996-05-01

    Phosphorylation of brain Na+ channels by protein kinase C (PKC) decreases peak Na+ current and slows macroscopic inactivation, but receptor-activated modulation of Na+ currents via the PKC pathway has not been demonstrated. We have examined modulation of Na+ channels by activation of muscarinic receptors in acutely-isolated hippocampal neurons using whole-cell voltage-clamp recording. Application of the muscarinic agonist carbachol reduced peak Na+ current and slowed macroscopic inactivation at all potentials, without changing the voltage-dependent properties of the channel. These effects were mediated by PKC, since they were eliminated when the specific PKC inhibitor (PKCI19-36) was included in the pipette solution and mimicked by the extracellular application of the PKC activator, OAG. Thus, activation of endogenous muscarinic receptors on hippocampal neurons strongly modulates Na+ channel activity by activation of PKC. Cholinergic input from basal forebrain neurons may have this effect in the hippocampus in vivo.

  17. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Ditlevsen, Dorte K; Køhler, Lene B; Pedersen, Martin Volmer;

    2003-01-01

    The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein...

  18. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Ditlevsen, Dorte K; Køhler, Lene B; Pedersen, Martin V

    2003-01-01

    The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein ki...

  19. The effects of glycogen synthase kinase-3beta in serotonin neurons.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhou

    Full Text Available Glycogen synthase kinase-3 (GSK3 is a constitutively active protein kinase in brain. Increasing evidence has shown that GSK3 acts as a modulator in the serotonin neurotransmission system, including direct interaction with serotonin 1B (5-HT1B receptors in a highly selective manner and prominent modulating effect on 5-HT1B receptor activity. In this study, we utilized the serotonin neuron-selective GSK3β knockout (snGSK3β-KO mice to test if GSK3β in serotonin neurons selectively modulates 5-HT1B autoreceptor activity and function. The snGSK3β-KO mice were generated by crossbreeding GSK3β-floxed mice and ePet1-Cre mice. These mice had normal growth and physiological characteristics, similar numbers of tryptophan hydroxylase-2 (TpH2-expressing serotonin neurons, and the same brain serotonin content as in littermate wild type mice. However, the expression of GSK3β in snGSK3β-KO mice was diminished in TpH2-expressing serotonin neurons. Compared to littermate wild type mice, snGSK3β-KO mice had a reduced response to the 5-HT1B receptor agonist anpirtoline in the regulation of serotonergic neuron firing, cAMP production, and serotonin release, whereas these animals displayed a normal response to the 5-HT1A receptor agonist 8-OH-DPAT. The effect of anpirtoline on the horizontal, center, and vertical activities in the open field test was differentially affected by GSK3β depletion in serotonin neurons, wherein vertical activity, but not horizontal activity, was significantly altered in snGSK3β-KO mice. In addition, there was an enhanced anti-immobility response to anpirtoline in the tail suspension test in snGSK3β-KO mice. Therefore, results of this study demonstrated a serotonin neuron-targeting function of GSK3β by regulating 5-HT1B autoreceptors, which impacts serotonergic neuron firing, serotonin release, and serotonin-regulated behaviors.

  20. Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons

    OpenAIRE

    Thauerer, Bettina; Zur Nedden, Stephanie; Baier-Bitterlich, Gabriele

    2014-01-01

    Serine/threonine protein kinase C-related kinase (PKN/PRK) is a family of three isoenzymes (PKN1, PKN2, PKN3), which are widely distributed in eukaryotic organisms and share the same overall domain structure. The Nterminal region encompasses a conserved repeated domain, termed HR1a-c as well as a HR2/C2 domain. The serine/threonine kinase domain is found in the C-terminal region of the protein and shows high sequence homology to other members of the PKC superfamily. In neurons, PKN1 is the mo...

  1. A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation

    Directory of Open Access Journals (Sweden)

    Shokat Kevan M

    2008-09-01

    Full Text Available Abstract Background Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In Caenorhabditis elegans, the serine/threonine SAD-1 kinase is essential for proper neuronal polarity and synaptic organization. To determine if SAD-1 activity regulates the establishment or maintenance of these neuronal structures, we examined its temporal requirements using a chemical-genetic method that allows for selective and reversible inactivation of its kinase activity in vivo. Results We generated a PP1 analog-sensitive variant of SAD-1. Through temporal inhibition of SAD-1 kinase activity we show that its activity is required for the establishment of both neuronal polarity and synaptic organization. However, while SAD-1 activity is needed strictly when neurons are polarizing, the temporal requirement for SAD-1 is less stringent in synaptic organization, which can also be re-established during maintenance. Conclusion This study reports the first temporal analysis of a neural kinase activity using the chemical-genetic system. It reveals that neuronal polarity and synaptic organization have distinct temporal requirements for SAD-1.

  2. Spindle-F Is the Central Mediator of Ik2 Kinase-Dependent Dendrite Pruning in Drosophila Sensory Neurons.

    Directory of Open Access Journals (Sweden)

    Tzu Lin

    2015-11-01

    Full Text Available During development, certain Drosophila sensory neurons undergo dendrite pruning that selectively eliminates their dendrites but leaves the axons intact. How these neurons regulate pruning activity in the dendrites remains unknown. Here, we identify a coiled-coil protein Spindle-F (Spn-F that is required for dendrite pruning in Drosophila sensory neurons. Spn-F acts downstream of IKK-related kinase Ik2 in the same pathway for dendrite pruning. Spn-F exhibits a punctate pattern in larval neurons, whereas these Spn-F puncta become redistributed in pupal neurons, a step that is essential for dendrite pruning. The redistribution of Spn-F from puncta in pupal neurons requires the phosphorylation of Spn-F by Ik2 kinase to decrease Spn-F self-association, and depends on the function of microtubule motor dynein complex. Spn-F is a key component to link Ik2 kinase to dynein motor complex, and the formation of Ik2/Spn-F/dynein complex is critical for Spn-F redistribution and for dendrite pruning. Our findings reveal a novel regulatory mechanism for dendrite pruning achieved by temporal activation of Ik2 kinase and dynein-mediated redistribution of Ik2/Spn-F complex in neurons.

  3. Enhancement of morphological plasticity in hippocampal neurons by a physically modified saline via phosphatidylinositol-3 kinase.

    Directory of Open Access Journals (Sweden)

    Avik Roy

    Full Text Available Increase of the density of dendritic spines and enhancement of synaptic transmission through ionotropic glutamate receptors are important events, leading to synaptic plasticity and eventually hippocampus-dependent spatial learning and memory formation. Here we have undertaken an innovative approach to upregulate hippocampal plasticity. RNS60 is a 0.9% saline solution containing charge-stabilized nanobubbles that are generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP flow under elevated oxygen pressure. RNS60, but not NS (normal saline, PNS60 (saline containing a comparable level of oxygen without the TCP modification, or RNS10.3 (TCP-modified normal saline without excess oxygen, stimulated morphological plasticity and synaptic transmission via NMDA- and AMPA-sensitive calcium influx in cultured mouse hippocampal neurons. Using mRNA-based targeted gene array, real-time PCR, immunoblot, and immunofluorescence analyses, we further demonstrate that RNS60 stimulated the expression of many plasticity-associated genes in cultured hippocampal neurons. Activation of type IA, but not type IB, phosphatidylinositol-3 (PI-3 kinase by RNS60 together with abrogation of RNS60-mediated upregulation of plasticity-related proteins (NR2A and GluR1 and increase in spine density, neuronal size, and calcium influx by LY294002, a specific inhibitor of PI-3 kinase, suggest that RNS60 upregulates hippocampal plasticity via activation of PI-3 kinase. Finally, in the 5XFAD transgenic model of Alzheimer's disease (AD, RNS60 treatment upregulated expression of plasticity-related proteins PSD95 and NR2A and increased AMPA- and NMDA-dependent hippocampal calcium influx. These results describe a novel property of RNS60 in stimulating hippocampal plasticity, which may help AD and other dementias.

  4. Enhancement of morphological plasticity in hippocampal neurons by a physically modified saline via phosphatidylinositol-3 kinase.

    Science.gov (United States)

    Roy, Avik; Modi, Khushbu K; Khasnavis, Saurabh; Ghosh, Supurna; Watson, Richard; Pahan, Kalipada

    2014-01-01

    Increase of the density of dendritic spines and enhancement of synaptic transmission through ionotropic glutamate receptors are important events, leading to synaptic plasticity and eventually hippocampus-dependent spatial learning and memory formation. Here we have undertaken an innovative approach to upregulate hippocampal plasticity. RNS60 is a 0.9% saline solution containing charge-stabilized nanobubbles that are generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. RNS60, but not NS (normal saline), PNS60 (saline containing a comparable level of oxygen without the TCP modification), or RNS10.3 (TCP-modified normal saline without excess oxygen), stimulated morphological plasticity and synaptic transmission via NMDA- and AMPA-sensitive calcium influx in cultured mouse hippocampal neurons. Using mRNA-based targeted gene array, real-time PCR, immunoblot, and immunofluorescence analyses, we further demonstrate that RNS60 stimulated the expression of many plasticity-associated genes in cultured hippocampal neurons. Activation of type IA, but not type IB, phosphatidylinositol-3 (PI-3) kinase by RNS60 together with abrogation of RNS60-mediated upregulation of plasticity-related proteins (NR2A and GluR1) and increase in spine density, neuronal size, and calcium influx by LY294002, a specific inhibitor of PI-3 kinase, suggest that RNS60 upregulates hippocampal plasticity via activation of PI-3 kinase. Finally, in the 5XFAD transgenic model of Alzheimer's disease (AD), RNS60 treatment upregulated expression of plasticity-related proteins PSD95 and NR2A and increased AMPA- and NMDA-dependent hippocampal calcium influx. These results describe a novel property of RNS60 in stimulating hippocampal plasticity, which may help AD and other dementias.

  5. The changes and significance of serum creatine kinase in patients with salinomycin intoxication%盐霉素中毒患者血清肌酸激酶及其同工酶的变化及意义

    Institute of Scientific and Technical Information of China (English)

    宋世平; 张锡刚; 王淼; 陈建魁; 于农; 金欣; 杜宇; 杨倩琳

    2011-01-01

    Objective:To study the change patterns of serum creatine kinase and it's isocnzyme in patients with salinomycin intoxication.Methods: The serum biochemical indicators were continuously monitored in 12 patients with salinomycin intoxication.Results: The elevation degree of serum creatine kinase and it's isoenzyme, which mainly showed as CK - MM elevation, were positively correlated with the degrees of intoxication.The time interval between intoxication and the arrival of the peak concentration of CK and CK - MB was about two weeks, but the appearance of CK and CK - MB was absolutely not the same, the heavier the pathogenetic condition was, the shorter time interval needed.The effect of glucocorticoid therapy was significant.Severe intoxication may be combined with myocardial damage.Conclusion: The concentration of CK and it's isoenzyme can reflect the pathogenetic condition and serve as biomarker for the treatment and prognosis judgment.%目的:探讨盐霉素中毒患者血清肌酸激酶及其同工酶的变化规律与临床意义.方法:对12例群体性食源性盐霉素中毒病人血清中的生物化学指标进行连续监测.结果:血清肌酸激酶(CK)及其同工酶升高幅度与中毒程度呈正相关,并以CK-MM升高为主;CK和CK-MB峰值时间约2周左右,但两者并不完全一致,病情愈重峰值时间愈短;糖皮质激素疗效显著;重度中毒可合并心肌损伤.结论:动态观察血清CK及CK-MB水平变化对盐霉素中毒救治具有一定的指导意义,它们不仅可以作为诊断横纹肌溶解症的重要指标,还有助于判断中毒程度和治疗效果.

  6. Effects of selective inhibition of protein kinase C, cyclic AMP-dependent protein kinase, and Ca(2+)-calmodulin-dependent protein kinase on neurite development in cultured rat hippocampal neurons.

    Science.gov (United States)

    Cabell, L; Audesirk, G

    1993-06-01

    A variety of experimental evidence suggests that calmodulin and protein kinases, especially protein kinase C, may participate in regulating neurite development in cultured neurons, particularly neurite initiation. However, the results are somewhat contradictory. Further, the roles of calmodulin and protein kinases on many aspects of neurite development, such as branching or elongation of axons vs dendrites, have not been extensively studied. Cultured embryonic rat hippocampal pyramidal neurons develop readily identifiable axons and dendrites. We used this culture system and the new generation of highly specific protein kinase inhibitors to investigate the roles of protein kinases and calmodulin in neurite development. Neurons were cultured for 2 days in the continuous presence of calphostin C (a specific inhibitor of protein kinase C), KT5720 (inhibitor of cyclic AMP-dependent protein kinase), KN62 (inhibitor of Ca(2+)-calmodulin-dependent protein kinase II), or calmidazolium (inhibitor of calmodulin), each at concentrations from approximately 1 to 10 times the concentration reported in the literature to inhibit each kinase by 50%. The effects of phorbol 12-myristate 13-acetate (an activator of protein kinase C) and 4 alpha-phorbol 12,13-didecanoate (an inactive phorbol ester) were also tested. At concentrations that had no effect on neuronal viability, calphostin C reduced neurite initiation and axon branching without significantly affecting the number of dendrites per neuron, dendrite branching, dendrite length, or axon length. Phorbol 12-myristate 13-acetate increased axon branching and the number of dendrites per cell, compared to the inactive 4 alpha-phorbol 12,13-didecanoate. KT5720 inhibited only axon branching. KN62 reduced axon length, the number of dendrites per neuron, and both axon and dendrite branching. At low concentrations, calmidazolium had no effect on any aspect of neurite development, but at high concentrations, calmidazolium inhibited every

  7. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat.

    Science.gov (United States)

    Kazak, Lawrence; Chouchani, Edward T; Jedrychowski, Mark P; Erickson, Brian K; Shinoda, Kosaku; Cohen, Paul; Vetrivelan, Ramalingam; Lu, Gina Z; Laznik-Bogoslavski, Dina; Hasenfuss, Sebastian C; Kajimura, Shingo; Gygi, Steve P; Spiegelman, Bruce M

    2015-10-22

    Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige-fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial creatine kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole-body energy expenditure after administration of a β3-agonist and reduces beige and brown adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PAPERCLIP.

  8. The prion protein constitutively controls neuronal store-operated Ca2+ entry through Fyn kinase

    Science.gov (United States)

    De Mario, Agnese; Castellani, Angela; Peggion, Caterina; Massimino, Maria Lina; Lim, Dmitry; Hill, Andrew F.; Sorgato, M. Catia; Bertoli, Alessandro

    2015-01-01

    The prion protein (PrPC) is a cell surface glycoprotein mainly expressed in neurons, whose misfolded isoforms generate the prion responsible for incurable neurodegenerative disorders. Whereas PrPC involvement in prion propagation is well established, PrPC physiological function is still enigmatic despite suggestions that it could act in cell signal transduction by modulating phosphorylation cascades and Ca2+ homeostasis. Because PrPC binds neurotoxic protein aggregates with high-affinity, it has also been proposed that PrPC acts as receptor for amyloid-β (Aβ) oligomers associated with Alzheimer’s disease (AD), and that PrPC-Aβ binding mediates AD-related synaptic dysfunctions following activation of the tyrosine kinase Fyn. Here, use of gene-encoded Ca2+ probes targeting different cell domains in primary cerebellar granule neurons (CGN) expressing, or not, PrPC, allowed us to investigate whether PrPC regulates store-operated Ca2+ entry (SOCE) and the implication of Fyn in this control. Our findings show that PrPC attenuates SOCE, and Ca2+ accumulation in the cytosol and mitochondria, by constitutively restraining Fyn activation and tyrosine phosphorylation of STIM1, a key molecular component of SOCE. This data establishes the existence of a PrPC-Fyn-SOCE triad in neurons. We also demonstrate that treating cerebellar granule and cortical neurons with soluble Aβ(1–42) oligomers abrogates the control of PrPC over Fyn and SOCE, suggesting a PrPC-dependent mechanizm for Aβ-induced neuronal Ca2+ dyshomeostasis. PMID:26578881

  9. The prion protein constitutively controls neuronal store-operated Ca2+ entry through Fyn kinase

    Directory of Open Access Journals (Sweden)

    Agnese eDe Mario

    2015-10-01

    Full Text Available The prion protein (PrPC is a cell surface glycoprotein mainly expressed in neurons, whose misfolded isoforms generate the prion responsible for incurable neurodegenerative disorders. Whereas PrPC involvement in prion propagation is well established, PrPC physiological function is still enigmatic despite suggestions that it could act in cell signal transduction by modulating phosphorylation cascades and Ca2+ homeostasis. Because PrPC binds neurotoxic protein aggregates with high-affinity, it has also been proposed that PrPC acts as receptor for amyloid-β (Aβ oligomers associated with Alzheimer’s disease (AD, and that PrPC-Aβ binding mediates AD-related synaptic dysfunctions following activation of the tyrosine kinase Fyn.Here, use of gene-encoded Ca2+ probes targeting different cell domains in primary cerebellar granule neurons expressing, or not, PrPC allowed us to investigate whether PrPC regulates store-operated Ca2+ entry (SOCE and the implication of Fyn in this control. Our findings show that PrPC attenuates SOCE, and Ca2+ accumulation in the cytosol and mitochondria, by constitutively restraining Fyn activation and tyrosine phosphorylation of STIM1, a key molecular component of SOCE. This data establishes the existence of a PrPC-Fyn-SOCE triad in neurons.We also demonstrate that treating cerebellar granule and cortical neurons with soluble Aβ(1-42 oligomers abrogates the control of PrPC over Fyn and SOCE, suggesting a PrPC-dependent mechanism for Aβ-induced neuronal Ca2+ dyshomeostasis.

  10. The value of creatine kinase in the early diagnosis of compartment syndrome%肌酸激酶在骨筋膜室综合征早期诊断中的意义

    Institute of Scientific and Technical Information of China (English)

    刘登胜; 张弩; 等

    2001-01-01

    目的 为早期诊断骨筋膜室综合征,降低其致残率,提供一项简便、易行的生化指标。方法 对27例骨筋膜室综合征患者分别测定血清肌酸激酶及筋膜室压力,其中15例作筋膜室切开减压,取肌肉标本进行组织学检查。结果 肌酸激酶值与肌肉组织病理变化程度一致。结论 肌酸激酶值测定可用于骨筋膜室综合征的早期诊断及评估预后。%Objective To diagnose the compartment syndrome early and decreaseits disability rate.Methods The serum creatine kinase (CK) and the compartment pressures were measured in 27 cases of compartment syndrome. Histological examination of muscle specimens were taken in 15 cases who received fasciotomy.Results The serum CK level was corresponded to the pathological changes.Conclusion CK is useful in the early diagnosis and evaluation of prognosis of compartment syndrome.

  11. Preventive effects of physical exercise on the inhibition of creatine kinase in the cerebral cortex of mice exposed to cigarette smoke. DOI: 10.5007/1980-0037.2011v13n2p106

    Directory of Open Access Journals (Sweden)

    Daiane Bittencourt Fraga

    2011-03-01

    Full Text Available Recent studies have shown the health benefits of physical exercise, increasing the oxidative response of muscle. However, the effects of exercise on the brain are poorly understood and contradictory. The inhibition of creatine kinase (CK activity has been associated with the pathogenesis of a large number of diseases, especially in the brain. The objective of this study was to determine the preventive effects of physical exercise in the hippocampus and cerebral cortex of mice after chronic cigarette smoke exposure. Eight to 10-week-old male mice (C57BL-6 were divided into four groups and submitted to an exercise program (swimming, 5 times a week, for 8 weeks. After this period, the animals were passively exposed to cigarette smoke for 60 consecutive days, 3 times a day (4 Marlboro red cigarettes per session, for a total of 12 cigarettes. CK activity was measured in cerebral cortex and hippocampal homogenates. Enzyme activity was inhibited in the cerebral cortex of animals submitted to the inhalation of cigarette smoke. However, exercise prevented this inhibition. In contrast, CK activity remained unchanged in the hippocampus. This inhibition of CK by inhalation of cigarette smoke might be related to the process of cell death. Physical exercise played a preventive role in the inhibition of CK activity caused by exposure to cigarette smoke.

  12. 运动营养补剂对机体乳酸脱氢酶和肌酸激酶的影响观察%Effect of sports nutrition supplements on lactate dehydrogenase and creatine kinase of aerobics athletes

    Institute of Scientific and Technical Information of China (English)

    王建永

    2015-01-01

    目的:分析健美操运动员在服用运动营养补剂后,机体中乳酸脱氢酶与肌酸激酶的变化情况。方法:以郑州师范学院、郑州大学、郑州大学体育学院的160例健美操运动员作为研究对象,依据随机数字表法分为观察和对照两组。观察组80例,采用服用运动营养补剂后进行训练,对照组80例,进行常规的体能训练。对两组的乳酸脱氢酶和肌酸激酶的影响进行分析比较。结果:对照组优秀12例,良好29例,一般39例,优良率为51.3%,明显低于观察组的优为97.5%;差异具有显著性(P<0.05);在乳酸脱氢酶和肌酸激酶浓度比较中,观察组明显优于对照组,具有差异性(P<0.05)。补给后观察组血清HL水平相比C组均有明显升高(P<0.05),HE组与H组相比明显降低(P<0.05);观察组LPL、ApoCⅡ相比于对照组明显降低(P<0.05),说明运动补给可以使血清LPL、ApoCⅡ显著增高,HL明显下降,从而达到调价脂代谢的目的。结论健美操运动员在运用运动营养补剂后,能够通过对乳酸脱氢酶和肌酸激酶浓度降低,从而调节运动员的精神状态,增加爆发力与柔韧度,使体能得以快速恢复。%Objective:To analyze the changes of lactate dehydrogenase and creatine kinase in aerobics athletes after taking sports nutrition supplements.Methods:160 cases of aerobics athletes from Zhengzhou Normal University, Zhengzhou University and Zhengzhou Sport University were selected as research object and randomly divided into Observation Group (n=80)and Control Group (n=80).The Observation Group had physical training after taking the nutrition supplements while the Control Group carried out training without supplement.An analysis and comparison was made on the effects of the supplement on the lactate dehydrogenase and creatine kinase.Results:in the Control Group,the level was excellent in 12

  13. Overexpression of Fyn tyrosine kinase causes abnormal development of primary sensory neurons in Xenopus laevis embryos.

    Science.gov (United States)

    Saito, R; Fujita, N; Nagata, S

    2001-06-01

    The expression and function of the Src family protein tyrosine kinase Fyn in Xenopus laevis embryos have been examined. In situ hybridization analysis demonstrated nervous system-specific expression of Fyn mRNA in tail-bud embryos. However, a class of primary sensory neurons; that is, Rohon-Beard (RB) neurons, which is positive for immunoglobulin superfamily cell adhesion molecules (CAM), neural cell adhesion molecule (N-CAM) and contactin, is devoid of Fyn expression. Injection of Fyn mRNA into one of the blastomeres at the 2-cell stage led to overexpression of Fyn in the injected half of the tail-bud embryos. Immunolabeling of the embryos with anti-HNK-1 antibody revealed that the peripheral axons of RB neurons were partially misguided and bound to each other to form abnormal subcutaneous fascicles. Similar abnormality was induced by injection of the Fyn overexpression vector. The incidence of abnormality appeared dose-dependent, being 68-92% of the injected embryos at 50-400 pg of mRNA. Co-injection of the contactin antisense vector depleted contactin mRNA accumulation without affecting Fyn overexpression and reduced the incidence of the abnormal RB-cell phenotype. However, the N-CAM antisense was ineffective in reducing this abnormality. These results suggest that Fyn can modify signals regulating axonal guidance or fasciculation in the developing X. laevis nervous system and that contactin may affect this action of Fyn.

  14. Investigation of Neuronal Cell Type-Specific Gene Expression of Ca2+/Calmodulin-dependent Protein Kinase II.

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    Mima Kazuko

    2002-01-01

    Full Text Available The promoter activity of the rat Ca2+/calmodulin-dependent protein kinase II gene was analyzed using the luciferase reporter gene in neuronal and non-neuronal cell lines. Neuronal cell type-specific promoter activity was found in the 5'-flanking region of &agr; and &bgr; isoform genes of the kinase. Silencer elements were also found further upstream of promoter regions. A brain-specific protein bound to the DNA sequence of the 5'-flanking region of the gene was found by gel mobility shift analysis in the nuclear extract of the rat brain, including the cerebellum, forebrain, and brainstem, but not in that of non-neuronal tissues, including liver, kidney and spleen. The luciferase expression system and gel shift analysis can be used as an additional and better index by which to monitor gene expression in most cell types.

  15. PRENTAL DIAGNOSIS OF CREATINE KINASE DETECTION IN PERNICIOUS PLACENTA PREVIA%凶险型前置胎盘孕妇肌酸激酶检测的产前诊断价值

    Institute of Scientific and Technical Information of China (English)

    周晓

    2014-01-01

    目的:通过比较孕晚期凶险型前置胎盘孕妇和正常妊娠孕妇血清中肌酸激酶的差异,探讨其用于凶险型前置胎盘合并胎盘植入产前诊断的价值。方法回顾性分析2012年6月至2013年6月江西省妇幼保健院凶险型前置胎盘单胎孕妇92例,其中合并胎盘植入者38例,归入凶险型前置胎盘合并胎盘植入组,其余54例归入未合并胎盘植入组,再随机抽取同期分娩的既往有剖宫产史,本次为正常妊娠的孕妇50例作为对照组,比较三组孕妇血清肌酸激酶水平的差异。结果凶险型前置胎盘合并胎盘植入组CK数值为(128.6±19.8)U/L,未合并胎盘植入组为(67.7±21.2) U/L,单纯剖宫产史组为(65.1±20.3) U/L。凶险型前置胎盘合并胎盘植入时,孕妇血清肌酸激酶水平明显升高,差异具有统计学意义。而在中央型前置胎盘、部分型前置胎盘和边缘型前置胎盘中,肌酸激酶分别为(80.3±38.2) U/L、(77.1±36.0) U/L、(79.6±29.7) U/L,三者差异无统计学意义。结论孕妇血清肌酸激酶的测定对凶险型前置胎盘合并胎盘植入的产前预测有价值,与前置胎盘的类型无关。%Objective:Through comparing the content difference of serum creatine kinasebetween pregnant women with pernicious placenta priva and the normal ones to investigate its value in prenatal diagnosing pernicious placenta priva with placenta accreta.Methods:A total of 92 patients of pernicious placenta priva were retrospectively analyzed in Maternal and Child Care Service Centre of Jiangxi Province from June 2012 to June 2013, among them, 38 cases of pernicious placenta priva with placenta accrete after operation were classified into the study group with placenta accreta, others into the study group without placenta accrete, then 50 women having caesarean section ever but normal pregnance this time into the control group. The levels of serum creatine kinase among three groups were

  16. Silibinin activates AMP-activated protein kinase to protect neuronal cells from oxygen and glucose deprivation-re-oxygenation.

    Science.gov (United States)

    Xie, Zhi; Ding, Sheng-quan; Shen, Ya-fang

    2014-11-14

    In this study, we explored the cytoprotective potential of silibinin against oxygen-glucose deprivation (OGD)-induced neuronal cell damages, and studied underling mechanisms. In vitro model of ischemic stroke was created by keeping neuronal cells (SH-SY5Y cells and primary mouse cortical neurons) in an OGD condition followed by re-oxygenation. Pre-treatment of silibinin significantly inhibited OGD/re-oxygenation-induced necrosis and apoptosis of neuronal cells. OGD/re-oxygenation-induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) reduction were also inhibited by silibinin. At the molecular level, silibinin treatment in SH-SY5Y cells and primary cortical neurons led to significant AMP-activated protein kinase (AMPK) signaling activation, detected by phosphorylations of AMPKα1, its upstream kinase liver kinase B1 (LKB1) and the downstream target acetyl-CoA Carboxylase (ACC). Pharmacological inhibition or genetic depletion of AMPK alleviated the neuroprotective ability of silibinin against OGD/re-oxygenation. Further, ROS scavenging ability by silibinin was abolished with AMPK inhibition or silencing. While A-769662, the AMPK activator, mimicked silibinin actions and suppressed ROS production and neuronal cell death following OGD/re-oxygenation. Together, these results show that silibinin-mediated neuroprotection requires activation of AMPK signaling.

  17. Signal transduction in neurons: effects of cellular prion protein on fyn kinase and ERK1/2 kinase

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    Tomasi Vittorio

    2010-12-01

    Full Text Available Abstract Background It has been reported that cellular prion protein (PrPc co-localizes with caveolin-1 and participates to signal transduction events by recruiting Fyn kinase. As PrPc is a secreted protein anchored to the outer surface membrane through a glycosylphosphatidylinositol (GPI anchor (secPrP and caveolin-1 is located in the inner leaflet of plasma membrane, there is a problem of how the two proteins can physically interact each other and transduce signals. Results By using the GST-fusion proteins system we observed that PrPc strongly interacts with caveolin-1 scaffolding domain and with a caveolin-1 hydrophilic C-terminal region, but not with the caveolin-1 N-terminal region. In vitro binding experiments were also performed to define the site(s of PrPc interacting with cav-1. The results are consistent with a participation of PrPc octapeptide repeats motif in the binding to caveolin-1 scaffolding domain. The caveolar localization of PrPc was ascertained by co-immunoprecipitation, by co-localization after flotation in density gradients and by confocal microscopy analysis of PrPc and caveolin-1 distributions in a neuronal cell line (GN11 expressing caveolin-1 at high levels. Conclusions We observed that, after antibody-mediated cross-linking or copper treatment, PrPc was internalized probably into caveolae. We propose that following translocation from rafts to caveolae or caveolae-like domains, secPrP could interact with caveolin-1 and induce signal transduction events.

  18. Signal transduction in neurons: effects of cellular prion protein on fyn kinase and ERK1/2 kinase.

    Science.gov (United States)

    Tomasi, Vittorio

    2010-12-16

    It has been reported that cellular prion protein (PrPc) co-localizes with caveolin-1 and participates to signal transduction events by recruiting Fyn kinase. As PrPc is a secreted protein anchored to the outer surface membrane through a glycosylphosphatidylinositol (GPI) anchor (secPrP) and caveolin-1 is located in the inner leaflet of plasma membrane, there is a problem of how the two proteins can physically interact each other and transduce signals. By using the GST-fusion proteins system we observed that PrPc strongly interacts with caveolin-1 scaffolding domain and with a caveolin-1 hydrophilic C-terminal region, but not with the caveolin-1 N-terminal region. In vitro binding experiments were also performed to define the site(s) of PrPc interacting with cav-1. The results are consistent with a participation of PrPc octapeptide repeats motif in the binding to caveolin-1 scaffolding domain. The caveolar localization of PrPc was ascertained by co-immunoprecipitation, by co-localization after flotation in density gradients and by confocal microscopy analysis of PrPc and caveolin-1 distributions in a neuronal cell line (GN11) expressing caveolin-1 at high levels. We observed that, after antibody-mediated cross-linking or copper treatment, PrPc was internalized probably into caveolae. We propose that following translocation from rafts to caveolae or caveolae-like domains, secPrP could interact with caveolin-1 and induce signal transduction events.

  19. Value Analysis of Serum Troponin I and Creatine Kinase II Determinated in Patients with Renal Failure%肾衰患者中测定血清肌钙蛋白I和肌酸激酶同工酶II的价值分析

    Institute of Scientific and Technical Information of China (English)

    秦辉

    2014-01-01

    Objective:To investigate the renal failure patients serum troponin I and creatine kinase isoenzymeⅡexpression and clinical diagnosis value.Methods:The ELISA method and enzyme dynamics method were determined in our hospital from 2009 April to 2010 April included 68 cases of renal failure patients between ( observation group) and 68 healthy subjects ( control group) of serum cardiac troponin I and creatine kinase isoenzymeⅡexpression.Results:In the observation group, the patients of cardiac troponin I and creatine kinase isoenzymeⅡwere significantly higher than those in the control group of cardiac troponin I and creatine kinase isoenzymeⅡcontent, the difference was significant (P<0.05);and the severity of renal failure in serum cardiac troponin I and creatine kinase isoenzymeⅡwere significantly higher than that of severity in the light of serum cardiac troponin I and creatine kinase isoenzymeⅡcontent, two groups of data comparison, the difference was significant (P<0.05), statistically meaningful.Conclusion:Renal failure patients serum cardiac troponin I and creatine kinase isoenzymeⅡhave abnormal expression, but as the disease severity in the serum content is also rising, can be used as an important index in diagnosis of renal failure patients.%目的:探讨肾衰患者血清中肌钙蛋白I与肌酸激酶同工酶Ⅱ的表达情况以及临床诊断价值。方法:采取ELISA法和酶动力法分别进行测定我院2009年4月到2010年4月之间收录的68例肾衰患者(观察组)与同期68名健康的对象(对照组)的血清中心肌肌钙蛋白I与肌酸激酶同工酶Ⅱ的表达情况。结果:观察组的患者肌钙蛋白Ⅰ与肌酸激酶同工酶Ⅱ的含量均明显的高于对照组的肌钙蛋白Ⅰ与肌酸激酶同工酶Ⅱ的含量,差异具有显著性(P<0.05);而且肾衰病情严重的血清中的肌钙蛋白Ⅰ与肌酸激酶同工酶Ⅱ的含量明显的高于病情程度轻血清中的肌钙蛋白Ⅰ与肌酸激

  20. Neuronal nitric oxide contributes to neuroplasticity-associated protein expression through cGMP, protein kinase G, and extracellular signal-regulated kinase.

    Science.gov (United States)

    Gallo, Eduardo F; Iadecola, Costantino

    2011-05-11

    Nitric oxide (NO) synthesized by neuronal NO synthase (nNOS) has long been implicated in brain plasticity. However, it is unclear how this short-lived mediator contributes to the long-term molecular changes underlying neuroplasticity, which typically require activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) signaling pathway and gene expression. To address this issue, we used a neuroplasticity model based on treatment of neuronal cultures with bicuculline and a model of experience-dependent plasticity in the barrel cortex. In neuronal cultures, NOS inhibition attenuated the bicuculline-induced activation of ERK and the expression of c-Fos, Egr-1, Arc, and brain-derived neurotrophic factor (BDNF), proteins essential for neuroplasticity. Furthermore, inhibition of the NO target soluble guanylyl cyclase or of the cGMP effector kinase protein kinase G (PKG) reduced both ERK activation and plasticity-related protein expression. NOS inhibition did not affect phosphorylation of cAMP response element-binding protein (CREB), a well-established ERK nuclear target, but it attenuated the nuclear accumulation of the CREB coactivator TORC1 and suppressed the activation of Elk-1, another transcription factor target of ERK. Consistent with these in vitro observations, induction of c-Fos, Egr-1, and BDNF was attenuated in the D1 cortical barrel of nNOS(-/-) mice subjected to single whisker experience. These results establish nNOS-derived NO as a key factor in the expression of proteins involved in neuroplasticity, an effect mediated through cGMP, PKG, and ERK signaling. These actions of NO do not depend on CREB phosphorylation but may involve TORC1 and Elk-1. Our data unveil a previously unrecognized link between neuronal NO and the molecular machinery responsible for the sustained synaptic changes underlying neuroplasticity.

  1. Utility of peak creatine kinase-MB measurements in predicting myocardial infarct size, left ventricular dysfunction, and outcome after first anterior wall acute myocardial infarction (from the INFUSE-AMI trial).

    Science.gov (United States)

    Dohi, Tomotaka; Maehara, Akiko; Brener, Sorin J; Généreux, Philippe; Gershlick, Anthony H; Mehran, Roxana; Gibson, C Michael; Mintz, Gary S; Stone, Gregg W

    2015-03-01

    Infarct size after ST-segment elevation myocardial infarction (STEMI) is associated with long-term clinical outcomes. However, there is insufficient information correlating creatine kinase-MB (CK-MB) or troponin levels to infarct size and infarct location in first-time occurrence of STEMI. We, therefore, assessed the utility of CK-MB measurements after primary percutaneous coronary intervention of a first anterior STEMI using bivalirudin anticoagulation in patients who were randomized to intralesion abciximab versus no abciximab and to manual thrombus aspiration versus no aspiration. Infarct size (as a percentage of total left ventricular [LV] mass) and LV ejection fraction (LVEF) were evaluated by cardiac magnetic resonance imaging at 30 days and correlated to peak CK-MB. Peak CK-MB (median 240 IU/L; interquartile range 126 to 414) was significantly associated with infarct size and with LVEF (r = 0.67, p MB tertile group than in the other tertiles (87.6% vs 49.5% vs 9.1%, p MB of at least 300 IU/L predicted with moderate accuracy both a large infarct size (area under the curve 0.88) and an LVEF ≤40% (area under the curve 0.78). Furthermore, CK-MB was an independent predictor of 1-year major adverse cardiac events (hazard ratio 1.42 per each additional 100 IU/L [1.20 to 1.67], p MB measurement is useful in estimating infarct size and LVEF and in predicting 1-year clinical outcomes after primary percutaneous coronary intervention for first anterior STEMI. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Protein kinase D interacts with neuronal nitric oxide synthase and phosphorylates the activatory residue serine 1412.

    Directory of Open Access Journals (Sweden)

    Lucía Sánchez-Ruiloba

    Full Text Available Neuronal Nitric Oxide Synthase (nNOS is the biosynthetic enzyme responsible for nitric oxide (·NO production in muscles and in the nervous system. This constitutive enzyme, unlike its endothelial and inducible counterparts, presents an N-terminal PDZ domain known to display a preference for PDZ-binding motifs bearing acidic residues at -2 position. In a previous work, we discovered that the C-terminal end of two members of protein kinase D family (PKD1 and PKD2 constitutes a PDZ-ligand. PKD1 has been shown to regulate multiple cellular processes and, when activated, becomes autophosphorylated at Ser 916, a residue located at -2 position of its PDZ-binding motif. Since nNOS and PKD are spatially enriched in postsynaptic densities and dendrites, the main objective of our study was to determine whether PKD1 activation could result in a direct interaction with nNOS through their respective PDZ-ligand and PDZ domain, and to analyze the functional consequences of this interaction. Herein we demonstrate that PKD1 associates with nNOS in neurons and in transfected cells, and that kinase activation enhances PKD1-nNOS co-immunoprecipitation and subcellular colocalization. However, transfection of mammalian cells with PKD1 mutants and yeast two hybrid assays showed that the association of these two enzymes does not depend on PKD1 PDZ-ligand but its pleckstrin homology domain. Furthermore, this domain was able to pull-down nNOS from brain extracts and bind to purified nNOS, indicating that it mediates a direct PKD1-nNOS interaction. In addition, using mass spectrometry we demonstrate that PKD1 specifically phosphorylates nNOS in the activatory residue Ser 1412, and that this phosphorylation increases nNOS activity and ·NO production in living cells. In conclusion, these novel findings reveal a crucial role of PKD1 in the regulation of nNOS activation and synthesis of ·NO, a mediator involved in physiological neuronal signaling or neurotoxicity under

  3. Protein Kinase D Interacts with Neuronal Nitric Oxide Synthase and Phosphorylates the Activatory Residue Serine1412

    Science.gov (United States)

    García-Guerra, Lucía; Pose-Utrilla, Julia; Rodríguez-Crespo, Ignacio; Iglesias, Teresa

    2014-01-01

    Neuronal Nitric Oxide Synthase (nNOS) is the biosynthetic enzyme responsible for nitric oxide (·NO) production in muscles and in the nervous system. This constitutive enzyme, unlike its endothelial and inducible counterparts, presents an N-terminal PDZ domain known to display a preference for PDZ-binding motifs bearing acidic residues at -2 position. In a previous work, we discovered that the C-terminal end of two members of protein kinase D family (PKD1 and PKD2) constitutes a PDZ-ligand. PKD1 has been shown to regulate multiple cellular processes and, when activated, becomes autophosphorylated at Ser916, a residue located at -2 position of its PDZ-binding motif. Since nNOS and PKD are spatially enriched in postsynaptic densities and dendrites, the main objective of our study was to determine whether PKD1 activation could result in a direct interaction with nNOS through their respective PDZ-ligand and PDZ domain, and to analyze the functional consequences of this interaction. Herein we demonstrate that PKD1 associates with nNOS in neurons and in transfected cells, and that kinase activation enhances PKD1-nNOS co-immunoprecipitation and subcellular colocalization. However, transfection of mammalian cells with PKD1 mutants and yeast two hybrid assays showed that the association of these two enzymes does not depend on PKD1 PDZ-ligand but its pleckstrin homology domain. Furthermore, this domain was able to pull-down nNOS from brain extracts and bind to purified nNOS, indicating that it mediates a direct PKD1-nNOS interaction. In addition, using mass spectrometry we demonstrate that PKD1 specifically phosphorylates nNOS in the activatory residue Ser1412, and that this phosphorylation increases nNOS activity and ·NO production in living cells. In conclusion, these novel findings reveal a crucial role of PKD1 in the regulation of nNOS activation and synthesis of ·NO, a mediator involved in physiological neuronal signaling or neurotoxicity under pathological conditions

  4. Oral creatine supplementation augments the repeated bout effect.

    Science.gov (United States)

    Veggi K, F T; Machado, Marco; Koch, Alexander J; Santana, Sandro C; Oliveira, Sedison S; Stec, Michael J

    2013-08-01

    We examined the effects of creatine supplementation on the response to repeated bouts of resistance exercise. Young men (24.1 ± 5.2 yr) were divided into Creatine (CM, n = 9) and Placebo (PL, n = 9) groups. On day (D) 1 and D15, subjects performed four sets of bicep curls at 75% 1-RM to concentric failure. On D8-D13, subjects consumed either 20g/d creatine monohydrate or placebo. Muscle soreness and elbow joint range of motion (ROM) were assessed on D1-D5 and D15-D19. Serum creatine kinase activity (CK) was assessed on D1, D3, D5, D15, D17, and D19. The first exercise bout produced increases in muscle soreness and CK, and decreases in ROM in both groups (p Creatine supplementation provides an additive effect on blunting the rise of muscle damage markers following a repeated bout of resistance exercise. The mechanism by which creatine augments the repeated bout effect is unknown but is likely due to a combination of creatine's multifaceted functions.

  5. Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons.

    Science.gov (United States)

    Thauerer, Bettina; Zur Nedden, Stephanie; Baier-Bitterlich, Gabriele

    2014-05-01

    Serine/threonine protein kinase C-related kinase (PKN/PRK) is a family of three isoenzymes (PKN1, PKN2, PKN3), which are widely distributed in eukaryotic organisms and share the same overall domain structure. The Nterminal region encompasses a conserved repeated domain, termed HR1a-c as well as a HR2/C2 domain. The serine/threonine kinase domain is found in the C-terminal region of the protein and shows high sequence homology to other members of the PKC superfamily. In neurons, PKN1 is the most abundant isoform and has been implicated in a variety of functions including cytoskeletal organization and neuronal differentiation and its deregulation may contribute to neuropathological processes such as amyotrophic lateral sclerosis and Alzheimer's disease. We have recently identified a candidate role of PKN1 in the regulation of neuroprotective processes during hypoxic stress. Our key findings were that: 1) the activity of PKN1 was significantly increased by hypoxia (1% O2) and neurotrophins (nerve growth factor and purine nucleosides); 2) Neuronal cells, deficient of PKN1 showed a decrease of cell viability and neurite formation along with a disturbance of the F-actinassociated cytoskeleton; 3) Purine nucleoside-mediated neuroprotection during hypoxia was severely hampered in PKN1 deficient neuronal cells, altogether suggesting a potentially critical role of PKN1 in neuroprotective processes. This review gives an up-to-date overview of the PKN family with a special focus on the neuroprotective role of PKN1 in hypoxia.

  6. Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons

    Science.gov (United States)

    Thauerer, Bettina; zur Nedden, Stephanie; Baier-Bitterlich, Gabriele

    2014-01-01

    Serine/threonine protein kinase C-related kinase (PKN/PRK) is a family of three isoenzymes (PKN1, PKN2, PKN3), which are widely distributed in eukaryotic organisms and share the same overall domain structure. The Nterminal region encompasses a conserved repeated domain, termed HR1a-c as well as a HR2/C2 domain. The serine/threonine kinase domain is found in the C-terminal region of the protein and shows high sequence homology to other members of the PKC superfamily. In neurons, PKN1 is the most abundant isoform and has been implicated in a variety of functions including cytoskeletal organization and neuronal differentiation and its deregulation may contribute to neuropathological processes such as amyotrophic lateral sclerosis and Alzheimer’s disease. We have recently identified a candidate role of PKN1 in the regulation of neuroprotective processes during hypoxic stress. Our key findings were that: 1) the activity of PKN1 was significantly increased by hypoxia (1% O2) and neurotrophins (nerve growth factor and purine nucleosides); 2) Neuronal cells, deficient of PKN1 showed a decrease of cell viability and neurite formation along with a disturbance of the F-actinassociated cytoskeleton; 3) Purine nucleoside-mediated neuroprotection during hypoxia was severely hampered in PKN1 deficient neuronal cells, altogether suggesting a potentially critical role of PKN1 in neuroprotective processes. This review gives an up-to-date overview of the PKN family with a special focus on the neuroprotective role of PKN1 in hypoxia. PMID:24851086

  7. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies.

    Science.gov (United States)

    Skibinski, Gaia; Nakamura, Ken; Cookson, Mark R; Finkbeiner, Steven

    2014-01-08

    By combining experimental neuron models and mathematical tools, we developed a "systems" approach to deconvolve cellular mechanisms of neurodegeneration underlying the most common known cause of Parkinson's disease (PD), mutations in leucine-rich repeat kinase 2 (LRRK2). Neurons ectopically expressing mutant LRRK2 formed inclusion bodies (IBs), retracted neurites, accumulated synuclein, and died prematurely, recapitulating key features of PD. Degeneration was predicted from the levels of diffuse mutant LRRK2 that each neuron contained, but IB formation was neither necessary nor sufficient for death. Genetic or pharmacological blockade of its kinase activity destabilized LRRK2 and lowered its levels enough to account for the moderate reduction in LRRK2 toxicity that ensued. By contrast, targeting synuclein, including neurons made from PD patient-derived induced pluripotent cells, dramatically reduced LRRK2-dependent neurodegeneration and LRRK2 levels. These findings suggest that LRRK2 levels are more important than kinase activity per se in predicting toxicity and implicate synuclein as a major mediator of LRRK2-induced neurodegeneration.

  8. Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury

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    Mu Jin

    2015-01-01

    Full Text Available The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK, serine-threonine protein kinase (Akt and c-Jun N-terminal kinase (JNK signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt and phosphorylated ERK (p-ERK increased immediately after reperfusion, peaked at 4 hours (p-Akt or 2 hours (p-ERK, decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.

  9. Mutant LRRK2 Toxicity in Neurons Depends on LRRK2 Levels and Synuclein But Not Kinase Activity or Inclusion Bodies

    Science.gov (United States)

    Skibinski, Gaia; Nakamura, Ken; Cookson, Mark R.

    2014-01-01

    By combining experimental neuron models and mathematical tools, we developed a “systems” approach to deconvolve cellular mechanisms of neurodegeneration underlying the most common known cause of Parkinson's disease (PD), mutations in leucine-rich repeat kinase 2 (LRRK2). Neurons ectopically expressing mutant LRRK2 formed inclusion bodies (IBs), retracted neurites, accumulated synuclein, and died prematurely, recapitulating key features of PD. Degeneration was predicted from the levels of diffuse mutant LRRK2 that each neuron contained, but IB formation was neither necessary nor sufficient for death. Genetic or pharmacological blockade of its kinase activity destabilized LRRK2 and lowered its levels enough to account for the moderate reduction in LRRK2 toxicity that ensued. By contrast, targeting synuclein, including neurons made from PD patient-derived induced pluripotent cells, dramatically reduced LRRK2-dependent neurodegeneration and LRRK2 levels. These findings suggest that LRRK2 levels are more important than kinase activity per se in predicting toxicity and implicate synuclein as a major mediator of LRRK2-induced neurodegeneration. PMID:24403142

  10. Dioxin modulates expression of receptor for activated C kinase (RACK-1) in developing neurons

    Energy Technology Data Exchange (ETDEWEB)

    Yang, J.H.; Kim, S.Y.; Lee, H.G.; Kim, M.Y.; Lee, J.H.; Chae, W.G. [Catholic Univ. of Daegu, Dept. of Pharmacology/Toxicology, Daegu (Korea)

    2004-09-15

    TCDD is sensitive to the central nerve system of the developing brain. The TCDD-induced neurodevelopmental deficits include the cognitive disability and motor dysfunction. While TCDD may lead to neurodevelopmental and neurobehavioral deficit, it is not known which molecular substances are intracellular targets for TCDD. Since TCDD accumulates in brain and the brain contains the Ah receptor, it is possible that TCDD may act at the target site such as cerebellum, which is responsible for cognitive abilities and motor function. A recent in vitro studies using cerebellar granule cells demonstrated a translocation of PKC-{alpha} and {epsilon} following the TCDD or PCB exposure. One of the most pivotal second messenger molecules involved in neuronal function and development is protein kinase C (PKC). PKC signaling pathways have been implicated as an important factor in learning and memory processes. PKC signaling events are optimized by the adaptor proteins, which organize PKCs near their selective substrates and away from others. RACK-1(receptor for activated C-kinase) is one of adaptor proteins that anchor the activated PKC at the site of translocation 6. RACKs bind PKC only in the presence of PKC activators. RACKs are 30- and 36-kDa proteins located in cytoskeletal compartment and play a key role in PKC activation and in membrane amchoring. Since different PKC isoforms translocate to distinct subcellular sites on activation, it is suggested that isoform-specific RACK may be present. Activation of certain PKC isoforms (PKC-a and {beta}II) is preferentially associated with RACK-1. While TCDD modulates PKC signaling pathway, role of RACK-1 on TCDD-mediated signaling pathway is not known. To identify the intracellular target for TCDD and understand a mechanism of signaling pathway in the developing brain, the present study attempted to analyze effects of RACK-1 in the cerebellar granule cells following TCDD exposure.

  11. AMP kinase regulates ligand-gated K-ATP channels in substantia nigra dopamine neurons.

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    Shen, Ke-Zhong; Wu, Yan-Na; Munhall, Adam C; Johnson, Steven W

    2016-08-25

    AMP-activated protein kinase (AMPK) is a master enzyme that regulates ATP-sensitive K(+) (K-ATP) channels in pancreatic beta-cells and cardiac myocytes. We used patch pipettes to record currents and potentials to investigate effects of AMPK on K-ATP currents in substantia nigra compacta (SNC) dopamine neurons in slices of rat midbrain. When slices were superfused repeatedly with the K-ATP channel opener diazoxide, we were surprised to find that diazoxide currents gradually increased in magnitude, reaching 300% of the control value 60min after starting whole-cell recording. However, diazoxide current increased significantly more, to 472% of control, when recorded in the presence of the AMPK activator A769662. Moreover, superfusing the slice with the AMPK blocking agent dorsomorphin significantly reduced diazoxide current to 38% of control. Control experiments showed that outward currents evoked by the K-ATP channel opener NN-414 also increased over time, but not currents evoked by the GABAB agonist baclofen. Delaying the application of diazoxide after starting whole-cell recording correlated with augmentation of current. Loose-patch recording showed that diazoxide produced a 34% slowing of spontaneous firing rate that did not intensify with repeated applications of diazoxide. However, superfusion with A769662 significantly augmented the inhibitory effect of diazoxide on firing rate. We conclude that K-ATP channel function is augmented by AMPK, which is activated during the process of making whole-cell recordings. Our results suggest that AMPK and K-ATP interactions may play an important role in regulating dopamine neuronal excitability.

  12. The clinical significance of serum creatine kinase isoenzyme MB and troponin I for judging the myocardial injury of hand foot mouth disease (HFMD)children%CK-MB 及 cTnI 检测对手足口病患儿心肌损害的临床意义

    Institute of Scientific and Technical Information of China (English)

    汤淑斌; 庞伟斌

    2015-01-01

    目的:探讨血清肌酸激酶同工酶(CK-MB)及肌钙蛋白 I(cTnI)检测对手足口病(HFMD)患儿心肌损害的临床意义。方法选择2012年7月至2013年6月期间在我院住院的80例手足口病患儿为 HFMD 组;50例健康体检儿童为对照组,比较分析两组 CK-MB 及 cTnI 水平。结果手足口病患儿 CK-MB 水平为38.10±19.50 U/L,cT-nI 水平为0.2±0.07μg/L,均高于对照组(14.80±10.30 U/L,0.07±0.02μg/L),差异有统计学意义(P <0.05)。HFMD 组 CK-MB 检测阳性率56.3%(45/80),明显高于 cTnI 的33.8%(27/80),差异有统计学意义(P <0.05)。经积极治疗后 CK-MB 及 cTnI 水平均明显下降,较入院时比较,差异有统计学意义(P <0.05)。结论联合检测血清CK-MB 及 cTnI 对手足口病合并心肌损害的早期诊断具有重要临床意义。%Objective To explore the clinical significance of serum creatine kinase isoenzyme MB and troponin I for judging the myocardial injury of hand foot mouth disease (HFMD)children.Methods Choose 80 HFMD patients who were hospitalized with in our college from July 2012 to June 2014 as the observation group,and selected 50 healthy check-up children as the control group.We detected and comparatively analyzed the children of the two groups in crea-tine kinase isoenzyme and troponin I difference.Results HFMD group of creatine kinase isoenzyme and troponin I tese results are greatly higher than control group,and in HFMD group the creatine kinase isoenzyme and troponin I test re-sults had significantly reduced after taking effective treatment,and in HFMD group the positive rate of creatine kinase isoenzyme was great higher than the positive rate of troponin I,all the differences were statistically significant(P <0.05).Conclusion Combined detection of serum creatine kinase isoenzyme and troponin I have the important clinical meaning for the early clinical

  13. Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients.

    Science.gov (United States)

    Santambrogio, Paolo; Dusi, Sabrina; Guaraldo, Michela; Rotundo, Luisa Ida; Broccoli, Vania; Garavaglia, Barbara; Tiranti, Valeria; Levi, Sonia

    2015-09-01

    Pantothenate kinase-associated neurodegeneration is an early onset autosomal recessive movement disorder caused by mutation of the pantothenate kinase-2 gene, which encodes a mitochondrial enzyme involved in coenzyme A synthesis. The disorder is characterised by high iron levels in the brain, although the pathological mechanism leading to this accumulation is unknown. To address this question, we tested primary skin fibroblasts from three patients and three healthy subjects, as well as neurons induced by direct fibroblast reprogramming, for oxidative status, mitochondrial functionality and iron parameters. The patients' fibroblasts showed altered oxidative status, reduced antioxidant defence, and impaired cytosolic and mitochondrial aconitase activities compared to control cells. Mitochondrial iron homeostasis and functionality analysis of patient fibroblasts indicated increased labile iron pool content and reactive oxygen species development, altered mitochondrial shape, decreased membrane potential and reduced ATP levels. Furthermore, analysis of induced neurons, performed at a single cell level, confirmed some of the results obtained in fibroblasts, indicating an altered oxidative status and signs of mitochondrial dysfunction, possibly due to iron mishandling. Thus, for the first time, altered biological processes have been identified in vitro in live diseased neurons. Moreover, the obtained induced neurons can be considered a suitable human neuronal model for the identification of candidate therapeutic compounds for this disease.

  14. Homozygous mutation of focal adhesion kinase in embryonic stem cell derived neurons: normal electrophysiological and morphological properties in vitro

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    Komiyama NH

    2006-06-01

    Full Text Available Abstract Background Genetically manipulated embryonic stem (ES cell derived neurons (ESNs provide a powerful system with which to study the consequences of gene manipulation in mature, synaptically connected neurons in vitro. Here we report a study of focal adhesion kinase (FAK, which has been implicated in synapse formation and regulation of ion channels, using the ESN system to circumvent the embryonic lethality of homozygous FAK mutant mice. Results Mouse ES cells carrying homozygous null mutations (FAK-/- were generated and differentiated in vitro into neurons. FAK-/- ESNs extended axons and dendrites and formed morphologically and electrophysiologically intact synapses. A detailed study of NMDA receptor gated currents and voltage sensitive calcium currents revealed no difference in their magnitude, or modulation by tyrosine kinases. Conclusion FAK does not have an obligatory role in neuronal differentiation, synapse formation or the expression of NMDA receptor or voltage-gated calcium currents under the conditions used in this study. The use of genetically modified ESNs has great potential for rapidly and effectively examining the consequences of neuronal gene manipulation and is complementary to mouse studies.

  15. The role of dietary creatine.

    Science.gov (United States)

    Brosnan, Margaret E; Brosnan, John T

    2016-08-01

    The daily requirement of a 70-kg male for creatine is about 2 g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body Creatine is a carninutrient, which means that it is only available to adults via animal foodstuffs, principally skeletal muscle, or via supplements. Infants receive creatine in mother's milk or in milk-based formulas. Vegans and infants fed on soy-based formulas receive no dietary creatine. Plasma and muscle creatine levels are usually somewhat lower in vegetarians than in omnivores. Human intake of creatine was probably much higher in Paleolithic times than today; some groups with extreme diets, such as Greenland and Alaskan Inuit, ingest much more than is currently typical. Creatine is synthesized from three amino acids: arginine, glycine and methionine (as S-adenosylmethionine). Humans can synthesize sufficient creatine for normal function unless they have an inborn error in a creatine-synthetic enzyme or a problem with the supply of substrate amino acids. Carnivorous animals, such as lions and wolves, ingest much larger amounts of creatine than humans would. The gastrointestinal tract and the liver are exposed to dietary creatine in higher concentrations before it is assimilated by other tissues. In this regard, our observations that creatine supplementation can prevent hepatic steatosis (Deminice et al. J Nutr 141:1799-1804, 2011) in a rodent model may be a function of the route of dietary assimilation. Creatine supplementation has also been reported to improve the intestinal barrier function of the rodent suffering from inflammatory bowel disease.

  16. SERUM ACTIVITIES OF ASPARTATE AMINOTRANSFERASE, CREATINE KINASE AND LACTATE DEHYDROGENASE IN HORSES WITH COLIC ATIVIDADE SÉRICA DAS ENZIMAS ASPARTATO AMINOTRANSFERASE, CREATINA QUINASE E LACTATO DESIDROGENASE EM EQÜINOS COM CÓLICA

    Directory of Open Access Journals (Sweden)

    Aureo Evangelista Santana

    2008-12-01

    Full Text Available Seventy equines distributed in two experimental groups were used, G1 (20 healthy equines, and G2 (50 equines with colic. Blood samples were obtained by jugular vein puncture in ten different moments. The variables aspartate aminotransferase (AST, creatine kinase (CK, and lactate dehydrogenase (LDH were determined by spectrophotometric assay using specific reagents. The average values presented by the animals of the G2 for variables CK, AST, and LDH were higher (P<0.05 than the values presented by the animals of the G1 in all the evaluation moments. The results showed for G2 animals suggest the existence of acute muscle injury. The muscle injuries in equines with colic were attributed to the tissue hypoperfusion, and the muscular damage.

    KEY WORDS: Acute abdomen, horses, muscles enzyme. De setenta eqüinos, distribuídos em dois grupos experimentais – G1 (vinte eqüinos hígidos e G2 (cinqüenta eqüinos com cólica –, colheram-se amostras de sangue em dez diferentes momentos, mediante punção da jugular, para a determinação da atividade sérica das enzimas aspartato aminotransferase (AST, creatina quinase (CK e lactato desidrogenase (LDH. Os valores médios apresentados pelos animais do G2, para as variáveis CK, AST e LDH, foram superiores (P<0,05 aos valores médios apresentados pelos animais do G1 em todos os momentos de avaliação. Os resultados apresentados pelos animais com cólica (G2 sugerem a existência de lesão muscular aguda, porém com tendência a cura, e foram atribuídos a hipoperfusão tecidual e a traumas musculares. A análise seriada das enzimas CK, AST e LDH auxilia tanto no diagnóstico de lesões musculares em eqüinos com cólica como no acompanhamento da evolução do processo de cura.

    PALAVRAS-CHAVES: Abdômen agudo, cavalos, enzimas musculares.

  17. Short-term prognostic value of perioperative coronary sinus-derived-serum cardiac troponin-I, creatine kinase-MB, lactate, pyruvate, and lactate-pyruvate ratio in adult patients undergoing open heart surgery

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    Ujjwal Kumar Chowdhury

    2016-01-01

    Full Text Available Objectives: To investigate the release pattern of different cardiac metabolites and biomarkers directly from the coronary sinus (CS and to establish the diagnostic discrimination limits of each marker protein and metabolites to evaluate perioperative myocardial injury in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB. Patients and Methods: Sixty-eight patients undergoing first mitral and/or aortic valve replacements with/without coronary artery bypass grafting and Bentall procedure under CPB and blood cardioplegic arrest were studied. All cardiac metabolites and biomarkers were measured in serial CS-derived blood samples at pre-CPB, immediate post aortic declamping, 10 minutes post-CPB and 12 hrs post-CPB. Results: Receiver operating characteristic curve analysis of cardiac biomarkers indicated lactate-pyruvate ratio as the superior diagnostic discriminator of myocardial injury with an optimal "cut-off" value >10.8 immediately after aortic declamping (AUC, 0.92; 95% CI: 0.85-0.98. Lactate was the second best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >2mmol/l at immediately after aortic declamping (AUC, 0.89; 95% CI: 0.80-0.96. Cardiac troponin-I was the third best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >2.1ng/ml at immediately after aortic declamping (AUC, 0.88; 95% CI: 0.80-0.95. Creatine kinase-MB was the fourth best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >58 log units/ml prior to decanulation (AUC, 0.85; 95% CI: 0.78-0.94. Conclusions: Measurable cardiac damage exists in all patients undergoing cardiac surgery under cardioplegic arrest. The degree of myocardial injury is more in patients with poor ventricular function and those requiring longer aortic clamp time. CS-derived lactate-pyruvate ratio, lactate, cTn-I served as superior diagnostic discriminators of peri-operative myocardial damage.

  18. c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons.

    Science.gov (United States)

    Zhou, Qiongqiong; Lam, Philip Y; Han, Derick; Cadenas, Enrique

    2008-01-01

    This study examines the role of c-jun N-terminal kinase (JNK) in mitochondrial signaling and bioenergetics in primary cortical neurons and isolated rat brain mitochondria. Exposure of neurons to either anisomycin (an activator of JNK/p38 mitogen-activated protein kinases) or H2O2 resulted in activation (phosphorylation) of JNK (mostly p46(JNK1)) and its translocation to mitochondria. Experiments with mitochondria isolated from either rat brain or primary cortical neurons and incubated with proteinase K revealed that phosphorylated JNK was associated with the outer mitochondrial membrane; this association resulted in the phosphorylation of the E(1alpha) subunit of pyruvate dehydrogenase, a key enzyme that catalyzes the oxidative decarboxylation of pyruvate and that links two major metabolic pathways: glycolysis and the tricarboxylic acid cycle. JNK-mediated phosphorylation of pyruvate dehydrogenase was not observed in experiments carried out with mitoplasts, thus suggesting the requirement of intact, functional mitochondria for this effect. JNK-mediated phosphorylation of pyruvate dehydrogenase was associated with a decline in its activity and, consequently, a shift to anaerobic pyruvate metabolism: the latter was confirmed by increased accumulation of lactic acid and decreased overall energy production (ATP levels). Pyruvate dehydrogenase appears to be a specific phosphorylation target for JNK, for other kinases, such as protein kinase A and protein kinase C did not elicit pyruvate dehydrogenase phosphorylation and did not decrease the activity of the complex. These results suggest that JNK mediates a signaling pathway that regulates metabolic functions in mitochondria as part of a network that coordinates cytosolic and mitochondrial processes relevant for cell function.

  19. Changes of plasma glutathione S-transferase, D-lactate and creatine kinase levels in Wistar rats with acute intestinal ischemia%Wistar大鼠急性小肠缺血时血浆谷胱甘肽S转移酶、D-乳酸盐及肌酸激酶水平变化

    Institute of Scientific and Technical Information of China (English)

    王志伟; 王小艳; 厉建田; 袁琛; 李伟华

    2011-01-01

    Objective To investigate the value of plasma glutathione S-transferase, D-lactate and creatine kinase levels to the diagnosis of acute intestinal ischemia in Wistar rats. Methods Seventy Wistar rats were randomly divided into seven groups: the sham operation group and six mesentery ischemia groups in 15 minutes, 30 minutes, 1 hour, 1. 5 hours, 2 hours and 3 hours, 10 rats each. The levels of plasma glutathione S-transf erase, D-lactate and creatine kinase were determined in each group in 15 minutes, 30 minutes, 1 hour, 1. 5 hours, 2 hours and 3 hours after isolating superior mesenteric artery and blocking blood flow, and were analyzed their relationship with intestinal injury scores. Results The intestinal injury scores increased with the prolong of ischemia time(P<0. 01). Plasma glutathione S-transferase level was higher in 15 minutes than that in the sham operation group (P<0. 05) and was the highest in 1. 5 hours. Plasma D-lactate level was higher in 1 hour than that in the sham operation group(P<0. 05). Plasma creatine kinase level was higher in 1. 5 hours than that in sham operation group, showed a dramatically increase in 2 hours and kept this tendency from then on. The levels of plasma glutathione S-transferase, D-lactate and creatine kinase were positively correlated with the intestinal injury scores(P<0. 05). Conclusion Plasma glutathione S-transferase and D-lactate may be useful markers of early diagnosis of intestinal ischemia. Increased plasma creatine kinase level indicates an unfavorable prognosis.%目的:探讨血浆谷胱甘肽S转移酶(glutathione S-transferase,GST)、D-乳酸盐(D-lactate,DLA)、肌酸激酶(creatine kinase,CK)在急性小肠缺血性疾病中的诊断价值。方法:70只Wistar大鼠随机分为假手术组以及肠系膜缺血15 min,30 min,1 h,1.5 h,2 h和3 h组,每组10只。分别于游离肠系膜上动脉后即刻以及阻断血流15 min,30 min,1 h,1.5 h,2 h和3 h检测血浆中GST,DLA及CK水

  20. Inhibitors of protein kinase C prevent enhancement of calcium current and action potentials in peptidergic neurons of Aplysia.

    Science.gov (United States)

    Conn, P J; Strong, J A; Kaczmarek, L K

    1989-02-01

    Following brief stimulation of an afferent pathway, the bag cell neurons of Aplysia undergo a dramatic change in excitability, resulting in a prolonged discharge of spontaneous action potentials. During the discharge, the action potentials of the bag cell neurons become enhanced in height and width. The afterdischarge triggers release of neuroactive peptides that initiate egg-laying behavior in this animal. Evidence suggests that changes in excitability of the bag cell neurons may be mediated by activation of protein kinase C (PKC) and cAMP-dependent protein kinase (cAMP-PK). PKC activators, such as the phorbol ester TPA (12-O-tetradecanoyl-13-phorbol acetate), enhance the amplitude of action potentials in isolated bag cell neurons in cell culture. These agents act by unmasking a previously covert species of voltage-dependent calcium channel resulting in an increase in calcium current. In the accompanying paper (Conn et al., 1989), we showed that H-7, a protein kinase inhibitor, inhibits the effect of TPA, and is a selective inhibitor of PKC relative to cAMP-PK in these cells. We now report that another PKC inhibitor, sphinganine, also inhibits the effect of TPA on action potential height and calcium current in cultured bag cell neurons, and that N-acetylsphinganine, an inactive sphinganine analog, fails to inhibit the effects of PKC activators. Although both H-7 and sphinganine prevent the effects of TPA when added prior to TPA addition, neither compound reverses the effects of TPA when added after the action potentials have already become enhanced by TPA.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. RAF kinase activity regulates neuroepithelial cell proliferation and neuronal progenitor cell differentiation during early inner ear development.

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    Marta Magariños

    Full Text Available BACKGROUND: Early inner ear development requires the strict regulation of cell proliferation, survival, migration and differentiation, coordinated by the concerted action of extrinsic and intrinsic factors. Deregulation of these processes is associated with embryonic malformations and deafness. We have shown that insulin-like growth factor I (IGF-I plays a key role in embryonic and postnatal otic development by triggering the activation of intracellular lipid and protein kinases. RAF kinases are serine/threonine kinases that regulate the highly conserved RAS-RAF-MEK-ERK signaling cascade involved in transducing the signals from extracellular growth factors to the nucleus. However, the regulation of RAF kinase activity by growth factors during development is complex and still not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of qRT-PCR, Western blotting, immunohistochemistry and in situ hybridization, we show that C-RAF and B-RAF are expressed during the early development of the chicken inner ear in specific spatiotemporal patterns. Moreover, later in development B-RAF expression is associated to hair cells in the sensory patches. Experiments in ex vivo cultures of otic vesicle explants demonstrate that the influence of IGF-I on proliferation but not survival depends on RAF kinase activating the MEK-ERK phosphorylation cascade. With the specific RAF inhibitor Sorafenib, we show that blocking RAF activity in organotypic cultures increases apoptosis and diminishes the rate of cell proliferation in the otic epithelia, as well as severely impairing neurogenesis of the acoustic-vestibular ganglion (AVG and neuron maturation. CONCLUSIONS/SIGNIFICANCE: We conclude that RAF kinase activity is essential to establish the balance between cell proliferation and death in neuroepithelial otic precursors, and for otic neuron differentiation and axonal growth at the AVG.

  2. Non-aggregating tau phosphorylation by cyclin-dependent kinase 5 contributes to motor neuron degeneration in spinal muscular atrophy.

    Science.gov (United States)

    Miller, Nimrod; Feng, Zhihua; Edens, Brittany M; Yang, Ben; Shi, Han; Sze, Christie C; Hong, Benjamin Taige; Su, Susan C; Cantu, Jorge A; Topczewski, Jacek; Crawford, Thomas O; Ko, Chien-Ping; Sumner, Charlotte J; Ma, Long; Ma, Yong-Chao

    2015-04-15

    Mechanisms underlying motor neuron degeneration in spinal muscular atrophy (SMA), the leading inherited cause of infant mortality, remain largely unknown. Many studies have established the importance of hyperphosphorylation of the microtubule-associated protein tau in various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. However, tau phosphorylation in SMA pathogenesis has yet to be investigated. Here we show that tau phosphorylation on serine 202 (S202) and threonine 205 (T205) is increased significantly in SMA motor neurons using two SMA mouse models and human SMA patient spinal cord samples. Interestingly, phosphorylated tau does not form aggregates in motor neurons or neuromuscular junctions (NMJs), even at late stages of SMA disease, distinguishing it from other tauopathies. Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because tau phosphorylation at these sites is significantly reduced in Cdk5 knock-out mice; genetic knock-out of Cdk5 activating subunit p35 in an SMA mouse model also leads to reduced tau phosphorylation on S202 and T205 in the SMA;p35(-/-) compound mutant mice. In addition, expression of the phosphorylation-deficient tauS202A,T205A mutant alleviates motor neuron defects in a zebrafish SMA model in vivo and mouse motor neuron degeneration in culture, whereas expression of phosphorylation-mimetic tauS202E,T205E promotes motor neuron defects. More importantly, genetic knock-out of tau in SMA mice rescues synapse stripping on motor neurons, NMJ denervation, and motor neuron degeneration in vivo. Altogether, our findings suggest a novel mechanism for SMA pathogenesis in which hyperphosphorylation of non-aggregating tau by Cdk5 contributes to motor neuron degeneration.

  3. The glypiated neuronal cell adhesion molecule contactin/F11 complexes with src-family protein tyrosine kinase Fyn.

    Science.gov (United States)

    Zisch, A H; D'Alessandri, L; Amrein, K; Ranscht, B; Winterhalter, K H; Vaughan, L

    1995-06-01

    Glycosyl phosphatidylinositol-anchored glycoproteins of the immunoglobulin superfamily play an important role in the formation of neuronal networks during development. The mechanism whereby neuronal GPI-linked molecules transduce recognition signals remains to be established. Analysis of detergent-resistant immune-complexes reveals that the glypiated neuronal cell adhesion molecule contactin/F11 specifically complexes with the cytoplasmic, nonreceptor type src-family tyrosine kinase Fyn. Antibody-mediated cross-linking of contactin/F11 on embryonic chick neuronal cells leads to an increase of the Fyn-activity coprecipitated with contactin/F11, and elevates phosphorylation of an additional 75/80 K component within the contactin/F11-immune-complex. Additionally, binding of ligands, i.e., contactin/F11-specific antibody or tenascin-R, a natural ligand of contactin/F11, to the surface of HeLa transfectants expressing contactin/F11, causes capping of contactin/F11 and a concomitant change in the distribution of the intracellular kinase Fyn, thus confirming their physical association. This indicates that contactin/F11-mediated signaling requires Fyn.

  4. SHORT AND LONGER-TERM EFFECTS OF CREATINE SUPPLEMENTATION ON EXERCISE INDUCED MUSCLE DAMAGE

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    John Rosene

    2009-03-01

    Full Text Available The purpose of this investigation was to determine if creatine supplementation assisted with reducing the amount of exercise induced muscle damage and if creatine supplementation aided in recovery from exercise induced muscle damage. Two groups of subjects (group 1 = creatine; group 2 = placebo participated in an eccentric exercise protocol following 7 and 30 days of creatine or placebo supplementation (20 g.d-1 for 7 d followed by 6g.d-1 for 23 d = 30 d. Prior to the supplementation period, measurements were obtained for maximal dynamic strength, maximal isometric force, knee range of motion, muscle soreness, and serum levels of creatine kinase (CK and lactate dehydrogenase (LDH. Following 7 days of creatine supplementation, on day 8, subjects began consuming 6 g.d-1 of creatine for 23 days. Additionally on days 8 and 31, subjects performed an eccentric exercise protocol using the knee extensors to induce muscle damage. Indirect markers of muscle damage, including maximal isometric force, knee range of motion, muscle soreness, and serum levels of CK and LDH, were collected at 12, 24, and 48 hours following each exercise bout. The results indicated that acute bouts of creatine have no effect on indirect markers of muscle damage for the acute (7 days bout. However, maximal isometric force was greater for the creatine group versus placebo for the chronic (30 days bout. This suggests that the ergogenic effect of creatine following 30 days of supplementation may have a positive impact on exercise induced muscle damage

  5. Mixed-lineage kinase inhibitors require the activation of Trk receptors to maintain long-term neuronal trophism and survival.

    Science.gov (United States)

    Wang, Leo H; Paden, Andrew J; Johnson, Eugene M

    2005-03-01

    Small-molecule mixed-lineage kinase (MLK) inhibitors, such as CEP-1347 [3,9-bis[(ethylthio)methyl]-(8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H, 11H-2,7b,11a-triazadibenzo(a,g)cycloocta(cde)trinden-1-one] and CEP-11004 [3,9-bis-[(isopropylthio)methyl]-(8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(cde)trinden-1-one], prevent c-Jun NH(2)-terminal kinase (JNK) pathway activation as well as the consequent neuronal cell death in many cell culture and animal models. In the cell culture model of nerve growth factor (NGF)-deprived sympathetic neurons, we find that CEP-11004 induced a approximately 3-fold increase in the mRNA and protein levels of TrkA, the NGF receptor. This resulted in ligand-independent activation of the TrkA receptor and the downstream phosphatidylinositol 3-kinase (PI3-kinase) pathway. Addition of the Trk inhibitor K252a [(8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(cde)-trinden-1-one] or the PI3-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] significantly decreased the protein synthesis rates, mitochondrial function, and neuronal survival maintained by CEP-11004. In contrast to sympathetic neurons, MLK inhibitors maintain only short-term survival of potassium- and serum-deprived rat cerebellar granule neurons (CGNs), despite continuous inhibition of the JNK pathway. We found that similar to sympathetic neurons, CEP-11004 increased the levels of the Trk receptor expressed in CGNs, TrkB. However, CGNs required the addition of the exogenous ligand brain-derived neurotrophic factor (BDNF) to activate the PI3-kinase pathway and to maintain long-term survival. BDNF activated TrkB, but caused rapid down-regulation of activated receptors and maintained only minimal survival. Therefore, increase in TrkB levels

  6. Nociceptive-induced myocardial remote conditioning is mediated by neuronal gamma protein kinase C.

    Science.gov (United States)

    Gross, Eric R; Hsu, Anna K; Urban, Travis J; Mochly-Rosen, Daria; Gross, Garrett J

    2013-09-01

    Deciphering the remote conditioning molecular mechanism may provide targets to develop therapeutics that can broaden the clinical application. To further investigate this, we tested whether two protein kinase C (PKC) isozymes, the ubiquitously expressed epsilon PKC (εPKC) and the neuronal-specific gamma PKC (γPKC), mediate nociceptive-induced remote myocardial conditioning. Male Sprague-Dawley rats were used for both in vivo and ex vivo myocardial ischemia-reperfusion protocols. For the in vivo studies, using a surgical abdominal incision for comparison, applying only to the abdomen either bradykinin or the εPKC activator (ψεRACK) reduced myocardial infarct size (45 ± 1, 44 ± 2 %, respectively, vs. incision: 43 ± 2 %, and control: 63 ± 2 %, P classical PKC isozyme activator (activating α, β, βII, and γ), reduced myocardial injury. Importantly, the classical PKC isozyme activator given to the abdomen in vivo (with an intact nervous system including γPKC) during myocardial ischemia reduced infarct size as effectively as an abdominal incision or ψεRACK (45 ± 1 vs. 45 ± 2 and 47 ± 1 %, respectively). The classical PKC activator-induced protection was also blocked by spinal cord surgical transection. These findings identified potential remote conditioning mimetics, with these strategies effective even during myocardial ischemia. A novel mechanism of nociceptive-induced remote conditioning, involving γPKC, was also identified.

  7. Opioid-induced mitogen-activated protein kinase signaling in rat enteric neurons following chronic morphine treatment.

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    Celine Duraffourd

    Full Text Available Opioids, acting at μ opioid receptors, are commonly used for pain management. Chronic opioid treatment induces cellular adaptations, which trigger long-term side effects, including constipation mediated by enteric neurons. We tested the hypothesis that chronic opioid treatment induces alterations of μ opioid receptor signaling in enteric neurons, which are likely to serve as mechanisms underlying opioid-induced constipation. In cultured rat enteric neurons, either untreated (naïve or exposed to morphine for 4 days (chronic, we compared the effect of morphine and DAMGO (D-Ala2,MePhe4,Gly-ol5 enkephalin on μ opioid receptor internalization and downstream signaling by examining the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2 (MAPK/ERK pathway, cAMP accumulation and transcription factor cAMP Response Element-Binding protein (CREB expression. μ opioid receptor internalization and MAPK/ERK phosphorylation were induced by DAMGO, but not morphine in naïve neurons, and by both opioids in chronic neurons. MAPK/ERK activation was prevented by the receptor antagonist naloxone, by blocking receptor trafficking with hypertonic sucrose, dynamin inhibitor, or neuronal transfection with mutated dynamin, and by MAPK inhibitor. Morphine and DAMGO inhibited cAMP in naïve and chronic enteric neurons, and induced desensitization of cAMP signaling. Chronic morphine treatment suppressed desensitization of cAMP and MAPK signaling, increased CREB phosphorylation through a MAPK/ERK pathway and induced delays of gastrointestinal transit, which was prevented by MAPK/ERK blockade. This study showed that opioids induce endocytosis- and dynamin-dependent MAPK/ERK activation in enteric neurons and that chronic morphine treatment triggers changes at the receptor level and downstream signaling resulting in MAPK/ERK-dependent CREB activation. Blockade of this signaling pathway prevents the development of gastrointestinal

  8. Thrombin-induced apoptosis in neurons through activation of c-Jun-N-terminal kinase.

    Science.gov (United States)

    Bao, Lei; Zu, Jie; He, Qianqian; Zhao, Hui; Zhou, Su; Ye, Xinchun; Yang, Xinxin; Zan, Kun; Zhang, Zuohui; Shi, Hongjuan; Cui, Guiyun

    2017-01-01

    Studies have shown that thrombin activation played a central role in cell injuries associated with intracerebral hemorrhage (ICH). Here, our study investigated the cytotoxicity of thrombin on neurons, and determined the involvement of JNK pathways in thrombin-induced neuronal apoptosis. Primary cultured neurons were treated with different doses of thrombin. Some neurons were given either SP600125 or vehicle. LDH release assay and flow cytometry were used to measure neuronal apoptosis caused by thrombin. The activation of JNK and capases-3 were measured by Western blot. Our results showed large doses of thrombin that increased the LDH release, the level of cleaved caspase-3 and apoptosis rate of neurons. JNK was activated by thrombin in a time-dependent manner. Administration of SP600125 protects neurons from thrombin-induced apoptosis. These data indicate that the activation of JNK is crucial for thrombin-induced neuronal apoptosis, and inhibition of JNK may be a potential therapeutic target for ICH.

  9. Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats Efeito da administração aguda da cetamina e imipramina sobre a atividade da creatina quinase no encéfalo de ratos

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    Lara C. Assis

    2009-09-01

    Full Text Available OBJECTIVE: Clinical findings suggest that ketamine may be used for the treatment of major depression. The present study aimed to compare behavioral effects and brain Creatine kinase activity in specific brain regions after administration of ketamine and imipramine in rats. METHOD: Rats were acutely given ketamine or imipramine and antidepressant-like activity was assessed by the forced swimming test; Creatine kinase activity was measured in different regions of the brain. RESULTS: The results showed that ketamine (10 and 15mg/kg and imipramine (20 and 30mg/kg reduced immobility time when compared to saline group. We also observed that ketamine (10 and 15mg/kg and imipramine (20 and 30mg/kg increased Creatine kinase activity in striatum and cerebral cortex. Ketamine at the highest dose (15mg/kg and imipramine (20 and 30mg/kg increased Creatine kinase activity in cerebellum and prefrontal cortex. On the other hand, hippocampus was not affected. CONCLUSION: Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, the modulation of energy metabolism (like increase in Creatine kinase activity by antidepressants could be an important mechanism of action of these drugs.OBJETIVO: Vários achados clínicos sugerem que a cetamina apresenta efeito antidepressivo. O presente estudo tem como objetivo comparar efeitos comportamentais e a atividade da creatina quinase em regiões específicas do encéfalo após a administração de cetamina e imipramina em ratos. MÉTODO: Ratos Wistar receberam uma administração aguda de cetamina ou imipramina e a atividade antidepressiva foi avaliada pelo teste de nado forçado; a atividade da creatina quinase foi medida em diferentes regiões encefálicas. RESULTADOS: Os resultados mostraram que a cetamina (10 e 15mg/kg e a imipramina (20 e 30mg/kg diminuíram o tempo de imobilidade quando comparados ao grupo salina. Também foi observado que a cetamina (10 e 15mg/kg e a

  10. Proteolytic activation of proapoptotic kinase protein kinase Cδ by tumor necrosis factor α death receptor signaling in dopaminergic neurons during neuroinflammation

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    Gordon Richard

    2012-04-01

    Full Text Available Abstract Background The mechanisms of progressive dopaminergic neuronal loss in Parkinson’s disease (PD remain poorly understood, largely due to the complex etiology and multifactorial nature of disease pathogenesis. Several lines of evidence from human studies and experimental models over the last decade have identified neuroinflammation as a potential pathophysiological mechanism contributing to disease progression. Tumor necrosis factor α (TNF has recently emerged as the primary neuroinflammatory mediator that can elicit dopaminergic cell death in PD. However, the signaling pathways by which TNF mediates dopaminergic cell death have not been completely elucidated. Methods In this study we used a dopaminergic neuronal cell model and recombinant TNF to characterize intracellular signaling pathways activated during TNF-induced dopaminergic neurotoxicity. Etanercept and neutralizing antibodies to tumor necrosis factor receptor 1 (TNFR1 were used to block TNF signaling. We confirmed the results from our mechanistic studies in primary embryonic mesencephalic cultures and in vivo using the stereotaxic lipopolysaccharide (LPS model of nigral dopaminergic degeneration. Results TNF signaling in dopaminergic neuronal cells triggered the activation of protein kinase Cδ (PKCδ, an isoform of the novel PKC family, by caspase-3 and caspase-8 dependent proteolytic cleavage. Both TNFR1 neutralizing antibodies and the soluble TNF receptor Etanercept blocked TNF-induced PKCδ proteolytic activation. Proteolytic activation of PKCδ was accompanied by translocation of the kinase to the nucleus. Notably, inhibition of PKCδ signaling by small interfering (siRNA or overexpression of a PKCδ cleavage-resistant mutant protected against TNF-induced dopaminergic neuronal cell death. Further, primary dopaminergic neurons obtained from PKCδ knockout (−/− mice were resistant to TNF toxicity. The proteolytic activation of PKCδ in the mouse substantia nigra in the

  11. Cyclin-Dependent Kinase 5 Regulates Dendritic Spine Formation and Maintenance of Cortical Neuron in the Mouse Brain.

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    Mita, Naoki; He, Xiaojuan; Sasamoto, Kodai; Mishiba, Tomohide; Ohshima, Toshio

    2016-03-01

    Cyclin-dependent kinase 5 (Cdk5) activity is dependent on its association with 1 of 2 neuron-specific activators, p35 or p39. Cdk5 and its activators play an important role in brain development as well as higher functions like synaptic plasticity, learning, and memory. Reduction in p35 was reported in postmortem schizophrenia brain, in which reduced dendritic spine density was observed. Previous in vitro experiments have shown that Cdk5 is involved in dendritic spine formation, although in vivo evidence is limited. We examined dendritic spine formation in inducible-p35 conditional knockout (p35 cKO); p39 KO mice. When we deleted the p35 gene either during early postnatal days or at adult stage, we observed reduced spine densities of layer V neurons in the cerebral cortex and CA1 pyramidal neurons in the hippocampus. We further generated CA1-specific p35 conditional knockout (CA1-p35 cKO) mice and also CA1-p35 cKO; p39 KO mice in which have specific deletion of p35 in the CA1 region of hippocampus. We found a greater reduction in spine densities in CA1 pyramidal neurons in CA1-p35 cKO; p39 KO mice than in CA1-p35 cKO mice. These results indicate that dendritic spine formation and neuronal maintenance are dependent on Cdk5 activity.

  12. AP-2α regulates migration of GN-11 neurons via a specific genetic programme involving the Axl receptor tyrosine kinase

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    Orso Francesca

    2009-05-01

    Full Text Available Abstract Background Neuronal migration is a crucial process that allows neurons to reach their correct target location to allow the nervous system to function properly. AP-2α is a transcription factor essential for neural crest cell migration and its mutation results in apoptosis within this cell population, as demonstrated by genetic models. Results We down-modulated AP-2α expression in GN-11 neurons by RNA interference and observe reduced neuron migration following the activation of a specific genetic programme including the Adhesion Related Kinase (Axl gene. We prove that Axl is able to coordinate migration per se and by ChIP and promoter analysis we observe that its transcription is directly driven by AP-2α via the binding to one or more functional AP-2α binding sites present in its regulatory region. Analysis of migration in AP-2α null mouse embryo fibroblasts also reveals an essential role for AP-2α in cell movement via the activation of a distinct genetic programme. Conclusion We show that AP-2α plays an essential role in cell movement via the activation of cell-specific genetic programmes. Moreover, we demonstrate that the AP-2α regulated gene Axl is an essential player in GN-11 neuron migration.

  13. Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases

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    Kelley Matthew

    2009-02-01

    Full Text Available Abstract Background Wnt proteins play roles in many biological processes, including axon guidance and cell migration. In the mammalian hindbrain, facial branchiomotor (FBM neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. In this study, we investigated a possible role of Wnts and the planar cell polarity (PCP pathway in this process. Results Here we demonstrate a novel role for Wnt proteins in guiding FBM neurons during their rostral to caudal migration in the hindbrain. We found that Wnt5a is expressed in a caudalhigh to rostrallow gradient in the hindbrain. Wnt-coated beads chemoattracted FBM neurons to ectopic positions in an explant migration assay. The rostrocaudal FBM migration was moderately perturbed in Wnt5a mutant embryos and severely disrupted in Frizzled3 mutant mouse embryos, and was aberrant following inhibition of Wnt function by secreted Frizzled-related proteins. We also show the involvement of the Wnt/PCP pathway in mammalian FBM neuron migration. Thus, mutations in two PCP genes, Vangl2 and Scribble, caused severe defects in FBM migration. Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins. Conclusion These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process. Molecules of the PCP pathway and the JNK and ROCK kinases also play a role in the FBM migration and are likely mediators of Wnt signalling.

  14. Regulation of extracellular signal-regulated kinase 1/2 inlfuences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yaning Zhao; Jianmin Li; Qiqun Tang; Pan Zhang; Liwei Jing; Changxiang Chen; Shuxing Li

    2014-01-01

    Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These ifndings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and ac-celerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.

  15. Leucine-rich repeat kinase 2 modulates retinoic acid-induced neuronal differentiation of murine embryonic stem cells.

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    Cathrin Schulz

    Full Text Available BACKGROUND: Dominant mutations in the leucine-rich repeat kinase 2 (LRRK2 gene are the most prevalent cause of Parkinson's disease, however, little is known about the biological function of LRRK2 protein. LRRK2 is expressed in neural precursor cells suggesting a role in neurodevelopment. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, differential gene expression profiling revealed a faster silencing of pluripotency-associated genes, like Nanog, Oct4, and Lin28, during retinoic acid-induced neuronal differentiation of LRRK2-deficient mouse embryonic stem cells compared to wildtype cultures. By contrast, expression of neurotransmitter receptors and neurotransmitter release was increased in LRRK2+/- cultures indicating that LRRK2 promotes neuronal differentiation. Consistently, the number of neural progenitor cells was higher in the hippocampal dentate gyrus of adult LRRK2-deficient mice. Alterations in phosphorylation of the putative LRRK2 substrates, translation initiation factor 4E binding protein 1 and moesin, do not appear to be involved in altered differentiation, rather there is indirect evidence that a regulatory signaling network comprising retinoic acid receptors, let-7 miRNA and downstream target genes/mRNAs may be affected in LRRK2-deficient stem cells in culture. CONCLUSION/SIGNIFICANCE: Parkinson's disease-linked LRRK2 mutations that associated with enhanced kinase activity may affect retinoic acid receptor signaling during neurodevelopment and/or neuronal maintenance as has been shown in other mouse models of chronic neurodegenerative diseases.

  16. Essential role of neuron-enriched diacylglycerol kinase (DGK), DGKbeta in neurite spine formation, contributing to cognitive function.

    Science.gov (United States)

    Shirai, Yasuhito; Kouzuki, Takeshi; Kakefuda, Kenichi; Moriguchi, Shigeki; Oyagi, Atsushi; Horie, Kyoji; Morita, Shin-ya; Shimazawa, Masamitsu; Fukunaga, Kohji; Takeda, Junji; Saito, Naoaki; Hara, Hideaki

    2010-07-15

    Diacylglycerol (DG) kinase (DGK) phosphorylates DG to produce phosphatidic acid (PA). Of the 10 subtypes of mammalian DGKs, DGKbeta is a membrane-localized subtype and abundantly expressed in the cerebral cortex, hippocampus, and caudate-putamen. However, its physiological roles in neurons and higher brain function have not been elucidated. We, therefore, developed DGKbeta KO mice using the Sleeping Beauty transposon system, and found that its long-term potentiation in the hippocampal CA1 region was reduced, causing impairment of cognitive functions including spatial and long-term memories in Y-maze and Morris water-maze tests. The primary cultured hippocampal neurons from KO mice had less branches and spines compared to the wild type. This morphological impairment was rescued by overexpression of DGKbeta. In addition, overexpression of DGKbeta in SH-SY5Y cells or primary cultured mouse hippocampal neurons resulted in branch- and spine-formation, while a splice variant form of DGKbeta, which has kinase activity but loses membrane localization, did not induce branches and spines. In the cells overexpressing DGKbeta but not the splice variant form, DGK product, PA, was increased and the substrate, DG, was decreased on the plasma membrane. Importantly, lower spine density and abnormality of PA and DG contents in the CA1 region of the KO mice were confirmed. These results demonstrate that membrane-localized DGKbeta regulates spine formation by regulation of lipids, contributing to the maintenance of neural networks in synaptic transmission of cognitive processes including memory.

  17. The Analysis Of The Change Of Serum Creatine Kinase After Resistance Training%抗阻训练引起血清肌酸激酶变化的分析

    Institute of Scientific and Technical Information of China (English)

    潘梅兵; 孙朋

    2012-01-01

    To explore the change of serum creatine kinase after resistance training, elite male kayak athletes in Anhui province are conducted as the subjects, the study is arranged to continue a resistance training for eight weeks. The results showed that the resistance training, when it was started in preparatory stage, ath- letes serum CK activity kept the same in the nomal condition; when in the muscle hypertrophy in ihe stage of training and strength training, serum CK activity ( during the first week and the forth week ) was increased substantially compared with preparatory stage, all have significant difference ( P 〈 0.01 }, which indicates that strength is increasing, considering the training goal. With the subjects adapting themselves to the training intensity, the second and third week and the first week ( P 〈 0.05 }, the fifth week, the sixth week and the fourth week ( P d0.05) compared with CK activity gradually reducing, the results can explain the subjects can produce certain to adapt to the training intensity. In the strength endurance training phase, the seventh and eighth week's testing CK enzyme activity makes no significant difference ( P 〉0.05), which can ex- plain the adaptation.%为探讨抗阻训练后血清肌酸激酶的变化情况,以安徽省优秀男子皮艇运动员为研究对象,进行为期8周的抗阻训练。结果表明,在通过8周抗阻训练后,开始准备阶段,运动员血清CK的活性与正常人无差异;在肌肉肥大训练阶段和肌力训练,血清CK活肚在第1周、第4周都大幅度上升,与准备阶段相比,均有显著性差异(P〈0.01),说明强度为大强度,符合训练目的。随着机体对训练强度的适应,第2、3周和第1周(P〈0.05)、第5周、第6周和第4周(P〈0.05)相比CK活性逐渐降低,说明机体对训练强度产生一定的适应。力量耐力训练阶段,第7、第8周CK酶活性和准备阶段相比,无显著差异(P〉0

  18. The establishment of pediatric reference intervals for creatine kinase-MB and troponin Ⅰ%肌钙蛋白Ⅰ和肌酸激酶同工酶儿童参考区间的建立

    Institute of Scientific and Technical Information of China (English)

    李怀远; 蒋黎敏; 郑建新; 孙璇; 傅启华

    2012-01-01

    Objective To establish the pediatric reference intervals for Troponin Ⅰ and Creatine kinase-MB (CK-MB).Methods Healthy children (223 boys and 162 girls) aged from 7 months to 12 years old were studied.Blood specimens were collected and centrifuged,all serum samples were kept refrigerated below-70 ℃.Troponin Ⅰ and CK-MB were measured on the UniCel DxI 800 immunoassay system (Beckman Coulter) on the same day.Nonparametric statistics was used to estimate the 99th percentile reference intervals.Results The children were divided into three groups (group A 128 cases; group B 128 cases;group C 129 cases) according to age.The upper reference limits for CK-MB were dependent of age,and the group A (7 months-1 years) was shown to be 13.41 μg/L,the group B (2-3 years) was shown to be 9.35 μg/L,the group C (4-12 years) was shown to be 5.48 μg/L.The upper reference limit for Troponin Ⅰ was independent of age or gender and shown to be 0.01 μg/L among 385 children.Conclusions Pediatric reference intervals for Troponin Ⅰ and CK-MB have been defined in healthy children at a relevant age group (7 months-12 years).It is effective for clinical diagnosis and treatment of myocardial damage for children by determining reference intervals for Troponin Ⅰ and CK-MB.%目的 建立肌钙蛋白Ⅰ(Troponin Ⅰ)和肌酸激酶同工酶(CK-MB)儿童参考区间.方法 2011年8-12月收集上海儿童医学中心年龄7个月至12岁健康体检儿童385名,其中男223名,女162名.血液收集后离心,血清-70℃冷冻保存,使用贝克曼库尔特UniCel DxI 800免疫分析系统同一天集中测定结果.以非参数法计算99%参考区间.结果 Troponin Ⅰ共385例,不按年龄和性别划分的参考区间上限值为0.01μg/L.CK-MB按年龄划分的参考区间上限值为:A组(7个月~1岁)128例:13.41μg/L;B组(2~3岁)128例:9.35 μg/L;C组(4~12岁)129例:5.48 μg/L.结论 确定了本院实验室健康儿童(7个月~12岁)Troponin Ⅰ和按年龄分组CK

  19. Phorbol ester reduces ethanol excitation of dopaminergic neurons of the ventral tegmental area: Involvement of protein kinase C theta

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    Sudarat eNimitvilai

    2013-12-01

    Full Text Available Neurons of the ventral tegmental area (VTA play a key role in the rewarding and reinforcing effects of drugs of abuse, including alcohol. Ethanol directly increases the firing rate of dopaminergic (DAergic VTA neurons, but modulation of the firing rate of DAergic VTA neurons can be controlled by a number of factors, including some that are under the control of protein kinase C (PKC. Application of phorbol esters activates PKC and the present study assessed the effect of a phorbol ester, phorbol 12-myristate 13-acetate (PMA, on ethanol-induced excitation of DA VTA neurons. Ethanol-induced excitation of DAergic VTA neurons was reduced significantly in the presence of PMA. This action of PMA was antagonized by chelerythrine chloride, a non-selective antagonist of PKC, but not by moderate concentrations of antagonists of conventional PKC isoforms (Gö6976 and Gö6983. A PKC δ/θ inhibitor antagonized PMA-induced reduction of ethanol excitation. Since PKCδ antagonist Gö6983 did not antagonize the effect of PMA on ethanol excitation, the PMA reduction of ethanol excitation is most likely to be mediated by PKCθ. Antagonists of intracellular calcium pathways were ineffective in antagonizing PMA action on ethanol excitation, consistent with the lack of calcium dependence of PKCθ. In summary, ethanol-induced excitation of VTA neurons is attenuated in the presence of PMA, and this attenuation appears to be mediated by PKCθ. This novel mechanism for interfering with ethanol activation of reward-related neurons could provide a new target for pharmacotherapy to ameliorate alcoholism.

  20. Role of Glycogen Synthase Kinase-3β in APP Hyperphosphorylation Induced by NMDA Stimulation in Cortical Neurons

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    Xanthi Antoniou

    2010-01-01

    Full Text Available The phosphorylation of Amyloid Precursor Protein (APP at Thr668 plays a key role in APP metabolism that is highly relevant to AD. The c-Jun-N-terminal kinase (JNK, glycogen synthase kinase-3β (GSK-3β and cyclin-dependent kinase 5 (Cdk5 can all be responsible for this phosphorylation. These kinases are activated by excitotoxic stimuli fundamental hallmarks of AD. The exposure of cortical neurons to a high dose of NMDA (100 μM for 30’-45’ led to an increase of P-APP Thr668. During NMDA stimulation APP hyperphosphorylation has to be assigned to GSK-3β activity, since addition of L803-mts, a substrate competitive inhibitor of GSK-3β reduced APP phosphorylation induced by NMDA. On the contrary, inhibition of JNK and Cdk5 with D-JNKI1 and Roscovitine respectively did not prevent NMDA-induced P-APP increase. These data show a tight connection, in excitotoxic conditions, between APP metabolism and the GSK-3β signaling pathway.

  1. Enzymes of creatine biosynthesis, arginine and methionine metabolism in normal and malignant cells.

    Science.gov (United States)

    Bera, Soumen; Wallimann, Theo; Ray, Subhankar; Ray, Manju

    2008-12-01

    The creatine/creatine kinase system decreases drastically in sarcoma. In the present study, an investigation of catalytic activities, western blot and mRNA expression unambiguously demonstrates the prominent expression of the creatine-synthesizing enzymes l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase in sarcoma, Ehrlich ascites carcinoma and Sarcoma 180 cells, whereas both enzymes were virtually undetectable in normal muscle. Compared to that of normal animals, these enzymes remained unaffected in the kidney or liver of sarcoma-bearing mice. High activity and expression of mitochondrial arginase II in sarcoma indicated increased ornithine formation. Slightly or moderately higher levels of ornithine, guanidinoacetate and creatinine were observed in sarcoma compared to muscle. Despite the intrinsically low level of creatine in Ehrlich ascites carcinoma and Sarcoma 180 cells, these cells could significantly take up and release creatine, suggesting a functional creatine transport, as verified by measuring mRNA levels of creatine transporter. Transcript levels of arginase II, ornithine-decarboxylase, S-adenosyl-homocysteine hydrolase and methionine-synthase were significantly upregulated in sarcoma and in Ehrlich ascites carcinoma and Sarcoma 180 cells. Overall, the enzymes related to creatine and arginine/methionine metabolism were found to be significantly upregulated in malignant cells. However, the low levels of creatine kinase in the same malignant cells do not appear to be sufficient for the building up of an effective creatine/phosphocreatine pool. Instead of supporting creatine biosynthesis, l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase appear to be geared to support cancer cell metabolism in the direction of polyamine and methionine synthesis because both these compounds are in high demand in proliferating cancer cells.

  2. 大强度离心运动大鼠不同时相骨骼肌结构及血白细胞介素6、肌酸激酶、肌酸激酶同工酶的变化%Skeletal muscle structure at different phases after eccentric exercise and changes of blood interleukin-6, creatine kinase and creatine kinase isoenzyme in rats

    Institute of Scientific and Technical Information of China (English)

    华冰; 董柔; 苏全生

    2009-01-01

    -induced muscle damage, thereby to avoid delayed onset muscle soreness. At present, experimental research is scarce that apply intedeukin-6 (IL-6), creatine kinase (CK) and creatine kinase isoenzyme (CK-MM) to evaluate skeletal muscle damage.OBJECTIVE: To observe the effects of exercise precondiUoning on muscle damage at different phases after eccentric exercise and changes of blood IL-6, CK and CK-MM.DESIGN, TIME AND SETTING: The randomized control animal expedmant was carded out in the Animal Laboratory of Chengdu Sports University between 2006 and 2007. MATERIALS: Eighty female adult SD rats, weighing (231.3+12.44) g, were adopted. Eighty rats were randomly divided into without exercise preconditioning group (n=40) and exercise preconditioning group (n=40). Each group was assigned into 5 subsets, termed before exercise, immediately after exercise, 24, 48, 72 hours after exercise, with 8 rats in each subset. METHODS: Except before exercise subset, other rats in the without exercise preconditioning group were forced to do treadmill exercise (19-21 m/min, -16° incline, 90 minutes). All rats of exercise preconditioning group were forced to do eccentric treadmill exercise for two weeks. After two weeks, treadmill test was made for rats except before exercise subset. MAIN OUTCOME MEASURES: Soleus muscle structure, blood IL-6, CK and CK-MM immediately, 24, 48, 72 hours after eccentric exercise.RESULTS: The soleus muscle was damaged after exercise, especially in without exercise preconditioning group at 24-48 hours after exercise. Blood IL-6 of without exercise preconditioning group increased significantly immediately after exercise and then gradually decreased, but again raised at 72 hours after exercise. In the exercise preconditioning group, blood IL-6 slightly reduced immediately after exercise and then gradually increased. Peak value appeared at 48 hours. After exercise, IL-6 of exercise preconditioning group was obviously lower than that of without exercise preconditioning

  3. Shiga toxin type-2 (Stx2 induces glutamate release via phosphoinositide 3-kinase (PI3K pathway in murine neurons.

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    Fumiko eObata

    2015-07-01

    Full Text Available Shiga toxin-producing Escherichia coli (STEC can cause central nervous system (CNS damage resulting in paralysis, seizures, and coma. The key STEC virulence factors associated with systemic illness resulting in CNS impairment are Shiga toxins (Stx. While neurons express the Stx receptor globotriaosylceramide (Gb3 in vivo, direct toxicity to neurons by Stx has not been studied. We used murine neonatal neuron cultures to study the interaction of Shiga toxin type 2 (Stx2 with cell surface expressed Gb3. Single molecule imaging three dimensional STochastic Optical Reconstruction Microscopy - Total Internal Reflection Fluorescence (3D STORM-TIRF allowed visualization and quantification of Stx2-Gb3 interactions. Furthermore, we demonstrate that Stx2 increases neuronal cytosolic Ca2+, and NMDA-receptor inhibition blocks Stx2-induced Ca2+ influx, suggesting that Stx2-mediates glutamate release. Phosphoinositide 3-kinase (PI3K-specific inhibition by Wortmannin reduces Stx2-induced intracellular Ca2+ indicating that the PI3K signaling pathway may be involved in Stx2-associated glutamate release, and that these pathways may contribute to CNS impairment associated with STEC infection.

  4. Regulation of Extrasynaptic GABAA α4 Receptors by Ethanol-Induced Protein Kinase A, but Not Protein Kinase C Activation in Cultured Rat Cerebral Cortical Neurons.

    Science.gov (United States)

    Carlson, Stephen L; Bohnsack, J Peyton; Patel, Vraj; Morrow, A Leslie

    2016-01-01

    Ethanol produces changes in GABAA receptor trafficking and function that contribute to ethanol dependence symptomatology. Extrasynaptic γ-aminobutyric acid A receptors (GABAA-R) mediate inhibitory tonic current and are of particular interest because they are potentiated by physiologically relevant doses of ethanol. Here, we isolate GABAA α4δ receptors by western blotting in subsynaptic fractions to investigate protein kinase A (PKA) and protein kinase C (PKC) modulation of ethanol-induced receptor trafficking, while extrasynaptic receptor function is determined by measurement of tonic inhibition and responses evoked by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). Rat cerebral cortical neurons were grown for 18 days in vitro and exposed to ethanol and/or PKA/PKC modulators. Ethanol exposure (1 hour) did not alter GABAA α4 receptor abundance, but it increased tonic current amplitude, an effect that was prevented by inhibiting PKA, but not PKC. Direct activation of PKA, but not PKC, increased the abundance and tonic current of extrasynaptic α4δ receptors. In contrast, prolonged ethanol exposure (4 hours) reduced α4δ receptor abundance as well as tonic current, and this effect was also PKA dependent. Finally, PKC activation by ethanol or phorbol-12,13-dibutyrate (PdBu) had no effect on extrasynaptic α4δ subunit abundance or activity. We conclude that ethanol alters extrasynaptic α4δ receptor function and expression in cortical neurons in a PKA-dependent manner, but ethanol activation of PKC does not influence these receptors. These results could have clinical relevance for therapeutic strategies to restore normal GABAergic functioning for the treatment of alcohol use disorders.

  5. Downstream of tyrosine kinase/docking protein 6, as a novel substrate of tropomyosin-related kinase C receptor, is involved in neurotrophin 3-mediated neurite outgrowth in mouse cortex neurons

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    Yuan Jian

    2010-06-01

    Full Text Available Abstract Background The downstream of tyrosine kinase/docking protein (Dok adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase. The tropomyosin-related kinase (Trk receptor family, which has three members (TrkA, TrkB and TrkC, are receptor tyrosine kinases that play pivotal roles in many stages of nervous system development, such as differentiation, migration, axon and dendrite projection and neuron patterning. Upon related neurotrophin growth factor stimulation, dimerisation and autophosphorylation of Trk receptors can occur, recruiting adaptor proteins to mediate signal transduction. Results In this report, by using yeast two-hybrid assays, glutathione S-transferase (GST precipitation assays and coimmunoprecipitation (Co-IP experiments, we demonstrate that Dok6 selectively binds to the NPQY motif of TrkC through its phosphotyrosine-binding (PTB domain in a kinase activity-dependent manner. We further confirmed their interaction by coimmunoprecipitation and colocalisation in E18.5 mouse cortex neurons, which provided more in vivo evidence. Next, we demonstrated that Dok6 is involved in neurite outgrowth in mouse cortex neurons via the RNAi method. Knockdown of Dok6 decreased neurite outgrowth in cortical neurons upon neurotrophin 3 (NT-3 stimulation. Conclusions We conclude that Dok6 interacts with the NPQY motif of the TrkC receptor through its PTB domain in a kinase activity-dependent manner, and works as a novel substrate of the TrkC receptor involved in NT-3-mediated neurite outgrowth in mouse cortex neurons.

  6. Specific effects of c-Jun NH2-terminal kinase-interacting protein 1 in neuronal axons

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    Shu Tang

    2016-01-01

    Full Text Available c-Jun NH2-terminal kinase (JNK-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B (TrkB anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of TrkB anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neurons in vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed TrkB complexes in vitro and in vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of TrkB gradually increased in axon terminals. However, the distribution of TrkB reduced in axon terminals after knocking out JNK-interacting protein 1. In addition, there were differences in distribution of TrkB after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of TrkB in dendrites. These findings confirm that JNK-interacting protein 1 can interact with TrkB in neuronal cells, and can regulate the transport of TrkB in axons, but not in dendrites.

  7. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation.

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    Turner, Clare E; Byblow, Winston D; Gant, Nicholas

    2015-01-28

    Impairment or interruption of oxygen supply compromises brain function and plays a role in neurological and neurodegenerative conditions. Creatine is a naturally occurring compound involved in the buffering, transport, and regulation of cellular energy, with the potential to replenish cellular adenosine triphosphate without oxygen. Creatine is also neuroprotective in vitro against anoxic/hypoxic damage. Dietary creatine supplementation has been associated with improved symptoms in neurological disorders defined by impaired neural energy provision. Here we investigate, for the first time in humans, the utility of creatine as a dietary supplement to protect against energetic insult. The aim of this study was to assess the influence of oral creatine supplementation on the neurophysiological and neuropsychological function of healthy young adults during acute oxygen deprivation. Fifteen healthy adults were supplemented with creatine and placebo treatments for 7 d, which increased brain creatine on average by 9.2%. A hypoxic gas mixture (10% oxygen) was administered for 90 min, causing global oxygen deficit and impairing a range of neuropsychological processes. Hypoxia-induced decrements in cognitive performance, specifically attentional capacity, were restored when participants were creatine supplemented, and corticomotor excitability increased. A neuromodulatory effect of creatine via increased energy availability is presumed to be a contributing factor of the restoration, perhaps by supporting the maintenance of appropriate neuronal membrane potentials. Dietary creatine monohydrate supplementation augments neural creatine, increases corticomotor excitability, and prevents the decline in attention that occurs during severe oxygen deficit. This is the first demonstration of creatine's utility as a neuroprotective supplement when cellular energy provision is compromised.

  8. Regulation of autophagy by AMP-activated protein kinase/ sirtuin 1 pathway reduces spinal cord neurons damage

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    Peng Yan

    2017-09-01

    Full Text Available Objective(s: AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1 signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT1 pathway on autophagy after spinal cord injury (SCI. Materials and Methods:The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI in vitro. The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining. Results: We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma in vivo and in vitro, indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma in vivo and in vitro. Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI. Conclusion: Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.

  9. Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation.

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    Bye, Nicole; Christie, Kimberly J; Turbic, Alisa; Basrai, Harleen S; Turnley, Ann M

    2016-05-01

    Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4 weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35 days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury.

  10. Essential role of neuron-enriched diacylglycerol kinase (DGK, DGKbeta in neurite spine formation, contributing to cognitive function.

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    Yasuhito Shirai

    Full Text Available BACKGROUND: Diacylglycerol (DG kinase (DGK phosphorylates DG to produce phosphatidic acid (PA. Of the 10 subtypes of mammalian DGKs, DGKbeta is a membrane-localized subtype and abundantly expressed in the cerebral cortex, hippocampus, and caudate-putamen. However, its physiological roles in neurons and higher brain function have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We, therefore, developed DGKbeta KO mice using the Sleeping Beauty transposon system, and found that its long-term potentiation in the hippocampal CA1 region was reduced, causing impairment of cognitive functions including spatial and long-term memories in Y-maze and Morris water-maze tests. The primary cultured hippocampal neurons from KO mice had less branches and spines compared to the wild type. This morphological impairment was rescued by overexpression of DGKbeta. In addition, overexpression of DGKbeta in SH-SY5Y cells or primary cultured mouse hippocampal neurons resulted in branch- and spine-formation, while a splice variant form of DGKbeta, which has kinase activity but loses membrane localization, did not induce branches and spines. In the cells overexpressing DGKbeta but not the splice variant form, DGK product, PA, was increased and the substrate, DG, was decreased on the plasma membrane. Importantly, lower spine density and abnormality of PA and DG contents in the CA1 region of the KO mice were confirmed. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that membrane-localized DGKbeta regulates spine formation by regulation of lipids, contributing to the maintenance of neural networks in synaptic transmission of cognitive processes including memory.

  11. Integrin-linked kinase modulates longevity and thermotolerance in C. elegans through neuronal control of HSF-1.

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    Kumsta, Caroline; Ching, Tsui-Ting; Nishimura, Mayuko; Davis, Andrew E; Gelino, Sara; Catan, Hannah H; Yu, Xiaokun; Chu, Chu-Chiao; Ong, Binnan; Panowski, Siler H; Baird, Nathan; Bodmer, Rolf; Hsu, Ao-Lin; Hansen, Malene

    2014-06-01

    Integrin-signaling complexes play important roles in cytoskeletal organization and cell adhesion in many species. Components of the integrin-signaling complex have been linked to aging in both Caenorhabditis elegans and Drosophila melanogaster, but the mechanism underlying this function is unknown. Here, we investigated the role of integrin-linked kinase (ILK), a key component of the integrin-signaling complex, in lifespan determination. We report that genetic reduction of ILK in both C. elegans and Drosophila increased resistance to heat stress, and led to lifespan extension in C. elegans without majorly affecting cytoskeletal integrity. In C. elegans, longevity and thermotolerance induced by ILK depletion was mediated by heat-shock factor-1 (HSF-1), a major transcriptional regulator of the heat-shock response (HSR). Reduction in ILK levels increased hsf-1 transcription and activation, and led to enhanced expression of a subset of genes with roles in the HSR. Moreover, induction of HSR-related genes, longevity and thermotolerance caused by ILK reduction required the thermosensory neurons AFD and interneurons AIY, which are known to play a critical role in the canonical HSR. Notably, ILK was expressed in neighboring neurons, but not in AFD or AIY, implying that ILK reduction initiates cell nonautonomous signaling through thermosensory neurons to elicit a noncanonical HSR. Our results thus identify HSF-1 as a novel effector of the organismal response to reduced ILK levels and show that ILK inhibition regulates HSF-1 in a cell nonautonomous fashion to enhance stress resistance and lifespan in C. elegans.

  12. Structural correlates of the creatine transporter function regulation: the undiscovered country.

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    Santacruz, Lucia; Jacobs, Danny O

    2016-08-01

    Creatine (Cr) and phosphocreatine constitute an energy shuttle that links ATP production in mitochondria to subcellular locations of ATP consumption. Cells in tissues that are reliant on this energy shuttle, such as myocytes and neurons, appear to have very limited ability to synthesize creatine. Therefore, these cells depend on Cr uptake across the cell membrane by a specialized creatine transporter (CrT solute carrier SLC6A8) in order to maintain intracellular creatine levels. Cr supplementation has been shown to have a beneficial effect in numerous in vitro and in vivo models, particularly in cases of oxidative stress, and is also widely used by athletes as a performance enhancement nutraceutical. Intracellular creatine content is maintained within narrow limits. However, the physiological and cellular mechanisms that mediate Cr transport during health and disease (such as cardiac failure) are not understood. In this narrative mini-review, we summarize the last three decades of research on CrT structure, function and regulation.

  13. Extracellular creatine regulates creatine transport in rat and human muscle cells.

    OpenAIRE

    1988-01-01

    Muscle cells do not synthesize creatine; they take up exogenous creatine by specific Na+-dependent plasma membrane transporters. We found that extracellular creatine regulates the level of expression of these creatine transporters in L6 rat muscle cells. L6 myoblasts maintained for 24 hr in medium containing 1 mM creatine exhibited 1/3rd of the creatine transport activity of cells maintained for 24 hr in medium without creatine. Down-regulation of creatine transport was partially reversed whe...

  14. Homocysteine induces energy imbalance in rat skeletal muscle: is creatine a protector?

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    Kolling, Janaína; Scherer, Emilene B S; Siebert, Cassiana; Hansen, Fernanda; Torres, Felipe V; Scaini, Giselli; Ferreira, Gabriela; de Andrade, Rodrigo B; Gonçalves, Carlos A S; Streck, Emílio L; Wannmacher, Clovis M D; Wyse, Angela T S

    2013-10-01

    Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions.

  15. Creatine supplementation does not reduce muscle damage or enhance recovery from resistance exercise.

    Science.gov (United States)

    Rawson, Eric S; Conti, Michael P; Miles, Mary P

    2007-11-01

    Previous studies have shown that creatine supplementation reduces muscle damage and inflammation following running but not following high-force, eccentric exercise. Although the mechanical strain placed on muscle fibers during high-force, eccentric exercise may be too overwhelming for creatine to exert any protective effect, creatine supplementation may protect skeletal muscle stressed by a resistance training challenge that is more hypoxic in nature. The purpose of this study was to examine the effects of short-term creatine supplementation on markers of muscle damage (i.e., strength, range of motion, muscle soreness, muscle serum protein activity, C-reactive protein) to determine whether creatine supplementation offers protective effects on skeletal muscle following a hypoxic resistance exercise test. Twenty-two healthy, weight-trained men (19-27 years) ingested either creatine or a placebo for 10 days. Following 5 days of supplementation, subjects performed a squat exercise protocol (5 sets of 15-20 repetitions at 50% of 1 repetition maximum [1RM]). Assessments of creatine kinase (CK) and lactate dehydrogenase activity, high-sensitivity C-reactive protein, maximal strength, range of motion (ROM), and muscle soreness (SOR) with movement and palpation were conducted pre-exercise and during a 5-day follow up. Following the exercise test, maximal strength and ROM decreased, whereas SOR and CK increased. Creatine and placebo-supplemented subjects experienced significant decreases in maximal strength (creatine: 13.4 kg, placebo: 17.5 kg) and ROM (creatine: 2.4 degrees , placebo: 3.0 degrees ) immediately postexercise, with no difference between groups. Following the exercise test, there were significant increases in SOR with movement and palpation (p creatine supplementation does not reduce skeletal muscle damage or enhance recovery following a hypoxic resistance exercise challenge.

  16. Creatine supplementation: can it improve quality of life in the elderly without associated resistance training?

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    Moon, Anna; Heywood, Lara; Rutherford, Stephen; Cobbold, Christian

    2013-12-01

    Ageing is associated with decreased muscle mass, strength, power and function, and reduction in bone density and mineral content, leading to reduced independence and increased risk of falls. Creatine supplementation is reported to improve muscular strength and performance with training in younger athletes, and therefore could benefit older individuals. This review critically appraises the current literature on whether creatine supplementation enhances muscular performance and function, body composition, bone mineral density and content in older adults without the addition of resistance training, and thus determines whether creatine supplementation can lead to an improved lifestyle for the sedentary elderly population. There is conflicting evidence regarding the usefulness of creatine supplementation in older subjects. Generally, however, creatine supplementation, without associated resistance training, seems to enhance muscular strength, power and endurance, increase lean body mass (LBM) and improve the functional capacity of the elderly. Furthermore, it has been demonstrated that increased muscle mass due to creatine supplementation can result in increased local bone density. It appears that the effect of creatine supplementation is more beneficial in larger muscles and less effective in smaller muscles, however there are exceptions. The mechanism by which creatine supplementation works requires further research, however it is likely that the effects of creatine are related to creatine kinase activity, providing enhanced energy production for greater muscular contraction. These data indicate that creatine supplementation without associated training in the elderly could potentially delay atrophy of muscle mass, improve endurance and strength, and increase bone strength, and thus may be a safe therapeutic strategy to help decrease loss in functional performance of everyday tasks.

  17. Myocardial creatine levels do not influence response to acute oxidative stress in isolated perfused heart.

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    Dunja Aksentijević

    Full Text Available Multiple studies suggest creatine mediates anti-oxidant activity in addition to its established role in cellular energy metabolism. The functional significance for the heart has yet to be established, but antioxidant activity could contribute to the cardioprotective effect of creatine in ischaemia/reperfusion injury.To determine whether intracellular creatine levels influence responses to acute reactive oxygen species (ROS exposure in the intact beating heart. We hypothesised that mice with elevated creatine due to over-expression of the creatine transporter (CrT-OE would be relatively protected, while mice with creatine-deficiency (GAMT KO would fare worse.CrT-OE mice were pre-selected for creatine levels 20-100% above wild-type using in vivo (1H-MRS. Hearts were perfused in isovolumic Langendorff mode and cardiac function monitored throughout. After 20 min equilibration, hearts were perfused with either H2O2 0.5 µM (30 min, or the anti-neoplastic drug doxorubicin 15 µM (100 min. Protein carbonylation, creatine kinase isoenzyme activities and phospho-PKCδ expression were quantified in perfused hearts as markers of oxidative damage and apoptotic signalling. Wild-type hearts responded to ROS challenge with a profound decline in contractile function that was ameliorated by co-administration of catalase or dexrazoxane as positive controls. In contrast, the functional deterioration in CrT-OE and GAMT KO hearts was indistinguishable from wild-type controls, as was the extent of oxidative damage and apoptosis. Exogenous creatine supplementation also failed to protect hearts from doxorubicin-induced dysfunction.Intracellular creatine levels do not influence the response to acute ROS challenge in the intact beating heart, arguing against creatine exerting (patho-physiologically relevant anti-oxidant activity.

  18. Dihydromyricetin protects neurons in an MPTP-induced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity

    Science.gov (United States)

    Ren, Zhao-xiang; Zhao, Ya-fei; Cao, Ting; Zhen, Xue-chu

    2016-01-01

    Aim: It is general believed that mitochondrial dysfunction and oxidative stress play critical roles in the pathology of Parkinson's disease (PD). Dihydromyricetin (DHM), a natural flavonoid extracted from Ampelopsis grossedentata, has recently been found to elicit potent anti-oxidative effects. In the present study, we explored the role of DHM in protecting dopaminergic neurons. Methods: Male C57BL/6 mice were intraperitoneally injected with 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 d to induce PD. Additionally, mice were treated with either 5 or 10 mg/kg DHM for a total of 13 d (3 d before the start of MPTP, during MPTP administration (7 d) and 3 d after the end of MPTP). For the saline or DHM alone treatment groups, mice were injected with saline or DHM for 13 d. On d 14, behavioral tests (locomotor activity, the rotarod test and the pole test) were administered. After the behavioral tests, the mice were sacrificed, and brain tissue was collected for immunofluorescence staining and Western blotting. In addition, MES23.5 cells were treated with MPP+ and DHM, and evaluated using cell viability assays, reactive oxygen species (ROS) measurements, apoptosis analysis and Western blotting. Results: DHM significantly attenuated MPTP-induced mouse behavioral impairments and dopaminergic neuron loss. In the MES23.5 cells, DHM attenuated MPP+-induced cell injury and ROS production in a dose-dependent manner. In addition, DHM increased glycogen synthase kinase-3 beta phosphorylation in a dose- and time-dependent manner, which may be associated with DHM-induced dopaminergic neuronal protection. Conclusion: The present study demonstrated that DHM is a potent neuroprotective agent for DA neurons by modulating the Akt/GSK-3β pathway, which suggests that DHM may be a promising therapeutic candidate for PD. PMID:27374489

  19. The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation.

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    Soppa, Ulf; Schumacher, Julian; Florencio Ortiz, Victoria; Pasqualon, Tobias; Tejedor, Francisco J; Becker, Walter

    2014-01-01

    A fundamental question in neurobiology is how the balance between proliferation and differentiation of neuronal precursors is maintained to ensure that the proper number of brain neurons is generated. Substantial evidence implicates DYRK1A (dual specificity tyrosine-phosphorylation-regulated kinase 1A) as a candidate gene responsible for altered neuronal development and brain abnormalities in Down syndrome. Recent findings support the hypothesis that DYRK1A is involved in cell cycle control. Nonetheless, how DYRK1A contributes to neuronal cell cycle regulation and thereby affects neurogenesis remains poorly understood. In the present study we have investigated the mechanisms by which DYRK1A affects cell cycle regulation and neuronal differentiation in a human cell model, mouse neurons, and mouse brain. Dependent on its kinase activity and correlated with the dosage of overexpression, DYRK1A blocked proliferation of SH-SY5Y neuroblastoma cells within 24 h and arrested the cells in G₁ phase. Sustained overexpression of DYRK1A induced G₀ cell cycle exit and neuronal differentiation. Furthermore, we provide evidence that DYRK1A modulated protein stability of cell cycle-regulatory proteins. DYRK1A reduced cellular Cyclin D1 levels by phosphorylation on Thr286, which is known to induce proteasomal degradation. In addition, DYRK1A phosphorylated p27(Kip1) on Ser10, resulting in protein stabilization. Inhibition of DYRK1A kinase activity reduced p27(Kip1) Ser10 phosphorylation in cultured hippocampal neurons and in embryonic mouse brain. In aggregate, these results suggest a novel mechanism by which overexpression of DYRK1A may promote premature neuronal differentiation and contribute to altered brain development in Down syndrome.

  20. The protein tyrosine kinase inhibitor, genistein, decreases the excitability of capsaicin-sensitive neurons

    Institute of Scientific and Technical Information of China (English)

    L.Liu; FuHui; T.Yang; S.A.Simon

    2004-01-01

    AIM : One of the primary mechanisms by which neurons regulate their excitability is through of ion channel phosphorylafion. Compounds that increase noeiceptor excitability can cause hyporalgesia or allodynia whereas compounds that decrease noeiceptor excitability can be used as analgesics to relieve pain arising from inflammation or trauma. METHODS:

  1. PROTEIN KINASES AND CENTRAL SENSITIZATION OF SPINAL DORSAL HORN NEURONS:CENTRAL MECHANISMS OF PAIN

    Institute of Scientific and Technical Information of China (English)

    QING LIN

    2003-01-01

    @@ The enhanced responsiveness of spinal dorsal horn neurons, including spinothalamic tract (STT) cells, that follows peripheral tissue injury or inflammation is thought to underlie the development of secondary hyperalgesia and allodynia and is referred to as "central sensitization" because the increases in excitability do not appear to depend on continued activity of peripheral nociceptors.

  2. Speciifc effects of c-Jun NH2-terminal kinase-interacting protein 1 in neuronal axons

    Institute of Scientific and Technical Information of China (English)

    Shu Tang; Qiang Wen; Xiao-jian Zhang; Quan-cheng Kan

    2016-01-01

    c-Jun NH2-terminal kinase (JNK)-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B (TrkB) anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of TrkB anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neuronsin vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed TrkB com-plexesin vitro andin vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of TrkB gradually increased in axon terminals. However, the distribution of TrkB reduced in axon terminals after knocking out JNK-interact-ing protein 1. In addition, there were differences in distribution of TrkB after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of TrkB in dendrites. These ifndings conifrm that JNK-inter-acting protein 1 can interact with TrkB in neuronal cells, and can regulate the transport of TrkB in axons, but not in dendrites.

  3. Novel mechanism for gonadotropin-releasing hormone neuronal migration involving Gas6/Ark signaling to p38 mitogen-activated protein kinase.

    Science.gov (United States)

    Allen, Melissa P; Linseman, Daniel A; Udo, Hiroshi; Xu, Mei; Schaack, Jerome B; Varnum, Brian; Kandel, Eric R; Heidenreich, Kim A; Wierman, Margaret E

    2002-01-01

    Gonadotropin-releasing hormone (GnRH) is the central regulator of the reproductive axis. Normal sexual maturation depends on the migration of GnRH neurons from the olfactory placode to the hypothalamus during development. Previously, we showed restricted expression of the membrane receptor adhesion-related kinase (Ark) in immortalized cell lines derived from migratory but not postmigratory GnRH neurons. In addition, Ark and GnRH transcripts were detected along the GnRH neuron migratory route in the E13 mouse cribriform plate. In the present study, we examined the role of Ark and its ligand, Gas6 (encoded by growth arrest-specific gene 6), in GnRH neuron migration. Gas6 stimulated lamellipodial extension, membrane ruffling, and chemotaxis of immortalized NLT GnRH neuronal cells via the Ark receptor. Gas6/Ark signaling promoted activation of the Rho family GTPase Rac, and adenoviral-mediated expression of dominant negative N17Rac abolished Gas6/Ark-induced actin cytoskeletal reorganization and migration of GnRH neuronal cells. In addition, p38 MAPK was activated downstream of Ark and Rac, and inhibition of p38 MAPK with either SB203580 or adenoviral dominant negative p38alpha also blocked Gas6/Ark-mediated migration. Finally, downstream of Rac and p38 mitogen-activated protein kinase (MAPK), Gas6/Ark signaling promoted activation of MAPK-activated protein kinase 2 and induced phosphorylation of HSP25, a known regulator of cortical actin remodeling. The data are the first to demonstrate a migratory signaling pathway downstream of Ark/Axl family receptors and suggest a previously unidentified role for p38 MAPK in neuronal migration. Furthermore, these studies support a potential role for Ark in the regulation of GnRH neuronal migration.

  4. Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway

    Institute of Scientific and Technical Information of China (English)

    Sun ZHANG; Ying HUANG; Yi-chun ZHU; Tai YAO

    2005-01-01

    Aim: To investigate the mechanism of the action of estrogen, which stimulates the release of secreted amyloid precursor protein α (sAPPα) and decreases the gen eration of amyloid-β protein (Aβ), a dominant component in senile plaques in the brains of Alzheimer's disease patients. Methods: Experiments were carried out inprimary rat cortical neurons, and Western blot was used to detect sAPPα in aculture medium and the total amount of cellular amyloid precursor protein (APP) in neurons. Results: 17β-Estradiol (but not 17α-estradiol) and β-estradiol 6-(Ocarboxymethyl) oxime: BSA increased the secretion of sAPPα and this effect was blocked by protein kinase C (PKC) inhibitor calphostin C, but not by the classical estrogen receptor antagonist ICI 182,780. Meanwhile, 17β-estradiol did not alter the synthesis of cellular APP. Conclusion: The effect of 17β-estradiol on sAPPα secretion is likely mediated through the membrane binding sites, and needs molecular configuration specificity of the ligand. Furthermore, the action of the PKC dependent pathway might be involved in estrogen-induced sAPPα secretion.

  5. Gabapentin Inhibits Protein Kinase C Epsilon Translocation in Cultured Sensory Neurons with Additive Effects When Coapplied with Paracetamol (Acetaminophen

    Directory of Open Access Journals (Sweden)

    Vittorio Vellani

    2017-01-01

    Full Text Available Gabapentin is a well-established anticonvulsant drug which is also effective for the treatment of neuropathic pain. Although the exact mechanism leading to relief of allodynia and hyperalgesia caused by neuropathy is not known, the blocking effect of gabapentin on voltage-dependent calcium channels has been proposed to be involved. In order to further evaluate its analgesic mechanisms, we tested the efficacy of gabapentin on protein kinase C epsilon (PKCε translocation in cultured peripheral neurons isolated from rat dorsal root ganglia (DRGs. We found that gabapentin significantly reduced PKCε translocation induced by the pronociceptive peptides bradykinin and prokineticin 2, involved in both inflammatory and chronic pain. We recently showed that paracetamol (acetaminophen, a very commonly used analgesic drug, also produces inhibition of PKCε. We tested the effect of the combined use of paracetamol and gabapentin, and we found that the inhibition of translocation adds up. Our study provides a novel mechanism of action for gabapentin in sensory neurons and suggests a mechanism of action for the combined use of paracetamol and gabapentin, which has recently been shown to be effective, with a cumulative behavior, in the control of postoperative pain in human patients.

  6. Gabapentin Inhibits Protein Kinase C Epsilon Translocation in Cultured Sensory Neurons with Additive Effects When Coapplied with Paracetamol (Acetaminophen)

    Science.gov (United States)

    2017-01-01

    Gabapentin is a well-established anticonvulsant drug which is also effective for the treatment of neuropathic pain. Although the exact mechanism leading to relief of allodynia and hyperalgesia caused by neuropathy is not known, the blocking effect of gabapentin on voltage-dependent calcium channels has been proposed to be involved. In order to further evaluate its analgesic mechanisms, we tested the efficacy of gabapentin on protein kinase C epsilon (PKCε) translocation in cultured peripheral neurons isolated from rat dorsal root ganglia (DRGs). We found that gabapentin significantly reduced PKCε translocation induced by the pronociceptive peptides bradykinin and prokineticin 2, involved in both inflammatory and chronic pain. We recently showed that paracetamol (acetaminophen), a very commonly used analgesic drug, also produces inhibition of PKCε. We tested the effect of the combined use of paracetamol and gabapentin, and we found that the inhibition of translocation adds up. Our study provides a novel mechanism of action for gabapentin in sensory neurons and suggests a mechanism of action for the combined use of paracetamol and gabapentin, which has recently been shown to be effective, with a cumulative behavior, in the control of postoperative pain in human patients.

  7. Essentials of creatine in sports and health

    National Research Council Canada - National Science Library

    Stout, Jeffrey R; Kalman, Douglas; Antonio, Jose

    2008-01-01

    ... and NIH databases. With all of the misinformation regarding the effects of creatine supplementation on health and sports performance, Essentials of Creatine in Sports and Health brings together the information on how creatine affecs body composition, exercise performance, and health. Supported by the International Society of Sports Nutrition, this...

  8. Determination of sperm creatine kinase and its isozyme in infertile patients%不育症患者精子肌酸激酶活性及其同工酶测定

    Institute of Scientific and Technical Information of China (English)

    罗比; 陈建; 漆著

    2006-01-01

    BACKGROUND: As a biochemical marker of cytoplasm, the increased activity of creatine kinase (CK) in human spermatozoa is correlated with both the residual cytoplasma and the ratio of sperm with abnormal func tion. It is a marker of mature sperm and associated with the potential of in semination. OBJECTIVE: To investigate the differences of CK activity in sperm and the relative contents of sperm CK-MM and CK-BB isoenzymes between normal fertile males and infertile males, and evaluate its significance in clinical diagnosis of male infertility. DESIGN: Case-control observation. SETTING: Laboratory of Biochemistry, Family Planning Research Insti tute of Sichuan Province. PARTICIPANTS: Ninety-four male infertile patients between January 1999 and October 2000 were selected from the Department of Family Planning Sciences of Sichuan Province, who had no aspermatism with their wives proved to be fertile. The average age of subjects were 31 years. Eighty subjects with the sperm count > 2×1010 L-1 were taken as normal sperm group and 14 subjects with the sperm counts < 2×1010 L-1 were considered as oligospermia group. Semen obtained from 27 healthy males who were normal in routine examinations and with children was taken as the healthy control group.METHODS: Semen sample collected by masturbation after abstinence of 3 to 5 days was incubated at 37 ℃ for liquefication and routinely analyzed.Total activity of CK in sperm was determined by using a kinetic spectrophotometry and the relative contents of CK isozyme was determined by agarose gel electrophoresis followed by density scanning of CK isozyme.MAIN OUTCOME MEASURES: Sperm counts, percentages of viability and motility of sperm, total CK activity and the relative contents of CK-MM and CK-BB isozyme in spermatozoa.RESULTS: A total of 94 enrolled patients and 27 normal controls were involved in the analysis of results. ①Sperm counts, percentage of viability and motility in oligospermia group ( Ⅱ + Ⅲ, WHO method

  9. Specific serine-proline phosphorylation and glycogen synthase kinase 3β-directed subcellular targeting of stathmin 3/Sclip in neurons.

    Science.gov (United States)

    Devaux, Sara; Poulain, Fabienne E; Devignot, Véronique; Lachkar, Sylvie; Irinopoulou, Theano; Sobel, André

    2012-06-22

    During nervous system development, neuronal growth, migration, and functional morphogenesis rely on the appropriate control of the subcellular cytoskeleton including microtubule dynamics. Stathmin family proteins play major roles during the various stages of neuronal differentiation, including axonal growth and branching, or dendritic development. We have shown previously that stathmins 2 (SCG10) and 3 (SCLIP) fulfill distinct, independent and complementary regulatory roles in axonal morphogenesis. Although the two proteins have been proposed to display the four conserved phosphorylation sites originally identified in stathmin 1, we show here that they possess distinct phosphorylation sites within their specific proline-rich domains (PRDs) that are differentially regulated by phosphorylation by proline-directed kinases involved in the control of neuronal differentiation. ERK2 or CDK5 phosphorylate the two proteins but with different site specificities. We also show for the first time that, unlike stathmin 2, stathmin 3 is a substrate for glycogen synthase kinase (GSK) 3β both in vitro and in vivo. Interestingly, stathmin 3 phosphorylated at its GSK-3β target site displays a specific subcellular localization at neuritic tips and within the actin-rich peripheral zone of the growth cone of differentiating hippocampal neurons in culture. Finally, pharmacological inhibition of GSK-3β induces a redistribution of stathmin 3, but not stathmin 2, from the periphery toward the Golgi region of neurons. Stathmin proteins can thus be either regulated locally or locally targeted by specific phosphorylation, each phosphoprotein of the stathmin family fulfilling distinct and specific roles in the control of neuronal differentiation.

  10. The I2020T Leucine-rich repeat kinase 2 transgenic mouse exhibits impaired locomotive ability accompanied by dopaminergic neuron abnormalities

    Directory of Open Access Journals (Sweden)

    Maekawa Tatsunori

    2012-04-01

    Full Text Available Abstract Background Leucine-rich repeat kinase 2 (LRRK2 is the gene responsible for autosomal-dominant Parkinson’s disease (PD, PARK8, but the mechanism by which LRRK2 mutations cause neuronal dysfunction remains unknown. In the present study, we investigated for the first time a transgenic (TG mouse strain expressing human LRRK2 with an I2020T mutation in the kinase domain, which had been detected in the patients of the original PARK8 family. Results The TG mouse expressed I2020T LRRK2 in dopaminergic (DA neurons of the substantia nigra, ventral tegmental area, and olfactory bulb. In both the beam test and rotarod test, the TG mice exhibited impaired locomotive ability in comparison with their non-transgenic (NTG littermates. Although there was no obvious loss of DA neurons in either the substantia nigra or striatum, the TG brain showed several neurological abnormalities such as a reduced striatal dopamine content, fragmentation of the Golgi apparatus in DA neurons, and an increased degree of microtubule polymerization. Furthermore, the tyrosine hydroxylase-positive primary neurons derived from the TG mouse showed an increased frequency of apoptosis and had neurites with fewer branches and decreased outgrowth in comparison with those derived from the NTG controls. Conclusions The I2020T LRRK2 TG mouse exhibited impaired locomotive ability accompanied by several dopaminergic neuron abnormalities. The TG mouse should provide valuable clues to the etiology of PD caused by the LRRK2 mutation.

  11. The calmodulin-dependent protein kinase II inhibitor KN-93 protects rat cerebral cortical neurons from N-methyl-D-aspartic acid-induced injury

    Institute of Scientific and Technical Information of China (English)

    Xuewen Liu; Cui Ma; Ruixian Xing; Weiwei Zhang; Buxian Tian; Xidong Li; Qiushi Li; Yanhui Zhang

    2013-01-01

    In this study, primary cultured cerebral cortical neurons of Sprague-Dawley neonatal rats were treated with 0.25, 0.5, and 1.0 μM calmodulin-dependent protein kinase II inhibitor KN-93 after 50 μM N-methyl-D-aspartic acid-induced injury. Results showed that, compared with N-methyl-Daspartic acid-induced injury neurons, the activity of cells markedly increased, apoptosis was significantly reduced, leakage of lactate dehydrogenase decreased, and intracellular Ca2+ concentrations in neurons reduced after KN-93 treatment. The expression of caspase-3, phosphorylated calmodulin-dependent protein kinase II and total calmodulin-dependent protein kinase II protein decreased after KN-93 treatment. And the effect was apparent at a dose of 1.0 μM KN-93. Experimental findings suggest that KN-93 can induce a dose-dependent neuroprotective effect, and that the underlying mechanism may be related to the down-regulation of caspase-3 and calmodulin- dependent protein kinase II expression.

  12. Prognostic implications of myocardial creatine kinase and cardiac troponin in coronary artery bypass surgery Implicação prognóstica da creatino-quinase miocárdica e troponina na revascularização do miocárdio

    Directory of Open Access Journals (Sweden)

    Fábio P. Taniguchi

    2003-09-01

    Full Text Available OBJECTIVES: To evaluate the prognostic implications of myocardial creatine kinase and troponin I (cTn I in blood samples from the coronary sinus of patients submitted to coronary artery bypass surgery both with and without ischemic preconditioning. METHODS: From October 1998 to May 1999, 35 patients with coronary artery disease who were submitted to coronary artery bypass surgery were studied. Samples containing creatine kinase and cTn I were obtained from the great cardiac vein during surgery at the onset of cardiopulmonary bypass, at the end of the first anastomosis, and at the end of cardiopulmonary bypass. In May 2002, 29 patients were evaluated in regards to the angina functional class, congestive heart failure, number of hospitalizations, myocardial infarction and death. There were 15 patients in the Preconditioned group and 14 in the Control group. Each group was subdivided into patients with and without cardiovascular symptoms. RESULTS: The Control and Preconditioned groups were not significantly different in relation to frequency of cardiovascular symptoms. There were progressive increases of the creatine kinase and cTn I levels at different Interval s of the study. The cTn I in the Preconditioned group was 1.21 ± 0.64 ng/mL and 3.19 ± 3.21 ng/mL in the Control group (pOBJETIVO: Avaliar a implicação prognóstica da dosagem da creatino-quinase miocárdica (CKMB e Troponina I (cTn I em amostras no seio coronariano, na evolução de pacientes submetidos a revascularização do miocárdio (RM, com e sem o pré-condicionamento isquêmico. MÉTODO: Entre outubro de 1998 e maio de 1999, 35 pacientes com insuficiência coronariana foram submetidos a RM foram estudados. No intra-operatório foram coletadas amostras do seio coronariano para dosagem de CKMB e cTn I. Os momentos de coleta foram: momento 1-no início da circulação extracorpórea (CEC, momento 2- após a primeira anastomose e momento 3- no final da CEC. Em maio de 2002, 29

  13. REVERSE SIGNALING BY GPI-LINKED MANDUCA EPHRIN REQUIRES A SRC FAMILY KINASE TO RESTRICT NEURONAL MIGRATION IN VIVO

    Science.gov (United States)

    Coate, Thomas M.; Swanson, Tracy L.; Copenhaver, Philip F.

    2011-01-01

    Reverse signaling via GPI-linked Ephrins may help control cell proliferation and outgrowth within the nervous system, but the mechanisms underlying this process remain poorly understood. In the embryonic enteric nervous system (ENS) of the moth Manduca sexta, migratory neurons forming the enteric plexus (EP cells) express a single Ephrin ligand (GPI-linked MsEphrin), while adjacent midline cells that are inhibitory to migration express the cognate receptor (MsEph). Knocking down MsEph receptor expression in cultured embryos with antisense morpholino oligonucleotides allowed the EP cells to cross the midline inappropriately, consistent with the model that reverse signaling via MsEphrin mediates a repulsive response in the ENS. Src family kinases have been implicated in reverse signaling by type-A Ephrins in other contexts, and MsEphrin colocalizes with activated forms of endogenous Src in the leading processes of the EP cells. Pharmacological inhibition of Src within the developing ENS induced aberrant midline crossovers, similar to the effect of blocking MsEphrin reverse signaling. Hyperstimulating MsEphrin reverse signaling with MsEph-Fc fusion proteins induced the rapid activation of endogenous Src specifically within the EP cells, as assayed by Western blots of single embryonic gut explants and by whole-mount immunostaining of cultured embryos. In longer cultures, treatment with MsEph-Fc caused a global inhibition of EP cell migration and outgrowth, an effect that was prevented by inhibiting Src activation. These results support the model that MsEphrin reverse signaling induces the Src-dependent retraction of EP cell processes away from the enteric midline, thereby helping to confine the neurons to their appropriate pathways. PMID:19295147

  14. Cyclin-dependent kinase 5 regulates PSD-95 ubiquitination in neurons.

    Science.gov (United States)

    Bianchetta, Michael J; Lam, TuKiet T; Jones, Stephen N; Morabito, Maria A

    2011-08-17

    Cyclin-dependent kinase 5 (Cdk5) and its activator p35 have been implicated in drug addiction, neurodegenerative diseases such as Alzheimer's, learning and memory, and synapse maturation and plasticity. However, the molecular mechanisms by which Cdk5 regulates synaptic plasticity are still unclear. PSD-95 is a major postsynaptic scaffolding protein of glutamatergic synapses that regulates synaptic strength and plasticity. PSD-95 is ubiquitinated by the ubiquitin E3 ligase Mdm2, and rapid and transient PSD-95 ubiquitination has been implicated in NMDA receptor-induced AMPA receptor endocytosis. Here we demonstrate that genetic or pharmacological reduction of Cdk5 activity increases the interaction of Mdm2 with PSD-95 and enhances PSD-95 ubiquitination without affecting PSD-95 protein levels in vivo in mice, suggesting a nonproteolytic function of ubiquitinated PSD-95 at synapses. We show that PSD-95 ubiquitination correlates with increased interaction with β-adaptin, a subunit of the clathrin adaptor protein complex AP-2. This interaction is increased by genetic reduction of Cdk5 activity or NMDA receptor stimulation and is dependent on Mdm2. Together these results support a function for Cdk5 in regulating PSD-95 ubiquitination and its interaction with AP-2 and suggest a mechanism by which PSD-95 may regulate NMDA receptor-induced AMPA receptor endocytosis.

  15. Relation of Post-Coronary Artery Bypass Graft Creatine Kinase-MB Elevations and New Q Waves With Long-Term Cardiovascular Death in Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease.

    Science.gov (United States)

    Domanski, Michael; Farkouh, Michael E; Zak, Victor; French, John; Alexander, John H; Bochenek, Andrzej; Hamon, Martial; Mahaffey, Kenneth; Puskas, John; Smith, Peter; Shrader, Peter; Fuster, Valentin

    2016-12-01

    Associations of early creatine phosphokinase-MB (CK-MB) elevation and new Q waves and their association with cardiovascular death (CVD) after coronary artery bypass grafting (CABG) have been reported, but this association has not been studied in a large population of patients with diabetes mellitus. In this study, we examine the association of periprocedural CK-MB elevations and new Q waves with CVD in the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease trial. Cox proportional hazards regression was used to assess the relation of CK-MB elevations and new Q waves in the first 24 hours after procedure and their relation to CVD; logistic regression was used to assess odds ratios of these variables. Hazard ratios, 95% confidence intervals, and p values associated with Wald chi-square test are reported. CK-MB elevation in first 24 hours after procedure was independently associated with CVD. CVD hazard increased by 6% (p URL); odds of new post-CABG Q waves increased by a factor of 1.08 (p URL, HR was >2. CK-MB URL multiples of 7, 12, and 15 were associated with new Q-wave odds ratios of 9, 16, and 27 times, respectively (p ≤0.001, C-statistic >0.70). New Q waves were independently associated with survival in the multivariate model only when CK-MB was excluded (p = 0.01). In conclusion, independent associations included (1) CVD and early post-CABG CK-MB elevation; (2) new Q waves with early post-CABG CK-MB elevation; (3) CVD with new Q waves only when CK-MB elevation is excluded from analysis.

  16. Environmental neurotoxic pesticide dieldrin activates a non receptor tyrosine kinase to promote PKCδ-mediated dopaminergic apoptosis in a dopaminergic neuronal cell model.

    Science.gov (United States)

    Saminathan, Hariharan; Asaithambi, Arunkumar; Anantharam, Vellareddy; Kanthasamy, Anumantha G; Kanthasamy, Arthi

    2011-10-01

    Oxidative stress and apoptosis are two key pathophysiological mechanisms underlying dopaminergic degeneration in Parkinson's disease (PD). Recently, we identified that proteolytic activation of protein kinase C-delta (PKCδ), a member of the novel PKC family, contributes to oxidative stress-induced dopaminergic degeneration and that phosphorylation of tyrosine residue 311 (tyr311) on PKCδ is a key event preceding the PKCδ proteolytic activation during oxidative damage. Herein, we report that a non-receptor tyrosine kinase Fyn is significantly expressed in a dopaminergic neuronal N27 cell model. Exposure of N27 cells to the dopaminergic toxicant dieldrin (60 μM) rapidly activated Fyn kinase, PKCδ-tyr311 phosphorylation and proteolytic cleavage. Fyn kinase activation precedes the caspase-3-mediated proteolytic activation of PKCδ. Pre-treatment with p60-tyrosine-specific kinase inhibitor (TSKI) almost completely attenuated dieldrin-induced phosphorylation of PKCδ-tyr311 and its proteolytic activation. Additionally, TSKI almost completely blocked dieldrin-induced apoptotic cell death. To further confirm Fyn's role in the pro-apoptotic function of PKCδ, we adopted the RNAi approach. siRNA-mediated knockdown of Fyn kinase also effectively attenuated dieldrin-induced phosphorylation of PKCδ-tyr311, caspase-3-mediated PKCδ proteolytic cleavage, and DNA fragmentation, suggesting that Fyn kinase regulates the pro-apoptotic function of PKCδ. Collectively, these results demonstrate for the first time that Fyn kinase is a pro-apoptotic kinase that regulates upstream signaling of the PKCδ-mediated apoptotic cell death pathway in neurotoxicity models of pesticide exposure. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Retinoic acids acting through retinoid receptors protect hippocampal neurons from oxygen-glucose deprivation-mediated cell death by inhibition of c-jun-N-terminal kinase and p38 mitogen-activated protein kinase.

    Science.gov (United States)

    Shinozaki, Y; Sato, Y; Koizumi, S; Ohno, Y; Nagao, T; Inoue, K

    2007-06-15

    Retinoic acids (RAs), including all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA), play fundamental roles in a variety of physiological events in vertebrates, through their specific nuclear receptors: retinoic acid receptor (RAR) and retinoid X receptor (RXR). Despite the physiological importance of RA, their functional significance under pathological conditions is not well understood. We examined the effect of ATRA on oxygen/glucose-deprivation/reperfusion (OGD/Rep)-induced neuronal damage in cultured rat hippocampal slices, and found that ATRA significantly reduced neuronal death. The cytoprotective effect of ATRA was observed not only in cornu ammonis (CA) 1 but also in CA2 and dentate gyrus (DG), and was attenuated by selective antagonists for RAR or RXR. By contrast, in the CA3 region, no protective effects of ATRA were observed. The OGD/Rep also increased phosphorylated forms of c-jun-N-terminal kinase (P-JNK) and p38 (P-p38) in hippocampus, and specific inhibitors for these kinases protected neurons. ATRA prevented the increases in P-JNK and P-p38 after OGD/Rep, as well as the decrease in NeuN and its shrinkage, all of which were inhibited by antagonists for RAR or RXR. These findings suggest that the ATRA signaling via retinoid receptors results in the inhibition of JNK and p38 activation, leading to the protection of neurons against OGD/Rep-induced damage in the rat hippocampus.

  18. Insufficient Astrocyte-Derived Brain-Derived Neurotrophic Factor Contributes to Propofol-Induced Neuron Death Through Akt/Glycogen Synthase Kinase 3β/Mitochondrial Fission Pathway.

    Science.gov (United States)

    Liu, Yanan; Yan, Yasheng; Inagaki, Yasuyoshi; Logan, Sarah; Bosnjak, Zeljko J; Bai, Xiaowen

    2017-07-01

    Growing animal evidence demonstrates that prolonged exposure to propofol during brain development induces widespread neuronal cell death, but there is little information on the role of astrocytes. Astrocytes can release neurotrophic growth factors such as brain-derived neurotrophic factor (BDNF), which can exert the protective effect on neurons in paracrine fashion. We hypothesize that during propofol anesthesia, BDNF released from developing astrocytes may not be sufficient to prevent propofol-induced neurotoxicity. Hippocampal astrocytes and neurons isolated from neonatal Sprague Dawley rats were exposed to propofol at a clinically relevant dose of 30 μM or dimethyl sulfoxide as control for 6 hours. Propofol-induced cell death was determined by propidium iodide (PI) staining in astrocyte-alone cultures, neuron-alone cultures, or cocultures containing either low or high density of astrocytes (1:9 or 1:1 ratio of astrocytes to neurons ratio [ANR], respectively). The astrocyte-conditioned medium was collected 12 hours after propofol exposure and measured by protein array assay. BDNF concentration in astrocyte-conditioned medium was quantified using enzyme-linked immunosorbent assay. Neuron-alone cultures were treated with BDNF, tyrosine receptor kinase B inhibitor cyclotraxin-B, glycogen synthase kinase 3β (GSK3β) inhibitor CHIR99021, or mitochondrial fission inhibitor Mdivi-1 before propofol exposure. Western blot was performed for quantification of the level of protein kinase B and GSK3β. Mitochondrial shape was visualized through translocase of the outer membrane 20 staining. Propofol increased cell death in neurons by 1.8-fold (% of PI-positive cells [PI%] = 18.6; 95% confidence interval [CI], 15.2-21.9, P .05]). Astrocytes secreted BDNF in a cell density-dependent way and propofol decreased BDNF secretion from astrocytes. Administration of BDNF, CHIR99021, or Mdivi-1 significantly attenuated the propofol-induced neuronal death and aberrant mitochondria in

  19. Determinação das atividades séricas de creatina quinase, lactato desidrogenase e aspartato aminotransferase em eqüinos de diferentes categorias de atividade Determination of serum activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase in horses of different activities classes

    Directory of Open Access Journals (Sweden)

    I.A. Câmara e Silva

    2007-02-01

    Full Text Available The creatine kinase (CK, lactate dehydrogenase (LDH, and aspartate aminotransferase (AST seric activities in horses of different activity classes (athlete, traction, and reproduction, were compared. Fifty-eight horses were alloted into three groups - group 1 with 20 athletes, "vaquejada" competitors; group 2 with 20 breeding horses; and group 3 with 18 draft horses, averaging 10 working hours daily. The average values for CK serum activity were 80.2, 83.9, and 94.4 U/l in groups 1, 2, and 3, respectively. Result of group 3 was significantly different from the other groups. The averages values for LDH were 102.5, 98.6, and 112.8 U/l in groups 1, 2, and 3, respectively, with no statistical difference between groups. The AST averages were 56.8, 33.0, and 50.1 U/l in groups 1, 2, and 3, respectively, with group 2 significantly differing from the others. Clinical biochemistry values of muscular function in horses varied according to activity category.

  20. Concentrações de creatino quinase, aspartato aminotransferase e desidrogenase lática em potros do nascimento até os seis meses de idade Concentration of creatine kinase, aspartate aminotransferase and lactate dehydrogenase in foals from birth up to sixth month

    Directory of Open Access Journals (Sweden)

    Elisiane Lourdes Da Cás

    2001-12-01

    Full Text Available Dez potros da raça Puro Sangue de Corrida (PSC, de ambos os sexos, foram avaliados quanto à concentração das enzimas séricas creatino quinase (CK, aspartato aminotransferase (AST e deshidrogenase lática (DHL. Foram colhidas amostras sangüíneas diariamente do 1º ao 7ºdia de vida e depois aos 15, 30, 60, 90, 120, 150 e 180 dias de idade. A concentração da CK mostrou um decréscimo significativo (pTen Thoroughbred foals, male and female, had the seric concentration of creatine kinase (CK, aspartate aminotransferase (AST and lactate dehydrogenase (LDH determined. Blood samples were collected every day from days 1 to 7 and on days 15, 30, 60, 90, 120, 150 and 180 of age. CK activity decreased significantly (p< 0.0003 in the first week and showed significant variation between day 15 and 6 months of age. AST showed a significant (p< 0.0001 increase in its values until 102 days of age, decreasing subsequently until 6 months of age. LDH values decreased significantly (p< 0.0002 between days 15 and 120, increasing subsequently until 6 months of age. At 6 months of age CK, AST and LDH activities were close to those of adult horses.

  1. The Neuron-Specific Rai (ShcC) Adaptor Protein Inhibits Apoptosis by Coupling Ret to the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway

    Science.gov (United States)

    Pelicci, Giuliana; Troglio, Flavia; Bodini, Alessandra; Melillo, Rosa Marina; Pettirossi, Valentina; Coda, Laura; De Giuseppe, Antonio; Santoro, Massimo; Pelicci, Pier Giuseppe

    2002-01-01

    Rai is a recently identified member of the family of Shc-like proteins, which are cytoplasmic signal transducers characterized by the unique PTB-CH1-SH2 modular organization. Rai expression is restricted to neuronal cells and regulates in vivo the number of postmitotic sympathetic neurons. We report here that Rai is not a common substrate of receptor tyrosine kinases under physiological conditions and that among the analyzed receptors (Ret, epidermal growth factor receptor, and TrkA) it is activated specifically by Ret. Overexpression of Rai in neuronal cell lines promoted survival by reducing apoptosis both under conditions of limited availability of the Ret ligand glial cell line-derived neurotrophic factor (GDNF) and in the absence of Ret activation. Overexpressed Rai resulted in the potentiation of the Ret-dependent activation of phosphatidylinositol 3-kinase (PI3K) and Akt. Notably, increased Akt phosphorylation and PI3K activity were also found under basal conditions, e.g., in serum-starved neuronal cells. Phosphorylated and hypophosphorylated Rai proteins form a constitutive complex with the p85 subunit of PI3K: upon Ret triggering, the Rai-PI3K complex is recruited to the tyrosine-phosphorylated Ret receptor through the binding of the Rai PTB domain to tyrosine 1062 of Ret. In neurons treated with low concentrations of GDNF, the prosurvival effect of Rai depends on Rai phosphorylation and Ret activation. In the absence of Ret activation, the prosurvival effect of Rai is, instead, phosphorylation independent. Finally, we showed that overexpression of Rai, at variance with Shc, had no effects on the early peak of mitogen-activated protein kinase (MAPK) activation, whereas it increased its activation at later time points. Phosphorylated Rai, however, was not found in complexes with Grb2. We propose that Rai potentiates the MAPK and PI3K signaling pathways and regulates Ret-dependent and -independent survival signals. PMID:12242309

  2. Orexin A Inhibits Propofol-Induced Neurite Retraction by a Phospholipase D/Protein Kinase Cε-Dependent Mechanism in Neurons

    Science.gov (United States)

    Björnström, Karin; Turina, Dean; Strid, Tobias; Sundqvist, Tommy; Eintrei, Christina

    2014-01-01

    Background The intravenous anaesthetic propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons. Orexin A (OA) is an endogenous neuropeptide regulating wakefulness and may counterbalance anaesthesia. We aim to investigate if OA interacts with anaesthetics by inhibition of the propofol-induced neurite retraction. Methods In primary cortical cell cultures from newborn rats’ brains, live cell light microscopy was used to measure neurite retraction after propofol (2 µM) treatment with or without OA (10 nM) application. The intracellular signalling involved was tested using a protein kinase C (PKC) activator [phorbol 12-myristate 13-acetate (PMA)] and inhibitors of Rho-kinase (HA-1077), phospholipase D (PLD) [5-fluoro-2-indolyl des-chlorohalopemide (FIPI)], PKC (staurosporine), and a PKCε translocation inhibitor peptide. Changes in PKCε Ser729 phosphorylation were detected with Western blot. Results The neurite retraction induced by propofol is blocked by Rho-kinase and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, staurosporine and PKCε translocation inhibitor peptide. OA increases via PLD and propofol decreases PKCε Ser729 phosphorylation, a crucial step in the activation of PKCε. Conclusions Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC inhibits neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD/PKCε-mediated pathway, and PKCε maybe the key enzyme where the wakefulness and anaesthesia signal pathways converge. PMID:24828410

  3. Src Family Kinase Inhibitors Antagonize the Toxicity of Multiple Serotypes of Botulinum Neurotoxin in Human Embryonic Stem Cell-Derived Motor Neurons

    Science.gov (United States)

    Burnett, James C.; Nuss, Jonathan E.; Wanner, Laura M.; Peyser, Brian D.; Du, Hao T.; Gomba, Glenn Y.; Kota, Krishna P.; Panchal, Rekha G.; Gussio, Rick; Kane, Christopher D.; Tessarollo, Lino

    2015-01-01

    Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of BoNT intoxication in human motor neurons, focusing on Src family kinase (SFK) signaling. Motor neurons derived from human embryonic stem (hES) cells were treated with a panel of SFK inhibitors and intoxicated with BoNT serotypes A, B, or E (which are responsible for >95 % of human botulism cases). Subsequently, it was found that bosutinib, dasatinib, KX2-391, PP1, PP2, Src inhibitor-1, and SU6656 significantly antagonized all three of the serotypes. Furthermore, the data indicated that the treatment of hES-derived motor neurons with multiple SFK inhibitors increased the antagonistic effect synergistically. Mechanistically, the small molecules appear to inhibit BoNTs by targeting host pathways necessary for intoxication and not by directly inhibiting the toxins’ proteolytic activity. Importantly, the identified inhibitors are all well-studied with some in clinical trials while others are FDA-approved drugs. Overall, this study emphasizes the importance of targeting host neuronal pathways, rather than the toxin’s enzymatic components, to antagonize multiple BoNT serotypes in motor neurons. PMID:25782580

  4. Fyn Kinase regulates GluN2B subunit-dominant NMDA receptors in human induced pluripotent stem cell-derived neurons.

    Science.gov (United States)

    Zhang, Wen-Bo; Ross, P Joel; Tu, YuShan; Wang, Yongqian; Beggs, Simon; Sengar, Ameet S; Ellis, James; Salter, Michael W

    2016-04-04

    NMDA receptor (NMDAR)-mediated fast excitatory neurotransmission is implicated in a broad range of physiological and pathological processes in the mammalian central nervous system. The function and regulation of NMDARs have been extensively studied in neurons from rodents and other non-human species, and in recombinant expression systems. Here, we investigated human NMDARs in situ by using neurons produced by directed differentiation of human induced pluripotent stem cells (iPSCs). The resultant cells showed electrophysiological characteristics demonstrating that they are bona fide neurons. In particular, human iPSC-derived neurons expressed functional ligand-gated ion channels, including NMDARs, AMPA receptors, GABAA receptors, as well as glycine receptors. Pharmacological and electrophysiological properties of NMDAR-mediated currents indicated that these were dominated by receptors containing GluN2B subunits. The NMDAR currents were suppressed by genistein, a broad-spectrum tyrosine kinase inhibitor. The NMDAR currents were also inhibited by a Fyn-interfering peptide, Fyn(39-57), but not a Src-interfering peptide, Src(40-58). Together, these findings are the first evidence that tyrosine phosphorylation regulates the function of NMDARs in human iPSC-derived neurons. Our findings provide a basis for utilizing human iPSC-derived neurons in screening for drugs targeting NMDARs in neurological disorders.

  5. Neuropilin 2 Signaling Is Involved in Cell Positioning of Adult-born Neurons through Glycogen Synthase Kinase-3β (GSK3β).

    Science.gov (United States)

    Ng, Teclise; Hor, Catherine H H; Chew, Benjamin; Zhao, Jing; Zhong, Zhong; Ryu, Jae Ryun; Goh, Eyleen L K

    2016-11-25

    Proper positioning of neurons is fundamental for brain functions. However, little is known on how adult-born neurons generated in the hilar side of hippocampal dentate gyrus migrate into the granular cell layer. Because class 3 Semaphorins (Sema3) are involved in dendritic growth of these newborn neurons, we examined whether they are essential for cell positioning. We disrupted Sema3 signaling by silencing neuropilin 1 (NRP1) or 2 (NRP2), the main receptors for Sema3A and Sema3F, in neural progenitors of adult mouse dentate gyrus. Silencing of NRP2, but not NRP1, affected cell positioning of adult newborn neurons. Glycogen synthase kinase-3β (GSK3β) knockdown phenocopied this NRP2 silencing-mediated cell positioning defect, but did not affect dendritic growth. Furthermore, GSK3β is activated upon stimulation with Sema3F, and GSK3β overexpression rescued the cell positioning phenotypes seen in NRP2-deficient neurons. These results point to a new role for NRP2 in the positioning of neurons during adult hippocampal neurogenesis, acting via the GSK3β signaling pathway. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Creatine

    Science.gov (United States)

    ... weeks enhances the effects of the antidepressant drug escitalopram in women with major depressive disorder. Diabetes. Early ... not seem to improve aerobic exercise capacity, pain, sleep, quality of life, or mental function in people ...

  7. The tyrosine kinase receptor Tyro3 enhances lifespan and neuropeptide Y (Npy) neuron survival in the mouse anorexia (anx) mutation.

    Science.gov (United States)

    Kim, Dennis Y; Yu, Joanna; Mui, Ryan K; Niibori, Rieko; Taufique, Hamza Bin; Aslam, Rukhsana; Semple, John W; Cordes, Sabine P

    2017-05-01

    Severe appetite and weight loss define the eating disorder anorexia nervosa, and can also accompany the progression of some neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Although acute loss of hypothalamic neurons that produce appetite-stimulating neuropeptide Y (Npy) and agouti-related peptide (Agrp) in adult mice or in mice homozygous for the anorexia (anx) mutation causes aphagia, our understanding of the factors that help maintain appetite regulatory circuitry is limited. Here we identify a mutation (C19T) that converts an arginine to a tryptophan (R7W) in the TYRO3 protein tyrosine kinase 3 (Tyro3) gene, which resides within the anx critical interval, as contributing to the severity of anx phenotypes. Our observation that, like Tyro3(-/-) mice, anx/anx mice exhibit abnormal secondary platelet aggregation suggested that the C19T Tyro3 variant might have functional consequences. Tyro3 is expressed in the hypothalamus and other brain regions affected by the anx mutation, and its mRNA localization appeared abnormal in anx/anx brains by postnatal day 19 (P19). The presence of wild-type Tyro3 transgenes, but not an R7W-Tyro3 transgene, doubled the weight and lifespans of anx/anx mice and near-normal numbers of hypothalamic Npy-expressing neurons were present in Tyro3-transgenic anx/anx mice at P19. Although no differences in R7W-Tyro3 signal sequence function or protein localization were discernible in vitro, distribution of R7W-Tyro3 protein differed from that of Tyro3 protein in the cerebellum of transgenic wild-type mice. Thus, R7W-Tyro3 protein localization deficits are only detectable in vivo Further analyses revealed that the C19T Tyro3 mutation is present in a few other mouse strains, and hence is not the causative anx mutation, but rather an anx modifier. Our work shows that Tyro3 has prosurvival roles in the appetite regulatory circuitry and could also provide useful insights towards the development of interventions targeting

  8. The tyrosine kinase receptor Tyro3 enhances lifespan and neuropeptide Y (Npy neuron survival in the mouse anorexia (anx mutation

    Directory of Open Access Journals (Sweden)

    Dennis Y. Kim

    2017-05-01

    Full Text Available Severe appetite and weight loss define the eating disorder anorexia nervosa, and can also accompany the progression of some neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS. Although acute loss of hypothalamic neurons that produce appetite-stimulating neuropeptide Y (Npy and agouti-related peptide (Agrp in adult mice or in mice homozygous for the anorexia (anx mutation causes aphagia, our understanding of the factors that help maintain appetite regulatory circuitry is limited. Here we identify a mutation (C19T that converts an arginine to a tryptophan (R7W in the TYRO3 protein tyrosine kinase 3 (Tyro3 gene, which resides within the anx critical interval, as contributing to the severity of anx phenotypes. Our observation that, like Tyro3−/− mice, anx/anx mice exhibit abnormal secondary platelet aggregation suggested that the C19T Tyro3 variant might have functional consequences. Tyro3 is expressed in the hypothalamus and other brain regions affected by the anx mutation, and its mRNA localization appeared abnormal in anx/anx brains by postnatal day 19 (P19. The presence of wild-type Tyro3 transgenes, but not an R7W-Tyro3 transgene, doubled the weight and lifespans of anx/anx mice and near-normal numbers of hypothalamic Npy-expressing neurons were present in Tyro3-transgenic anx/anx mice at P19. Although no differences in R7W-Tyro3 signal sequence function or protein localization were discernible in vitro, distribution of R7W-Tyro3 protein differed from that of Tyro3 protein in the cerebellum of transgenic wild-type mice. Thus, R7W-Tyro3 protein localization deficits are only detectable in vivo. Further analyses revealed that the C19T Tyro3 mutation is present in a few other mouse strains, and hence is not the causative anx mutation, but rather an anx modifier. Our work shows that Tyro3 has prosurvival roles in the appetite regulatory circuitry and could also provide useful insights towards the development of interventions

  9. 血清肌酸激酶、C-反应蛋白和D-二聚体水平的测定在绞窄性肠梗阻早期诊断中的应用价值%Application value of level determination of serum creatine kinase, C-reactive protein and D-dimer in the early diagnosis of strangulated intestinal obstruction

    Institute of Scientific and Technical Information of China (English)

    张壮儒; 林楚怀; 杨永怀

    2016-01-01

    Objective: To analyze the value of level determination of serum creatine kinase, C-reactive protein and D-dimer in the early diagnosis of strangulated intestinal obstruction. Methods: 35 cases of strangulating intestinal obstruction patients admitted in our hospital from April 2013 to 2015 April were treated as observation group, and 35 patients admitted during the same period with simple obstruction were taken as the experimental group. Serum creatine kinase, C- reactive protein and D- dimer levels of 30 cases of healthy volunteers were examined as a control group. All patients received serum creatine kinase, C- reactive protein and D- dimer levels measured to compare their test results and analyze the correlation between the three indicators. Results: Compared with the control group, the levels of serum creatine kinase, C- reactive protein and D- dimer were not significantly different (P>0.05), while the serum creatine kinase, C- reactive protein and D- dimer levels of the observation group were significantly higher than those in the experimental group and the control group, the difference was statistically significant (P<0.05). The serum creatine kinase, C-reactive protein and D-dimer levels of the observation group among the three indexes were positively correlated. Conclusion: The detection of serum creatine kinase, C- reactive protein and D- dimer levels can effectively determine the level of strangulating intestinal obstruction, accurately determine the degree of injury patients and provide useful information for the treatment of late stage patients which is worthy of promotion.%目的:分析血清肌酸激酶、C-反应蛋白和 D-二聚体水平的测定在绞窄性肠梗阻早期诊断中的应用价值。方法:选择我院2013年4月—2015年4月收治的35例绞窄性肠梗阻患者作为观察组研究对象,和同期收治的35例单纯性肠梗阻患者作为实验组研究对象,同时,收集我院行血清肌酸激酶、C-反应蛋白

  10. Regulation of voltage-gated sodium current by endogenous Src family kinases in cochlear spiral ganglion neurons in culture.

    Science.gov (United States)

    Feng, Shuang; Pflueger, Melissa; Lin, Shuang-Xiu; Groveman, Bradley R; Su, Jiping; Yu, Xian-Min

    2012-04-01

    Voltage-gated sodium (Na+) and potassium (K+)channels have been found to be regulated by Src family kinases(SFKs).However, how these channels are regulated by SFKs in cochlear spiral ganglion neurons (SGNs) remains unknown.Here, we report that altering the activity of endogenous SFKs modulated voltage-gated Na+, but not K+, currents recorded in embryonic SGNs in culture. Voltage-gated Na+ current was suppressed by inhibition of endogenous SFKs or just Src and potentiated by the activation of these enzymes. Detailed investigations showed that under basal conditions, SFK inhibitor application did not significantly affect the voltage-dependent activation, but shifted the steady-state inactivation curves of Na+ currents and delayed the recovery of Na+ currents from inactivation. Application of Src specific inhibitor, Src40–58,not only shifted the inactivation curve but also delayed the recovery of Na+ currents and moved the voltage-dependent activation curve towards the left. The pre-inhibition of SFKs occluded all the effects induced by Src40–58 application, except the left shift of the activation curve. The activation of SFKs did not change either steady-state inactivation or recovery of Na+ currents, but caused the left shift of the activation curve.SFK inhibitor application effectively prevented all the effects induced by SFK activation, suggesting that both the voltage-dependent activation and steady-state inactivation of Na+ current are subjects of SFK regulation. The different effects induced by activation versus inhibition of SFKs implied that under basal conditions, endogenously active and inactive SFKs might be differentially involved in the regulation of voltage-gated Na+ channels in SGNs.

  11. Propofol Modulates Agonist-induced Transient Receptor Potential Vanilloid Subtype-1 Receptor Desensitization via a Protein Kinase Cε-dependent Pathway in Mouse Dorsal Root Ganglion Sensory Neurons

    Science.gov (United States)

    Wickley, Peter J.; Yuge, Ryo; Russell, Mary S.; Zhang, Hongyu; Sulak, Michael A.; Damron, Derek S.

    2011-01-01

    Background The activity of transient receptor potential vanilloid subtype-1 (TRPV1) receptors, key nociceptive transducers in dorsal root ganglion sensory neurons, is enhanced by protein kinase C ε (PKCε) activation. The intravenous anesthetic propofol has been shown to activate PKCε. Our objectives were to examine whether propofol modulates TRPV1 function in dorsal root ganglion neurons via activation of PKCε. Methods Lumbar dorsal root ganglion neurons from wild-type and PKCε-null mice were isolated and cultured for 24 h. Intracellular free Ca2+ concentration was measured in neurons by using fura-2 acetoxymethyl ester. The duration of pain-associated behaviors was also assessed. Phosphorylation of PKCε and TRPV1 and the cellular translocation of PKCε from cytosol to membrane compartments were assessed by immunoblot analysis. Results In wild-type neurons, repeated stimulation with capsaicin (100 nM) progressively decreased the transient rise in intracellular free Ca2+ concentration. After desensitization, exposure to propofol rescued the Ca2+ response. The resensitizing effect of propofol was absent in neurons obtained from PKCε-null mice. Moreover, the capsaicin-induced desensitization of TRPV1 was markedly attenuated in the presence of propofol in neurons from wild-type mice but not in neurons from PKCε-null mice. Propofol also prolonged the duration of agonist-induced pain associated behaviors in wild-type mice. In addition, propofol increased phosphorylation of PKCε as well as TRPV1 and stimulated translocation of PKCε from cytosolic to membrane fraction. Discussion Our results indicate that propofol modulates TRPV1 sensitivity to capsaicin and that this most likely occurs through a PKCε-mediated phosphorylation of TRPV1. PMID:20808213

  12. Inflammation in the uterus induces phosphorylated extracellular signal-regulated kinase and substance P immunoreactivity in dorsal root ganglia neurons innervating both uterus and colon in rats.

    Science.gov (United States)

    Li, Jichang; Micevych, Paul; McDonald, John; Rapkin, Andrea; Chaban, Victor

    2008-09-01

    In women, clinical studies suggest that pain syndromes such as irritable bowel syndrome and interstitial cystitis, which are associated with visceral hyperalgesia, are often comorbid with endometriosis and chronic pelvic pain. One of the possible explanations for this phenomenon is viscerovisceral cross-sensitization, in which increased nociceptive input from an inflamed pelvic organ sensitizes neurons that receive convergent input to the same dorsal root ganglion (DRG) from an unaffected visceral organ. Nociception induces up-regulation of cellular mechanisms such as phosphorylated extracellular signal-regulated kinase (pERK) and substance P (SP), neurotransmitters associated with induced pain sensation. The purpose of this study was to determine, in a rodent model, whether uterine inflammation increased the number of pERK- and SP-positive neurons that received input from both the uterus and the colon. Cell bodies of colonic and uterine DRG were retrogradely labeled with fluorescent tracer dyes microinjected into the colon/rectum and into the uterus. Ganglia were harvested for fluorescent microscopy to identify positively stained neurons. Approximately 6% of neurons were colon specific and 10% uterus specific. Among these uterus- or colon-specific neurons, up to 3-5% of DRG neurons in the lumbosacral neurons (L1-S3 levels) received input from both visceral organs. Uterine inflammation increased the number of pERK- and SP-immunoreactive DRG neurons innervating specifically colon, or innervating specifically uterus, and those innervating both organs. These results suggest that a localized inflammation activates primary visceral afferents, regardless of whether they innervate the affected organ. This visceral sensory integration in the DRG may underlie the observed comorbidity of female pelvic pain syndromes.

  13. X-linked creatine transporter deficiency: clinical aspects and pathophysiology.

    Science.gov (United States)

    van de Kamp, Jiddeke M; Mancini, Grazia M; Salomons, Gajja S

    2014-09-01

    Creatine transporter deficiency was discovered in 2001 as an X-linked cause of intellectual disability characterized by cerebral creatine deficiency. This review describes the current knowledge regarding creatine metabolism, the creatine transporter and the clinical aspects of creatine transporter deficiency. The condition mainly affects the brain while other creatine requiring organs, such as the muscles, are relatively spared. Recent studies have provided strong evidence that creatine synthesis also occurs in the brain, leading to the intriguing question of why cerebral creatine is deficient in creatine transporter deficiency. The possible mechanisms explaining the cerebral creatine deficiency are discussed. The creatine transporter knockout mouse provides a good model to study the disease. Over the past years several treatment options have been explored but no treatment has been proven effective. Understanding the pathogenesis of creatine transporter deficiency is of paramount importance in the development of an effective treatment.

  14. Upregulation of the Creatine Transporter Slc6A8 by Klotho

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    Ahmad Almilaji

    2014-11-01

    Full Text Available Background/Aims: The transmembrane Klotho protein contributes to inhibition of 1,25(OH2D3 formation. The extracellular domain of Klotho protein could function as an enzyme with e.g. β-glucuronidase activity, be cleaved off and be released into blood and cerebrospinal fluid. Klotho regulates several cellular transporters. Klotho protein deficiency accelerates the appearance of age related disorders including neurodegeneration and muscle wasting and eventually leads to premature death. The main site of Klotho protein expression is the kidney. Klotho protein is also appreciably expressed in other tissues including chorioid plexus. The present study explored the effect of Klotho protein on the creatine transporter CreaT (Slc6A8, which participates in the maintenance of neuronal function and survival. Methods: To this end cRNA encoding Slc6A8 was injected into Xenopus oocytes with and without additional injection of cRNA encoding Klotho protein. Creatine transporter CreaT (Slc6A8 activity was estimated from creatine induced current determined by two-electrode voltage-clamp. Results: Coexpression of Klotho protein significantly increased creatine-induced current in Slc6A8 expressing Xenopus oocytes. Coexpression of Klotho protein delayed the decline of creatine induced current following inhibition of carrier insertion into the cell membrane by brefeldin A (5 µM. The increase of creatine induced current by coexpression of Klotho protein in Slc6A8 expressing Xenopus oocytes was reversed by β-glucuronidase inhibitor (DSAL. Similarly, treatment of Slc6A8 expressing Xenopus oocytes with recombinant human alpha Klotho protein significantly increased creatine induced current. Conclusion: Klotho protein up-regulates the activity of creatine transporter CreaT (Slc6A8 by stabilizing the carrier protein in the cell membrane, an effect requiring β-glucuronidase activity of Klotho protein.

  15. Targeted deletion of the ERK5 MAP kinase impairs neuronal differentiation, migration, and survival during adult neurogenesis in the olfactory bulb.

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    Tan Li

    Full Text Available Recent studies have led to the exciting idea that adult-born neurons in the olfactory bulb (OB may be critical for complex forms of olfactory behavior in mice. However, signaling mechanisms regulating adult OB neurogenesis are not well defined. We recently reported that extracellular signal-regulated kinase (ERK 5, a MAP kinase, is specifically expressed in neurogenic regions within the adult brain. This pattern of expression suggests a role for ERK5 in the regulation of adult OB neurogenesis. Indeed, we previously reported that conditional deletion of erk5 in adult neurogenic regions impairs several forms of olfactory behavior in mice. Thus, it is important to understand how ERK5 regulates adult neurogenesis in the OB. Here we present evidence that shRNA suppression of ERK5 in adult neural stem/progenitor cells isolated from the subventricular zone (SVZ reduces neurogenesis in culture. By contrast, ectopic activation of endogenous ERK5 signaling via expression of constitutive active MEK5, an upstream activating kinase for ERK5, stimulates neurogenesis. Furthermore, inducible and conditional deletion of erk5 specifically in the neurogenic regions of the adult mouse brain interferes with cell cycle exit of neuroblasts, impairs chain migration along the rostral migratory stream and radial migration into the OB. It also inhibits neuronal differentiation and survival. These data suggest that ERK5 regulates multiple aspects of adult OB neurogenesis and provide new insights concerning signaling mechanisms governing adult neurogenesis in the SVZ-OB axis.

  16. Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases

    Science.gov (United States)

    Engstrom, Anna; Wang, Hao; Xia, Zhengui

    2015-01-01

    Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults. PMID:25967738

  17. Modulation of Kv3.1b potassium channel phosphorylation in auditory neurons by conventional and novel protein kinase C isozymes.

    Science.gov (United States)

    Song, Ping; Kaczmarek, Leonard K

    2006-06-02

    In fast-spiking neurons such as those in the medial nucleus of the trapezoid body (MNTB) in the auditory brainstem, Kv3.1 potassium channels are required for high frequency firing. The Kv3.1b splice variant of this channel predominates in the mature nervous system and is a substrate for phosphorylation by protein kinase C (PKC) at Ser-503. In resting neurons, basal phosphorylation at this site decreases Kv3.1 current, reducing neuronal ability to follow high frequency stimulation. We used a phospho-specific antibody to determine which PKC isozymes control serine 503 phosphorylation in Kv3.1b-tranfected cells and in auditory neurons in brainstem slices. By using isozyme-specific inhibitors, we found that the novel PKC-delta isozyme, together with the novel PKC-epsilon and conventional PKCs, contributed to the basal phosphorylation of Kv3.1b in MNTB neurons. In contrast, only PKC-epsilon and conventional PKCs mediate increases in phosphorylation produced by pharmacological activation of PKC in MNTB neurons or by metabotropic glutamate receptor activation in Kv3.1/mGluR1-cotransfected cells. We also measured the time course of dephosphorylation and recovery of basal phosphorylation of Kv3.1b following brief high frequency electrical stimulation of the trapezoid body, and we determined that the recovery process is mediated by both novel PKC-delta and PKC-epsilon isozymes and by conventional PKCs. The association between Kv3.1b and PKC isozymes was confirmed by reciprocal coimmunoprecipitation of Kv3.1b with multiple PKC isozymes. Our results suggest that the Kv3.1b channel is regulated by both conventional and novel PKC isozymes and that novel PKC-delta contributes specifically to the maintenance of basal phosphorylation in auditory neurons.

  18. Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway.

    Science.gov (United States)

    Mehta, Suresh L; Mendelev, Natalia; Kumari, Santosh; Andy Li, P

    2013-03-01

    Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and

  19. Efeito do exercício nas concentrações séricas de creatina cinase em triatletas de ultradistância Exercise effects on serum levels of creatine kinase in ultra-distance triathletes in the course of a competition period

    Directory of Open Access Journals (Sweden)

    Carolina Neis Machado

    2010-10-01

    supertreinamento, melhorando o desempenho, a saúde e a qualidade de vida do atleta.Triathlon is a popular sport with world wide participation. It combines three different endurance modalities - swimming, cycling and running - within a single event. There is a variety of distances on which triathlon events are made, the Ironman race being the longest. Many authors have already reported injury occurrence after intense exertion, either directly, through histological sarcomere alterations, or indirectly, over the quantification of specific muscle proteins concentration (injury biomarkers in the plasma. Among these markers of muscle injury, Myoglobin and Creatine Kinase stand out. In fact, creatine kinase is the most used biochemical indicator of muscle injury occurrence. Within this context, it is justified the purpose of this study, that intends to verify exercise effects on serum levels of creatine kinase in ultra-distance triathletes in the course of a competition period. Serum levels of CK from 10 triathletes who competed in the Ironman Brazil event, 2007 were evaluated. Blood analyses were done at five distinct periods: 19 days before Ironman Brazil competition (CK1, 48 hours before it (CK2, immediately after it (CK3, five days after the competition (CK4 and 12 days after the event (CK5. The results showed significant increase on CK concentrations at periods 3 and 4, when compared to the other evaluated periods. These alterations evidence the influence of the Ironman competition exhaustive exercise over the CK concentrations, revealing the possibility of muscle injuries development during the event. This fact enhances the importance of biomarkers' monitoring, like CK, that allow coaches and athletes to adapt training loads to increase their benefits and to avoid overtraining, improving performance, health and quality of life.

  20. Pivotal Role of Receptor-Interacting Protein Kinase 1 and Mixed Lineage Kinase Domain-Like in Neuronal Cell Death Induced by the Human Neuroinvasive Coronavirus OC43.

    Science.gov (United States)

    Meessen-Pinard, Mathieu; Le Coupanec, Alain; Desforges, Marc; Talbot, Pierre J

    2017-01-01

    Human coronaviruses (HCoV) are respiratory pathogens with neuroinvasive, neurotropic, and neurovirulent properties, highlighting the importance of studying the potential implication of these viruses in neurological diseases. The OC43 strain (HCoV-OC43) was reported to induce neuronal cell death, which may participate in neuropathogenesis. Here, we show that HCoV-OC43 harboring two point mutations in the spike glycoprotein (rOC/Us183-241) was more neurovirulent than the wild-type HCoV-OC43 (rOC/ATCC) in mice and induced more cell death in murine and human neuronal cells. To evaluate the role of regulated cell death (RCD) in HCoV-OC43-mediated neural pathogenesis, we determined if knockdown of Bax, a key regulator of apoptosis, or RIP1, a key regulator of necroptosis, altered the percentage of neuronal cell death following HCoV-OC43 infection. We found that Bax-dependent apoptosis did not play a significant role in RCD following infection, as inhibition of Bax expression mediated by RNA interference did not confer cellular protection against the cell death process. On the other hand, we demonstrated that RIP1 and MLKL were involved in neuronal cell death, as RIP1 knockdown and chemical inhibition of MLKL significantly increased cell survival after infection. Taken together, these results indicate that RIP1 and MLKL contribute to necroptotic cell death after HCoV-OC43 infection to limit viral replication. However, this RCD could lead to neuronal loss in the mouse CNS and accentuate the neuroinflammation process, reflecting the severity of neuropathogenesis. Because they are naturally neuroinvasive and neurotropic, human coronaviruses are suspected to participate in the development of neurological diseases. Given that the strain OC43 is neurovirulent in mice and induces neuronal cell death, we explored the neuronal response to infection by characterizing the activation of RCD. Our results revealed that classical apoptosis associated with the Bax protein does not play a

  1. The Caenorhabditis elegans matrix non-peptidase MNP-1 is required for neuronal cell migration and interacts with the Ror receptor tyrosine kinase CAM-1.

    Science.gov (United States)

    Craft, Teresa R; Forrester, Wayne C

    2017-04-01

    Directed cell migration is critical for metazoan development. During Caenorhabditis elegans development many neuronal, muscle and other cell types migrate. Multiple classes of proteins have been implicated in cell migration including secreted guidance cues, receptors for guidance cues and intracellular proteins that respond to cues to polarize cells and produce the forces that move them. In addition, cell surface and secreted proteases have been identified that may clear the migratory route and process guidance cues. We report here that mnp-1 is required for neuronal cell and growth cone migrations. MNP-1 is expressed by migrating cells and functions cell autonomously for cell migrations. We also find a genetic interaction between mnp-1 and cam-1, which encodes a Ror receptor tyrosine kinase required for some of the same cell migrations.

  2. PI3 kinase/Akt activation mediates estrogen and IGF-1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson's disease.

    Science.gov (United States)

    Quesada, Arnulfo; Lee, Becky Y; Micevych, Paul E

    2008-04-01

    Recently, using the medial forebrain bundle (MFB) 6-hydroxydopmaine (6-OHDA) lesion rat model of Parkinson's disease (PD), we have demonstrated that blockade of central IGF-1 receptors (IGF-1R) attenuated estrogen neuroprotection of substantia nigra pars compacta (SNpc) DA neurons, but exacerbated 6-OHDA lesions in IGF-1 only treated rats (Quesada and Micevych [2004]: J Neurosci Res 75:107-116). This suggested that the IGF-1 system is a central mechanism through which estrogen acts to protect the nigrostriatal DA system. Moreover, these results also suggest that IGF-1R-induced intracellular signaling pathways are involved in the estrogen mechanism that promotes neuronal survival. In vitro, two convergent intracellular signaling pathways used by estrogen and IGF-1, the mitogen-activated protein kinase (MAPK/ERK), and phosphatidyl-inositol-3-kinase/Akt (PI3K/Akt), have been demonstrated to be neuroprotective. Continuous central infusions of MAPK/ERK and PI3K/Akt inhibitors were used to test the hypothesis that one or both of these signal transduction pathways mediates estrogen and/or IGF-1 neuroprotection of SNpc DA neurons after a unilateral administration of 6-OHDA into the MFB of rats. Motor behavior tests and tyrosine hydroxylase immunoreactivity revealed that the inhibitor of the PI3K/Akt pathway (LY294002) blocked the survival effects of both estrogen and IGF-1, while an inhibitor of the MAPK/ERK signaling (PD98059) was ineffective. Western blot analyses showed that estrogen and IGF-1 treatments increased PI3K/Akt activation in the SN; however, MAPK/ERK activation was decreased in the SN. Indeed, continuous infusions of inhibitors blocked phosphorylation of PI3K/Akt and MAPK/ERK. These findings indicate that estrogen and IGF-1-mediated SNpc DA neuronal protection is dependent on PI3K/Akt signaling, but not on the MAPK/ERK pathway.

  3. Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice.

    Directory of Open Access Journals (Sweden)

    Stephanie A Shumar

    Full Text Available Pantothenate kinase-associated neurodegeneration, PKAN, is an inherited disorder characterized by progressive impairment in motor coordination and caused by mutations in PANK2, a human gene that encodes one of four pantothenate kinase (PanK isoforms. PanK initiates the synthesis of coenzyme A (CoA, an essential cofactor that plays a key role in energy metabolism and lipid synthesis. Most of the mutations in PANK2 reduce or abolish the activity of the enzyme. This evidence has led to the hypothesis that lower CoA might be the underlying cause of the neurodegeneration in PKAN patients; however, no mouse model of the disease is currently available to investigate the connection between neuronal CoA levels and neurodegeneration. Indeed, genetic and/or dietary manipulations aimed at reducing whole-body CoA synthesis have not produced a desirable PKAN model, and this has greatly hindered the discovery of a treatment for the disease.Cellular CoA levels are tightly regulated by a balance between synthesis and degradation. CoA degradation is catalyzed by two peroxisomal nudix hydrolases, Nudt7 and Nudt19. In this study we sought to reduce neuronal CoA in mice through the alternative approach of increasing Nudt7-mediated CoA degradation. This was achieved by combining the use of an adeno-associated virus-based expression system with the synapsin (Syn promoter. We show that mice with neuronal overexpression of a cytosolic version of Nudt7 (scAAV9-Syn-Nudt7cyt exhibit a significant decrease in brain CoA levels in conjunction with a reduction in motor coordination. These results strongly support the existence of a link between CoA levels and neuronal function and show that scAAV9-Syn-Nudt7cyt mice can be used to model PKAN.

  4. IMPACT is a developmentally regulated protein in neurons that opposes the eukaryotic initiation factor 2α kinase GCN2 in the modulation of neurite outgrowth.

    Science.gov (United States)

    Roffé, Martín; Hajj, Glaucia N M; Azevedo, Hátylas F; Alves, Viviane S; Castilho, Beatriz A

    2013-04-12

    The product of the mouse Imprinted and Ancient gene, IMPACT, is preferentially expressed in neurons. We have previously shown that IMPACT overexpression inhibits the activation of the protein kinase GCN2, which signals amino acid starvation. GCN2 phosphorylates the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), resulting in inhibition of general protein synthesis but increased translation of specific messages, such as ATF4. GCN2 is also involved in the regulation of neuronal functions, controlling synaptic plasticity, memory, and feeding behavior. We show here that IMPACT abundance increases during differentiation of neurons and neuron-like N2a cells, whereas GCN2 displays lowered activation levels. Upon differentiation, IMPACT associates with translating ribosomes, enhances translation initiation, and down-regulates the expression of ATF4. We further show that endogenous IMPACT promotes neurite outgrowth whereas GCN2 is a strong inhibitor of spontaneous neuritogenesis. Together, these results uncover the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system.

  5. ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY).

    Science.gov (United States)

    Koshoridze, N; Kuchukashvili, Z; Menabde, K; Lekiashvili, Sh; Koshoridze, M

    2016-02-01

    Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up-regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability.

  6. Creatine supplementation and swimming performance.

    Science.gov (United States)

    Leenders, N M; Lamb, D R; Nelson, T E

    1999-09-01

    The purpose of this study was to determine if oral creatine (CR) ingestion, compared to a placebo (PL), would enable swimmers to maintain a higher swimming velocity across repeated interval sets over 2 weeks of supplementation. Fourteen female and 18 male university swimmers consumed a PL during a 2-week baseline period. Using a randomized, double-blind design, during the next 2 weeks subjects consumed either CR or PL. Swimming velocity was assessed twice weekly during 6 X 50-m swims and once weekly during 10 X 25-yd swims. There was no effect of CR on the 10 X 25-yd interval sets for men and women and no effect on the 6 X 50-m interval sets for women. In contrast, for men, CR significantly improved mean overall swimming velocity in the 6 X 50-m interval after 2 weeks of supplementation, whereas PL had no effect. Although ineffective in women, CR supplementation apparently enables men to maintain a faster mean overall swimming velocity during repeated swims each lasting about 30 s; however, CR was not effective for men in repeated swims each lasting about 10 - 15 s.

  7. Electrical stimulation with periodic alternating intervals stimulates neuronal cells to produce neurotrophins and cytokines through activation of mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yamamoto, Kenta; Yamamoto, Toshiro; Honjo, Kenichi; Ichioka, Hiroaki; Oseko, Fumishige; Kishida, Tsunao; Mazda, Osam; Kanamura, Narisato

    2015-12-01

    Peripheral neuropathy is a representative complication of dental surgery. Electrical therapy, based on electrical stimulation with periodic alternating intervals (ES-PAI), may promote nerve regeneration after peripheral nerve injury in a non-invasive manner, potentially providing an effective therapy for neuropathy. This study aimed to analyze the molecular mechanisms underlying the nerve recovery stimulated by ES-PAI. In brief, ES-PAI was applied to a neuronal cell line, Neuro2A, at various intensities using the pulse generator apparatus, FREUDE. Cell viability, neurotrophin mRNA expression, and cytokine production were examined using a tetrazolium-based assay, real-time RT-PCR, and ELISA, respectively. Mitogen-activated protein kinase (MAPK) signaling was assessed using flow cytometry. It was found that ES-PAI increased the viability of cells and elevated expression of nerve growth factor (NGF) and neurotrophin-3 (NT-3); ESPAI also augmented vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) expression, which was restored by addition of p38 inhibitors. Phosphorylation of p38 and extracellular signal-regulated kinase 1/2 (ERK-1/2) was augmented by ES-PAI. Hence, ES-PAI may ameliorate peripheral neuropathy by promoting neuronal cell proliferation and production of neurogenic factors by activating p38 and ERK-1/2 pathways.

  8. Creatine and Caffeine: Considerations for Concurrent Supplementation.

    Science.gov (United States)

    Trexler, Eric T; Smith-Ryan, Abbie E

    2015-12-01

    Nutritional supplementation is a common practice among athletes, with creatine and caffeine among the most commonly used ergogenic aids. Hundreds of studies have investigated the ergogenic potential of creatine supplementation, with consistent improvements in strength and power reported for exercise bouts of short duration (≤ 30 s) and high intensity. Caffeine has been shown to improve endurance exercise performance, but results are mixed in the context of strength and sprint performance. Further, there is conflicting evidence from studies comparing the ergogenic effects of coffee and caffeine anhydrous supplementation. Previous research has identified independent mechanisms by which creatine and caffeine may improve strength and sprint performance, leading to the formulation of multi-ingredient supplements containing both ingredients. Although scarce, research has suggested that caffeine ingestion may blunt the ergogenic effect of creatine. While a pharmacokinetic interaction is unlikely, authors have suggested that this effect may be explained by opposing effects on muscle relaxation time or gastrointestinal side effects from simultaneous consumption. The current review aims to evaluate the ergogenic potential of creatine and caffeine in the context of high-intensity exercise. Research directly comparing coffee and caffeine anhydrous is discussed, along with previous studies evaluating the concurrent supplementation of creatine and caffeine.

  9. Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent protein kinase II in resting sensory neurons.

    Science.gov (United States)

    Kostic, Sandra; Pan, Bin; Guo, Yuan; Yu, Hongwei; Sapunar, Damir; Kwok, Wai-Meng; Hudmon, Andy; Wu, Hsiang-En; Hogan, Quinn H

    2014-09-01

    Calcium/calmodulin-dependent protein kinase II (CaMKII) is recognized as a key element in encoding depolarization activity of excitable cells into facilitated voltage-gated Ca(2+) channel (VGCC) function. Less is known about the participation of CaMKII in regulating VGCCs in resting cells. We examined constitutive CaMKII control of Ca(2+) currents in peripheral sensory neurons acutely isolated from dorsal root ganglia (DRGs) of adult rats. The small molecule CaMKII inhibitor KN-93 (1.0μM) reduced depolarization-induced ICa by 16-30% in excess of the effects produced by the inactive homolog KN-92. The specificity of CaMKII inhibition on VGCC function was shown by the efficacy of the selective CaMKII blocking peptide autocamtide-2-related inhibitory peptide in a membrane-permeable myristoylated form, which also reduced VGCC current in resting neurons. Loss of VGCC currents is primarily due to reduced N-type current, as application of mAIP selectively reduced N-type current by approximately 30%, and prior N-type current inhibition eliminated the effect of mAIP on VGCCs, while prior block of L-type channels did not reduce the effect of mAIP on total ICa. T-type currents were not affected by mAIP in resting DRG neurons. Transduction of sensory neurons in vivo by DRG injection of an adeno-associated virus expressing AIP also resulted in a loss of N-type currents. Together, these findings reveal a novel molecular adaptation whereby sensory neurons retain CaMKII support of VGCCs despite remaining quiescent.

  10. Levodopa activates apoptosis signaling kinase 1 (ASK1) and promotes apoptosis in a neuronal model: implications for the treatment of Parkinson's disease.

    Science.gov (United States)

    Liedhegner, Elizabeth A Sabens; Steller, Kelly M; Mieyal, John J

    2011-10-17

    Oxidative stress is implicated in the etiology of Parkinson's disease (PD), the second most common neurodegenerative disease. PD is treated with chronic administration of l-3,4-dihydroxyphenylalanine (levodopa, L-DOPA), and typically, increasing doses are used during progression of the disease. Paradoxically, L-DOPA is a pro-oxidant and induces cell death in cellular models of PD through disruption of sulfhydryl homeostasis involving loss of the thiol-disulfide oxidoreductase functions of the glutaredoxin (Grx1) and thioredoxin (Trx1) enzyme systems [Sabens, E. A., Distler, A. M., and Mieyal, J. J. (2010) Biochemistry 49 (12), 2715-2724]. Considering this loss of both Grx1 and Trx1 activities upon L-DOPA treatment, we sought to elucidate the mechanism(s) of L-DOPA-induced apoptosis. In other contexts, both the NFκB (nuclear factor κB) pathway and the ASK1 (apoptosis signaling kinase 1) pathway have been shown to be regulated by both Grx1 and Trx1, and both pathways have been implicated in cell death signaling in model systems of PD. Moreover, mixed lineage kinase (MLK) has been considered as a potential therapeutic target for PD. Using SHSY5Y cells as model dopaminergic neurons, we found that NFκB activity was not altered by L-DOPA treatment, and the selective MLK inhibitor (CEP-1347) did not protect the cells from L-DOPA. In contrast, ASK1 was activated with L-DOPA treatment as indicated by phosphorylation of its downstream mitogen-activated protein kinases (MAPK), p38 and JNK. Chemical inhibition of either p38 or JNK provided protection from L-DOPA-induced apoptosis. Moreover, direct knockdown of ASK1 protected from L-DOPA-induced neuronal cell death. These results identify ASK1 as the main pro-apoptotic pathway activated in response to L-DOPA treatment, implicating it as a potential target for adjunct therapy in PD.

  11. Reciprocal signals between microglia and neurons regulate alpha-synuclein secretion by exophagy through a neuronal cJU-N-Nterminal kinase-signaling axis

    DEFF Research Database (Denmark)

    Christensen, Dan Ploug; Ejlerskov, Patrick; Rasmussen, Izabela

    2016-01-01

    Background: Secretion of proteopathic alpha-synuclein (alpha-SNC) species from neurons is a suspected driving force in the propagation of Parkinson's disease (PD). We have previously implicated exophagy, the exocytosis of autophagosomes, as a dominant mechanism of alpha-SNC secretion in different...

  12. Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro.

    Science.gov (United States)

    Yang, Y-F; Chen, Z; Hu, S-L; Hu, J; Li, B; Li, J-T; Wei, L-J; Qian, Z-M; Lin, J-K; Feng, H; Zhu, G

    2011-11-24

    Neuronal Toll-like receptors (TLRs)-2 and -4 have been shown to play a pivotal role in ischemic brain injury, and the interleukin-1 receptor associated kinases (IRAKs) are considered to be the key signaling molecules involved downstream of TLRs. Here, we investigated the expression levels of IRAK-1 and -4 and the effects of IRAK-1/4 inhibition on brain ischemic insult and neuronal hypoxia-induced injury. Male Sprague-Dawley (SD) rats and the rat neuroblastoma B35 cell line were used in these experiments. Permanent middle cerebral artery occlusion (MCAO) was induced by the intraluminal filament technique, and B35 cells were stimulated with the hypoxia-mimetic, cobalt chloride (CoCl(2)). Following induction of hypoxia/ischemia (H/I), B35 cells and cerebral cortical neurons expressed higher levels of IRAK-1 and -4. Furthermore, IRAK-1/4 inhibition decreased the mortality rate, functional deficits, and ischemic infarct volume by 7 days after MCAO. Similarly, IRAK-1/4 inhibition attenuated CoCl(2)-induced cytotoxicity and apoptosis in B35 cells in vitro. Our results show that IRAK-1/4 inhibition decreased the nuclear translocation of the nuclear factor-kappaB (NF-κB) p65 subunit, the levels of activated (phosphorylated) c-jun N-terminal kinase (JNK) and cleaved caspase-3, and the secretion of TNF-α and IL-6 in B35 cells at 6 h after CoCl(2) treatment. These data suggest that IRAK-1/4 inhibition plays a neuroprotective role in H/I-induced brain injury.

  13. Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men.

    Science.gov (United States)

    Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik; Vranes, Milan

    2016-09-01

    In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P creatine for improved bioenergetics in energy-demanding tissues.

  14. Disruption of zebrafish cyclin G-associated kinase (GAK function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development

    Directory of Open Access Journals (Sweden)

    Szeto Daniel P

    2010-01-01

    Full Text Available Abstract Background The J-domain-containing protein auxilin, a critical regulator in clathrin-mediated transport, has been implicated in Drosophila Notch signaling. To ask if this role of auxilin is conserved and whether auxilin has additional roles in development, we have investigated the functions of auxilin orthologs in zebrafish. Results Like mammals, zebrafish has two distinct auxilin-like molecules, auxilin and cyclin G-associated kinase (GAK, differing in their domain structures and expression patterns. Both zebrafish auxilin and GAK can functionally substitute for the Drosophila auxilin, suggesting that they have overlapping molecular functions. Still, they are not completely redundant, as morpholino-mediated knockdown of the ubiquitously expressed GAK alone can increase the specification of neuronal cells, a known Notch-dependent process, and decrease the expression of Her4, a Notch target gene. Furthermore, inhibition of GAK function caused an elevated level of apoptosis in neural tissues, resulting in severe degeneration of neural structures. Conclusion In support of the notion that endocytosis plays important roles in Notch signaling, inhibition of zebrafish GAK function affects embryonic neuronal cell specification and Her4 expression. In addition, our analysis suggests that zebrafish GAK has at least two functions during the development of neural tissues: an early Notch-dependent role in neuronal patterning and a late role in maintaining the survival of neural cells.

  15. c-Jun N-terminal kinase phosphorylation of MARCKSL1 determines actin stability and migration in neurons and in cancer cells.

    Science.gov (United States)

    Björkblom, Benny; Padzik, Artur; Mohammad, Hasan; Westerlund, Nina; Komulainen, Emilia; Hollos, Patrik; Parviainen, Lotta; Papageorgiou, Anastassios C; Iljin, Kristiina; Kallioniemi, Olli; Kallajoki, Markku; Courtney, Michael J; Mågård, Mats; James, Peter; Coffey, Eleanor T

    2012-09-01

    Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated migration underlies neurological birth defects and cancer metastasis. MARCKS-like protein 1 (MARCKSL1) is widely expressed in nervous tissue, where, like Jun N-terminal protein kinase (JNK), it is required for neural tube formation, though the mechanism is unknown. Here we show that MARCKSL1 is directly phosphorylated by JNK on C-terminal residues (S120, T148, and T183). This phosphorylation enables MARCKSL1 to bundle and stabilize F-actin, increase filopodium numbers and dynamics, and retard migration in neurons. Conversely, when MARCKSL1 phosphorylation is inhibited, actin mobility increases and filopodium formation is compromised whereas lamellipodium formation is enhanced, as is cell migration. We find that MARCKSL1 mRNA is upregulated in a broad range of cancer types and that MARCKSL1 protein is strongly induced in primary prostate carcinomas. Gene knockdown in prostate cancer cells or in neurons reveals a critical role for MARCKSL1 in migration that is dependent on the phosphorylation state; phosphomimetic MARCKSL1 (MARCKSL1(S120D,T148D,T183D)) inhibits whereas dephospho-MARCKSL1(S120A,T148A,T183A) induces migration. In summary, these data show that JNK phosphorylation of MARCKSL1 regulates actin homeostasis, filopodium and lamellipodium formation, and neuronal migration under physiological conditions and that, when ectopically expressed in prostate cancer cells, MARCKSL1 again determines cell movement.

  16. 探讨IFCC原始参考方法与临床常规方法测定血清肌酸激酶结果的相关性%Study the Relativity of Testing Serum Creatine Kinase Results with IFCC Primary Reference Method and Clinical Conventional Methods

    Institute of Scientific and Technical Information of China (English)

    周铁成; 张莹; 童开; 郝晓柯

    2011-01-01

    目的 分析IFCC原始参考方法与临床常规方法测定血清肌酸激酶结果的相关性,并探讨血清CK测定结果的准确度与一致性.方法 依据IFCC的参考测量程序建立CK酶活性测定的参考方法,用参考方法测定ERMR-AD455CK参考品,验证方法的准确性,并对其精密度进行方法学评价.按照NCCLS EP9-A方案进行参考方法与临床常规方法CK检测结果的比较.分析两种方法间的相关系数和允许偏差.结果 参考方法与临床常规方法CK检测结果相关性良好,回归方程Y=0.967X-2.339 7,r2=0.998 7,系统误差(SE)在CLIA'88的误差允许范围内.结论 该室CK的参考方法已建立,临床常规方法与参考方法间比对,验证提高了临床血清CK测定结果的准确性和一致性.%Objective To study the relativity of testing serum creatine kinase results with IFCC primary reference methods and clinical conventional methods, analyse accuracy and consistency of the results. Methods To establish the reference method measure catalytic activity concentration of CK at 37℃ according to IFCC primary procedure. Measured ERMR_AD455CK by using the reference method and evaluated the precision,a calibrator was prepared,its value for CK was assigned with the reference method. Compared the results between IFCC primary reference methods and clinical conventional methods by EP-9A of NCCLS. Analyse correlation coefficient and the allowable deviation between IFCC primary reference methods and clinical conventional methods. Results There was good correlation between IFCC primary reference methods and clinical conventional methods. The regression equation was Y= 0. 967X - 2. 339 7 ,r2 =0. 998 7. Relative deviation was in the rang of permissible error of CLIA'88. Conclusion The reference method of CK at 37℃ had been already established. This will improved the accuracy and comparability of the results of serum CK.

  17. Serum creatine kinase and lactate dehydrogenase activities in ...

    African Journals Online (AJOL)

    hypothyroidism is defined by the finding of elevated serum. TSH concentrations ... Access this article online. Quick Response ... in thyroid disorders condition is higher in women than men and increases with ..... thyroid diseases and pregnancy.

  18. Creatine Kinase Clinical Considerations: Ethnicity, Gender and Genetics

    Science.gov (United States)

    2009-10-01

    contract. CK has five functional forms or isoenzymes, three are cytosolic and two are mitochondrial . The cytosolic forms are composed of two subunits...muscle (33). Both mitochondrial isoenzymes, non-sarcomeric and sarcomeric, are octamers consisting of four dimers each (5). The use of serum CK as a...and to detect various myopathies . However, the large variability in baseline levels may reflect prior exercise (23), muscle damage (7, 18), a

  19. Creatine kinase and blood pressure: Clinical and therapeutic implications

    NARCIS (Netherlands)

    Oudman, I.

    2013-01-01

    Hypertension affects more than one billion people worldwide and is one of the most powerful contributors to cardiovascular morbidity and mortality. Black people of African descent are more often affected by the disease. One of the biological factors contributing to this difference is the enzyme

  20. Periodontal status and serum creatine kinase levels among young ...

    African Journals Online (AJOL)

    2015-12-02

    Dec 2, 2015 ... and Sports Medicine, Previous Saudi National Soccer Team Physician, Prince Faisal Bin Fahad Bin ... The present cross‑sectional study was based on the .... muscle retains the ability to fully regenerate functional architecture.

  1. Changes in neutrophil count, creatine kinase and muscle soreness ...

    African Journals Online (AJOL)

    Department of Sport, Rehabilitation and Dental Sciences. Tshwane University ... screening in the Exercise Testing Laboratory (ETL). During the first visit .... blood analyser, which uses a colorometric assay procedure. (Boehringer ... Significance was set at p<0.05. ..... the entire period (before exercise through 144 h after). As.

  2. [Evaluation of the Creatine Kinase MB Activity Assay Kit].

    Science.gov (United States)

    Okubo, Manabu; Kimura, Shigeki; Matsui, Masahiko; Suehisa, Etsuji; Hidaka, Yoh

    2014-11-01

    CK-MB activity, which is measured by the immunoinhibition method, is an important marker for use in the diagnosis of acute coronary syndromes. In the present study, we evaluated the basal performance of a recently improved CK-MB activity kit, "L-system CK-MB," in which the activity of mitochondrial CK subunits is inhibited. Within-run and between-day precision were in the range of 1.9-2.3% and 3.2-6.0%, respectively. Diluted linearity and limit of detection were determined to be 600 U/L and 0.8 U/L, respectively. The use of L-system CK-MB allowed the inhibition of the activity of 98.1% of sarcomeric mitochondrial CK, 97.7% of ubiquitous mitochondrial CK, and 99.9% of CK-MM. The correlation coefficient (r) between CK-MB activity and CK-MB protein was 0.968. However, we found 4 cases showing CK-MB activity significantly higher than the protein concentration. Increased CK-BB activity was detected by electrophoresis in these cases. In some patients with malignant tumors, the presence of CK-immunoglobulin complex also lead to elevated CK-MB concentrations. Thus, the discrepancy in the CK-MB activity and the protein concentration may be caused by the presence of CK-BB and/or CK-immunoglobulin complex. More attention needs to be focused on samples with high CK-MB protein concentrations, especially when the CK-MB/CK ratio is high.

  3. Effect of c-Jun NH2-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    HONG Ming-yan; GAO Jun-ling; CUI Jian-zhong; WANG Kai-jie; TIAN Yan-xia; LI Ran; WANG Hai-tao; WANG Huan

    2012-01-01

    Background Activation of c-Jun NH2-terminal kinase (JNK) has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury (TBI).However,the underlying molecular pathway remains unclear.Our study assessed whether JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.Methods A total of 186 male Sprague-Dawley (SD) rats (300-350 g) were used in this study.By randomized block method rats were randomly divided into four groups:sham-operated (n=46),TBI (n=60),TBI + dimethyl sulfoxide (DMSO) (n=40),and TBI + SP600125 (n=40).JNK was treated with SP600125,a specific JNK inhibitor.JNK,p-P53,Beclin-1,damage-regulated autophagy modulator (DRAM) and p-bcl-2 were evaluated by Western blotting analysis.The cellular localization and expression of Beclin-1 and DRAM was observed by immunofluorescence and immunohistochemistry,and the expression of Beclin-1-Bcl-2/Bcl-xL complexes was evaluated by immunoprecipitation.Multiple-group comparisons were conducted using analysis of variance (ANOVA).P values of less than 0.05 were considered statistically significant.Results It was observed that the expression of JNK,p-P53,Beclin-1,DRAM and p-bcl-2 was increasing after TBI,and the expression of Beclin-1 and DRAM was mainly located in the cytoplasm of neurons.But these were significantly inhibited in SP600125 group compared with sham group and TBI+SP600125 group (P <0.05).The expression of Beclin-1-Bcl-2/Bcl-xL complexes was reduced after TBI.Conclusion JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.

  4. Histone hyperacetylation up-regulates protein kinase Cδ in dopaminergic neurons to induce cell death: relevance to epigenetic mechanisms of neurodegeneration in Parkinson disease.

    Science.gov (United States)

    Jin, Huajun; Kanthasamy, Arthi; Harischandra, Dilshan S; Kondru, Naveen; Ghosh, Anamitra; Panicker, Nikhil; Anantharam, Vellareddy; Rana, Ajay; Kanthasamy, Anumantha G

    2014-12-12

    The oxidative stress-sensitive protein kinase Cδ (PKCδ) has been implicated in dopaminergic neuronal cell death. However, little is known about the epigenetic mechanisms regulating PKCδ expression in neurons. Here, we report a novel mechanism by which the PKCδ gene can be regulated by histone acetylation. Treatment with histone deacetylase (HDAC) inhibitor sodium butyrate (NaBu) induced PKCδ expression in cultured neurons, brain slices, and animal models. Several other HDAC inhibitors also mimicked NaBu. The chromatin immunoprecipitation analysis revealed that hyperacetylation of histone H4 by NaBu is associated with the PKCδ promoter. Deletion analysis of the PKCδ promoter mapped the NaBu-responsive element to an 81-bp minimal promoter region. Detailed mutagenesis studies within this region revealed that four GC boxes conferred hyperacetylation-induced PKCδ promoter activation. Cotransfection experiments and Sp inhibitor studies demonstrated that Sp1, Sp3, and Sp4 regulated NaBu-induced PKCδ up-regulation. However, NaBu did not alter the DNA binding activities of Sp proteins or their expression. Interestingly, a one-hybrid analysis revealed that NaBu enhanced transcriptional activity of Sp1/Sp3. Overexpression of the p300/cAMP-response element-binding protein-binding protein (CBP) potentiated the NaBu-mediated transactivation potential of Sp1/Sp3, but expressing several HDACs attenuated this effect, suggesting that p300/CBP and HDACs act as coactivators or corepressors in histone acetylation-induced PKCδ up-regulation. Finally, using genetic and pharmacological approaches, we showed that NaBu up-regulation of PKCδ sensitizes neurons to cell death in a human dopaminergic cell model and brain slice cultures. Together, these results indicate that histone acetylation regulates PKCδ expression to augment nigrostriatal dopaminergic cell death, which could contribute to the progressive neuropathogenesis of Parkinson disease. © 2014 by The American Society

  5. Interleukin-1 beta induction of neuron apoptosis depends on p38 mitogen-activated protein kinase activity after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Xin-jia WANG; Kang-mei KONG; Wei-li QI; Wei-lian YE; Pei-song SONG

    2005-01-01

    Aim: Interleukin-1 beta (IL-1β) has been implicated as an extracellular signal in the initiation of apoptosis in neurons and oligodendrocytes after spinal cord injury (SCI). To further characterize the apoptotic cascade initiated by IL-1β after SCI, we examined the expression of IL-1 β, p38 mitogen-activated protein kinase (p38 MAPK) and caspase-3 after SCI, and further investigated whether p38 MAPK was involved in neuron apoptosis induced by IL-1 β. Methods: Adult rats were given contusion SCI at the T-10 vertebrae level with a weight-drop impactor (10 g weight dropped 25.0 mm). The expression levels of IL-1β, p38 MAPK and caspase-3after SCI were assessed with Western blots, immunohistochemistry staining, and real time reverse transcription polymerase chain reactions (RT-PCR). Neuron apoptosis was assessed with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method. Results:Increased levels of IL-1β and p38 MAPK were observed soon after injury, with a peak in expression levels within 6 h of injury. By 24 h after injury, caspase-3expression was markedly increased in the injured spinal cord. TUNEL-positive cells were first observed in the lesioned area 6 h after SCI. The largest number of TUNEL-positive cells was observed at 24 h post-SCI. Intrathecal injection of the IL-1 receptor antagonist IL-1Ra significantly reduced expression of p38 MAPK and caspase-3, and reduced the number of TUNEL-positive cells. Moreover,intrathecal injection of an inhibitor of p38 MAPK, SB203580, also significantly reduced the expression of caspase-3, and reduced the number of TUNEL-positive cells in the injured spinal cord. Conclusion: The p38MAPK signaling pathway plays an important role in IL-1β mediated induction of neuron apoptosis following SCI in rats.

  6. Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface.

    Science.gov (United States)

    Jinadasa, Tushare; Szabó, Elöd Z; Numat, Masayuki; Orlowski, John

    2014-07-25

    Strict regulation of intra- and extracellular pH is an important determinant of nervous system function as many voltage-, ligand-, and H(+)-gated cationic channels are exquisitely sensitive to transient fluctuations in pH elicited by neural activity and pathophysiologic events such as hypoxia-ischemia and seizures. Multiple Na(+)/H(+) exchangers (NHEs) are implicated in maintenance of neural pH homeostasis. However, aside from the ubiquitous NHE1 isoform, their relative contributions are poorly understood. NHE5 is of particular interest as it is preferentially expressed in brain relative to other tissues. In hippocampal neurons, NHE5 regulates steady-state cytoplasmic pH, but intriguingly the bulk of the transporter is stored in intracellular vesicles. Here, we show that NHE5 is a direct target for phosphorylation by the AMP-activated protein kinase (AMPK), a key sensor and regulator of cellular energy homeostasis in response to metabolic stresses. In NHE5-transfected non-neuronal cells, activation of AMPK by the AMP mimetic AICAR or by antimycin A, which blocks aerobic respiration and causes acidification, increased cell surface accumulation and activity of NHE5, and elevated intracellular pH. These effects were effectively blocked by the AMPK antagonist compound C, the NHE inhibitor HOE694, and mutation of a predicted AMPK recognition motif in the NHE5 C terminus. This regulatory pathway was also functional in primary hippocampal neurons, where AMPK activation of NHE5 protected the cells from sustained antimycin A-induced acidification. These data reveal a unique role for AMPK and NHE5 in regulating the pH homeostasis of hippocampal neurons during metabolic stress.

  7. Brain-derived neurotrophic factor and epidermal growth factor activate neuronal m-calpain via mitogen-activated protein kinase-dependent phosphorylation.

    Science.gov (United States)

    Zadran, Sohila; Jourdi, Hussam; Rostamiani, Karoline; Qin, Qingyu; Bi, Xiaoning; Baudry, Michel

    2010-01-20

    Calpain is a calcium-dependent protease that plays a significant role in synaptic plasticity, cell motility, and neurodegeneration. Two major calpain isoforms are present in brain, with mu-calpain (calpain1) requiring micromolar calcium concentrations for activation and m-calpain (calpain2) needing millimolar concentrations. Recent studies in fibroblasts indicate that epidermal growth factor (EGF) can activate m-calpain independently of calcium via mitogen-activated protein kinase (MAPK)-mediated phosphorylation. In neurons, MAPK is activated by both brain-derived neurotrophic factor (BDNF) and EGF. We therefore examined whether these growth factors could activate m-calpain by MAPK-dependent phosphorylation using cultured primary neurons and HEK-TrkB cells, both of which express BDNF and EGF receptors. Calpain activation was monitored by quantitative analysis of spectrin degradation and by a fluorescence resonance energy transfer (FRET)-based assay, which assessed the truncation of a calpain-specific peptide flanked by the FRET fluorophore pair DABCYL and EDANS. In both cell types, BDNF and EGF rapidly elicited calpain activation, which was completely blocked by MAPK and calpain inhibitors. BDNF stimulated m-calpain but not mu-calpain serine phosphorylation, an effect also blocked by MAPK inhibitors. Remarkably, BDNF- and EGF-induced calpain activation was preferentially localized in dendrites and dendritic spines of hippocampal neurons and was associated with actin polymerization, which was prevented by calpain inhibition. Our results indicate that, in cultured neurons, both BDNF and EGF activate m-calpain by MAPK-mediated phosphorylation. These results strongly support a role for calpain in synaptic plasticity and may explain why m-calpain, although widely expressed in CNS, requires nonphysiological calcium levels for activation.

  8. Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle.

    Science.gov (United States)

    Deldicque, Louise; Atherton, Philip; Patel, Rekha; Theisen, Daniel; Nielens, Henri; Rennie, Michael J; Francaux, Marc

    2008-02-01

    To test the hypothesis that creatine supplementation would enhance the anabolic responses of muscle cell signaling and gene expression to exercise, we studied nine subjects who received either creatine or a placebo (maltodextrin) for 5 days in a double-blind fashion before undergoing muscle biopsies: at rest, immediately after exercise (10 x 10 repetitions of one-leg extension at 80% 1 repetition maximum), and 24 and 72 h later (all in the morning after fasting overnight). Creatine supplementation decreased the phosphorylation state of protein kinase B (PKB) on Thr308 at rest by 60% (P Creatine increased mRNA for collagen 1 (alpha(1)), glucose transporter-4 (GLUT-4), and myosin heavy chain I at rest by 250%, 45%, and 80%, respectively, and myosin heavy chain IIA (MHCIIA) mRNA immediately after exercise by 70% (all P creatine, mRNA for muscle atrophy F-box (MAFbx), MHCIIA, peroxisome proliferator-activated receptor gamma coactivator-1alpha, and interleukin-6 were upregulated (60-350%; P creatine supplementation do not enhance anabolic signaling but increase the expression of certain targeted genes.

  9. 强迫体位与谐振对兔血清SOD活性、MDA含量和肌肉组织中CK活性的影响*%Influence of the forced posture at resonance on activity of superoxide dismutase (SOD),level of the malondialdehyde (MDA) in the serum,and activity of creatine kinase (CK) in musclar tissue

    Institute of Scientific and Technical Information of China (English)

    左新成; 张广超; 黄昌林

    2015-01-01

    Objective To investigate the influence of activity of superoxide dismutase (SOD),level of malondialdehyde(MDA) in the serum,and activity of creatine kinase(CK) in musclar tissue in the forced posture rabbits at resonance. Methods Animals (75 New Zealand rabbits) were randomly divided into normal control group,modeling control group,4 Hz vibration group,the 5 Hz vibration group and 6 Hz vibration group,n=15 for each. Peripheral blood was taken from 5 rabbits at each group at the end of the 2 ,4 and 6 weeks separately. After the animals were killed,the psoas about 0.2 g were taken. Then the activity of the superoxide dismutase (SOD),the content of the malondialdehyde (MDA) in the serum,and the activity of creatine kinase in the homogenate were detected. Results The activity of SOD of different vibration group was less than normal control group at different time (P<0.05),and with the development of the time the activity of SOD of different group was less and less(P<0.05);the content of the MDA of different vibration group was more than normal control group at different time(P<0.05),and with the development of the time the content of the MDA of different group was more and more (P<0.05);the activity of the CK of different vibration group was more than normal control group at different time (P<0.05),and with the development of the time the activity of the CK of different group was more and more(P<0.05). Conclusion Forced posture and the resonance can cause the change of the activity of SOD, the content of the MDA in the serum and the activity of the CK in muscles of low back ,and related to time. The influence on the serum markers of muscles of resonance at the frequency of 4Hz,acceleration of 1.0g is most obvious. A negative correlation is found between the content of MDA and the activity of SOD. The extent of damage of the muscles is correlated positively with the content of the MDA.%目的:探讨强迫体位下谐振对兔血清超氧化物歧化酶(SOD)活性

  10. Characteristics of blood lactate,creatine kinase and other indicators in the fatigue recovery from negative pressure to normal pressure%负压-常压疲劳恢复过程中血乳酸、肌酸激酶等指标的特征分析

    Institute of Scientific and Technical Information of China (English)

    刘振宇; 张晓辉; 陈万

    2014-01-01

    Objective:To study the change and characteristics of blood lactate,creatine kinase and other indicators in different recovery processes under the same fatigue mode,and thus investigate the effectiveness of lower limb negative pressure - normal pressure chamber for quick recovery of physical exercise fatigue. Methods:To make the subjects exhaustive with exercise training and then respectively take 3 different ways for restoration(30 min),i. e. , lower limb negative pressure - normal pressure chamber,traditional recovery(15 min jogging and 15 min manual massage)and natural recovery(stay still for a rest). To detect changes in blood lactate,creatine kinase( CK) and blood urea nitrogen( BUN ) before and after restoration and record the subjective feeling of fatigue and heart rate of the subjects. Results:1) Changes of related indicators took place in different restorations. Immediately after restoring in chambers or the traditional way,the blood lactate was significantly different( P < 0. 05) compared with the natural recovery group,while heart rate and subjective fatigue feeling had no difference. 2)For CK changes,24 hours after restoration,compared with the natural recovery group,there was a significant difference(P < 0. 05)in the groups with chamber recovery or traditional recovery. 3)For the related indicators immediately after the restoration,there was no significant difference in heart rate and the subjective feeling of fatigue. Conclusions:1)From the blood lactate indicator,the chamber recovery after physical exercise fatigue had the best effect, followed by massage recovery,and natural recovery was the worst. 2)From the CK indicator, the chamber recovery and massage recovery in the initial period(within 1 h after training)are not as good as natural recovery. 3)The use of lower limb negative pressure - normal pressure recovery chamber for recovery can help improve the circulation of blood and lymphatic system,break down blood lactate and CK,and improve capillary

  11. Dynamic variation of creatine kinase MB isoenzymes and diagnostic value of myocardial damage in ;children with rotavirus diarrhea%轮状病毒感染患儿肌酸激酶同工酶动态变化及其对心肌损害的诊断价值

    Institute of Scientific and Technical Information of China (English)

    施学文; 陈向前; 殷铭东; 曹青

    2015-01-01

    Objective To investagate the change of creatine kinase MB isoenzymes ( CK-MB ) in children with rotavirus diarrhea and to explore the value of CK-MB/CK in the diagnosis of myocardial damage. Methods A retrospective analysis of the clinical manifestation, laboratory test data and treatment was per-formed in children with rotavirus diarrhea and high CK-MB hospitalized in department of infectious disease, Si-hong Children Hospital. We investigated the dynamic changes of CK-MB in the rotavirus diarrhea patients with and without myocardial damage. Within the non-myocardial damage group, the fluctuation of CK-MB was compared between patients with nutrition therapy and patients with conventional therapy. Receiver operating characteristic ( ROC) curve was used to explore the predictive value of CK-MB/CK for the myocardial dam-age. Results A total of 603 patients (369 males, 234 females, aged 2~48 months) with high CK-MB were enrolled in this study ( 36 cases with myocardial damage ) . There were 54. 6% of enrolled patients showing higher CK-MB and 3. 3% of patients had myocardial damage. The levels of serum CK-MB in non-myocardial damage group reached the peak on day 7 and decreased to normal in 14 days. The levels of serum CK-MB in myocardial damage group reached the peak on day 14 and maintained at fairly high level for 8 weeks and then decreased to normal . Time for CK-MB to achieve peak is different between these two groups. There was no statistical significance in the levels of serum CK-MB on day1 to day 14 between patients with or without myocar-dial protection ( P >0. 05 ) . The ROC curves were constructed with area under the ROC curves of 0. 697 (0. 611, 0. 784, 95%CI). Conclusion Intrinsic dynamics of CK-MB existed in patients with rotavirus diar-rhea. The diagnostic value of CK-MB is limited in patients with myocardial damage.%目的:探讨肌酸激酶心肌同工酶( creatine kinase MB isoenzymes, CK-MB)在轮状病毒感染中的动态变化规律,并分析CK

  12. A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS.

    Science.gov (United States)

    Yang, Yin M; Gupta, Shailesh K; Kim, Kevin J; Powers, Berit E; Cerqueira, Antonio; Wainger, Brian J; Ngo, Hien D; Rosowski, Kathryn A; Schein, Pamela A; Ackeifi, Courtney A; Arvanites, Anthony C; Davidow, Lance S; Woolf, Clifford J; Rubin, Lee L

    2013-06-06

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, characterized by motor neuron (MN) death, for which there are no truly effective treatments. Here, we describe a new small molecule survival screen carried out using MNs from both wild-type and mutant SOD1 mouse embryonic stem cells. Among the hits we found, kenpaullone had a particularly impressive ability to prolong the healthy survival of both types of MNs that can be attributed to its dual inhibition of GSK-3 and HGK kinases. Furthermore, kenpaullone also strongly improved the survival of human MNs derived from ALS-patient-induced pluripotent stem cells and was more active than either of two compounds, olesoxime and dexpramipexole, that recently failed in ALS clinical trials. Our studies demonstrate the value of a stem cell approach to drug discovery and point to a new paradigm for identification and preclinical testing of future ALS therapeutics.

  13. Inborn errors of creatine metabolism and epilepsy.

    Science.gov (United States)

    Leuzzi, Vincenzo; Mastrangelo, Mario; Battini, Roberta; Cioni, Giovanni

    2013-02-01

    Creatine metabolism disorders include guanidinoacetate methyltransferase (GAMT) deficiency, arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CT1-encoded by SLC6A8 gene) deficiency. Epilepsy is one of the main symptoms in GAMT and CT1 deficiency, whereas the occurrence of febrile convulsions in infancy is a relatively common presenting symptom in all the three above-mentioned diseases. GAMT deficiency results in a severe early onset epileptic encephalopathy with development arrest, neurologic deterioration, drug-resistant seizures, movement disorders, mental disability, and autistic-like behavior. In this disorder, epilepsy and associated abnormalities on electroencephalography (EEG) are more responsive to substitutive treatment with creatine monohydrate than to conventional antiepileptic drugs. AGAT deficiency is mainly characterized by mental retardation and severe language disorder without epilepsy. In CT1 deficiency epilepsy is generally less severe than in GAMT deficiency. All creatine disorders can be investigated through measurement of creatine metabolites in body fluids, brain proton magnetic resonance spectroscopy ((1) H-MRS), and molecular genetic techniques. Blood guanidinoacetic acid (GAA) assessment and brain H-MRS examination should be part of diagnostic workup for all patients presenting with epileptic encephalopathy of unknown origin. In girls with learning and/or intellectual disabilities with or without epilepsy, SLC6A8 gene assessment should be part of the diagnostic procedures. The aims of this review are the following: (1) to describe the electroclinical features of epilepsy occurring in inborn errors of creatine metabolism; and (2) to delineate the metabolic alterations associated with GAMT, AGAT, and CT1 deficiency and the role of a substitutive therapeutic approach on their clinical and electroencephalographic epileptic patterns. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  14. FLZ protects dopaminergic neuron through activating protein kinase B/mammalian target of rapamycin pathway and inhibiting RTP801 expression in Parkinson's disease models.

    Science.gov (United States)

    Bao, X-Q; Kong, X-C; Qian, C; Zhang, D

    2012-01-27

    The pathogenesis of Parkinson's disease is characterized by progressive degeneration of dopaminergic neurons in substantia nigra (SNpc). FLZ, a novel synthetic squamosamide derivative from a Chinese herb, has been shown to have neuroprotective effects in experimental Parkinson's disease (PD) models. However, it is still unclear whether FLZ protects against PD through regulating the function of dopaminergic system. In this study, we carried out a set of in vitro and in vivo experiments to address these questions. Oral administration of FLZ significantly improved motor dysfunction of mice challenged by MPTP. The beneficial effects of FLZ on motor behavior attributed to the elevation of dopamine level in striatum, tyrosine hydroxylase (TH)-positive cells, and TH activity in the middle brain of mouse. Mechanism study showed that treatment of FLZ increased the phosphorylation of activating protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Using LY294002 to block phosphoinositide 3-kinases (PI3K)/Akt signaling pathway prevented the phosphorylation of mTOR and attenuated the neuroprotection of FLZ in MN9D cells challenged by MPP(+). In addition, FLZ reduced the expression of RTP801, an important protein in PD, in mice and cells intoxicated by MPTP/MPP(+). Taken together, these results revealed a novel role that FLZ elevated TH expression and activity in dopaminergic neuron through activation of Akt/mTOR survival pathway and inhibition of RTP801 in MPTP/MPP(+)-induced PD models. The data also provided evidence that FLZ had potent neuroprotecive effects and might become a new promising anti-PD drug.

  15. The Regulation and Expression of the Creatine Transporter: A Brief Review of Creatine Supplementation in Humans and Animals

    Directory of Open Access Journals (Sweden)

    Greenwood Mike

    2006-06-01

    Full Text Available Abstract Creatine monohydrate has become one of the most popular ergogenic sport supplements used today. It is a nonessential dietary compound that is both endogenously synthesized and naturally ingested through diet. Creatine ingested through supplementation has been observed to be absorbed into the muscle exclusively by means of a creatine transporter, CreaT1. The major rationale of creatine supplementation is to maximize the increase within the intracellular pool of total creatine (creatine + phosphocreatine. There is much evidence indicating that creatine supplementation can improve athletic performance and cellular bioenergetics, although variability does exist. It is hypothesized that this variability is due to the process that controls both the influx and efflux of creatine across the cell membrane, and is likely due to a decrease in activity of the creatine transporter from various compounding factors. Furthermore, additional data suggests that an individual's initial biological profile may partially determine the efficacy of a creatine supplementation protocol. This brief review will examine both animal and human research in relation to the regulation and expression of the creatine transporter (CreaT. The current literature is very preliminary in regards to examining how creatine supplementation affects CreaT expression while concomitantly following a resistance training regimen. In conclusion, it is prudent that future research begin to examine CreaT expression due to creatine supplementation in humans in much the same way as in animal models.

  16. Whole body creatine and protein kinetics in healthy men and women: effects of creatine and amino acid supplementation.

    Science.gov (United States)

    Kalhan, Satish C; Gruca, Lourdes; Marczewski, Susan; Bennett, Carole; Kummitha, China

    2016-03-01

    Creatine kinetics were measured in young healthy subjects, eight males and seven females, age 20-30 years, after an overnight fast on creatine-free diet. Whole body turnover of glycine and its appearance in creatine was quantified using [1-(13)C] glycine and the rate of protein turnover was quantified using L-ring [(2)H5] phenylalanine. The creatine pool size was estimated by the dilution of a bolus [C(2)H3] creatine. Studies were repeated following a five days supplement creatine 21 g.day(-1) and following supplement amino acids 14.3 g day(-1). Creatine caused a ten-fold increase in the plasma concentration of creatine and a 50 % decrease in the concentration of guanidinoacetic acid. Plasma amino acids profile showed a significant decrease in glycine, glutamine, and taurine and a significant increase in citrulline, valine, lysine, and cysteine. There was a significant decrease in the rate of appearance of glycine, suggesting a decrease in de-novo synthesis (p = 0.006). The fractional and absolute rate of synthesis of creatine was significantly decreased by supplemental creatine. Amino acid supplement had no impact on any of the parameters. This is the first detailed analysis of creatine kinetics and the effects of creatine supplement in healthy young men and women. These methods can be applied for the analysis of creatine kinetics in different physiological states.

  17. A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells.

    Science.gov (United States)

    Land, Marianne; Rubin, Charles S

    2017-10-01

    Ca(2+)- and diacylglycerol (DAG)-activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a Caenorhabditis elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc ) and migrates along the Tc within a 17 to 25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals. Cell-specific manipulation of PKC-2 activity revealed that thermotaxis is controlled by cooperative PKC-2-mediated signaling in both AFD sensory neurons and intestinal cells. Cold-directed migration (cryophilic drive) precedes Tc tracking during thermotaxis. Analysis of temperature-directed behaviors elicited by persistent PKC-2 activation or inhibition in AFD (or intestine) disclosed that PKC-2 regulates initiation and duration of cryophilic drive. In AFD neurons, PKC-2 is a Ca(2+) sensor and signal amplifier that operates downstream from cyclic GMP-gated cation channels and distal guanylate cyclases. UNC-18, which regulates neurotransmitter and neuropeptide release from synaptic vesicles, is a critical PKC-2 effector in AFD. UNC-18 variants, created by mutating Ser(311) or Ser(322), disrupt thermotaxis and suppress PKC-2-dependent cryophilic migration. Copyright © 2017 American Society for Microbiology.

  18. Phosphatidylinositol 3-kinase/Akt signaling pathway mediates acupuncture-induced dopaminergic neuron protection and motor function improvement in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Kim, Seung-Nam; Kim, Seung-Tae; Doo, Ah-Reum; Park, Ji-Yeun; Moon, Woongjoon; Chae, Younbyoung; Yin, Chang Shik; Lee, Hyejung; Park, Hi-Joon

    2011-10-01

    It has been reported that acupuncture treatment reduced dopaminergic neuron degeneration in Parkinson's disease (PD) models. However, the mechanistic pathways underlying, such neuroprotection, are poorly understood. Here, we investigated the effects and the underlying mechanism of acupuncture in a mouse model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). First, we observed that MPTP-induced impairment of Akt activation, but not MPTP-induced c-Jun activation, was effectively restored by acupuncture treatment in the substantia nigra. Furthermore, we demonstrated for the first time that the brain-specific blockade of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, by intranasal administration of LY294002, a specific inhibitor of PI3K/Akt signaling pathway, significantly blocked acupuncture-induced dopaminergic neuron protection and motor function improvement. Our results provide evidence that PI3K/Akt signaling pathway may play a central role in the mechanism underlying acupuncture-induced benefits in Parkinsonian mice.

  19. Mixed lineage kinase phosphorylates transcription factor E47 and inhibits TrkB expression to link neuronal death and survival pathways.

    Science.gov (United States)

    Pedraza, Neus; Rafel, Marta; Navarro, Isis; Encinas, Mario; Aldea, Martí; Gallego, Carme

    2009-11-20

    E47 is a basic helix-loop-helix transcription factor involved in neuronal differentiation and survival. We had previously shown that the basic helix-loop-helix protein E47 binds to E-box sequences within the promoter of the TrkB gene and activates its transcription. Proper expression of the TrkB receptor plays a key role in development and function of the vertebrate nervous system, and altered levels of TrkB have been associated with important human diseases. Here we show that E47 interacts with MLK2, a mixed lineage kinase (MLK) involved in JNK-mediated activation of programmed cell death. MLK2 enhances phosphorylation of the AD2 activation domain of E47 in vivo in a JNK-independent manner and phosphorylates in vitro defined serine and threonine residues within a loop-helix structure of AD2 that also contains a putative MLK docking site. Although these residues are essential for MLK2-mediated inactivation of E47, inhibition of MLKs by CEP11004 causes up-regulation of TrkB at a transcriptional level in cerebellar granule neurons and differentiating neuroblastoma cells. These findings allow us to propose a novel mechanism by which MLK regulates TrkB expression through phosphorylation of an activation domain of E47. This molecular link would explain why MLK inhibitors not only prevent activation of cell death processes but also enhance cell survival signaling as a key aspect of their neuroprotective potential.

  20. Creatine monohydrate increases bone mineral density in young Sprague-Dawley rats.

    Science.gov (United States)

    Antolic, Anamaria; Roy, Brian D; Tarnopolsky, Mark A; Zernicke, Ronald F; Wohl, Gregory R; Shaughnessy, Stephen G; Bourgeois, Jacqueline M

    2007-05-01

    Creatine kinase, found in osteoblasts, is an enzyme that is upregulated in response to interventions that enhance bone mass accretion. Creatine monohydrate supplementation can increase fat-free mass in young healthy men and women and can reduce markers of bone breakdown in boys with Duchenne muscular dystrophy. The objective of this study was to determine the influence of supplementation with creatine monohydrate on bone structure and function in growing rats, to establish a therapeutic model. Creatine monohydrate (2% w.w.) (CR; N = 16) or standard rat chow (CON; N = 16) was fed to Sprague-Dawley rats beginning at 5 wk of age, for 8 wk. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy x-ray absorptiometry at the beginning and end of the protocol. The rats were sacrificed, and one femur was removed for the determination of mechanical properties. The CR-treated rats showed greater lumbar BMD and femoral bending load at failure compared with the CON rats (P properties and its effects in disorders associated with bone loss.

  1. Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons.

    Science.gov (United States)

    Ritter, David M; Ho, Cojen; O'Leary, Michael E; Covarrubias, Manuel

    2012-01-01

    Fast inactivation of heterologously expressed Kv3.4 channels is dramatically slowed upon phosphorylation of the channel's N-terminal (N-type) inactivation gate by protein kinase C (PKC). However, the presence and physiological importance of this exquisite modulation in excitable tissues were unknown. Here, we employed minimally invasive cell-attached patch-clamping, single-cell qPCR and specific siRNAs to unambiguously demonstrate that fast-inactivating Kv3.4 channels underlie a robust high voltage-activated A-type K(+) current (I(AHV)) in nociceptive dorsal root ganglion neurons from 7-day-old rats. We also show that PKC activation with phorbol 12,13-dibutyrate (PDBu) causes a 4-fold slowing of Kv3.4 channel inactivation and, consequently, accelerates the repolarization of the action potential (AP) by 22%, which shortens the AP duration by 14%. G-protein coupled receptor (GPCR) agonists eliminate I(AHV) fast inactivation in a membrane-delimited manner, suggesting a Kv3.4 channel signalling complex. Preincubation of the neurons with the PKC inhibitor bisindolylmaleimide II inhibits the effect of GPCR agonists and PDBu. Furthermore, activation of PKC via GPCR agonists recapitulates the effects of PDBu on the AP. Finally, transfection of the neurons with Kv3.4 siRNA prolongs the AP by 25% and abolishes the GPCR agonist-induced acceleration of the AP repolarization. These results show that Kv3.4 channels help shape the repolarization of the nociceptor AP, and that modulation of Kv3.4 channel N-type inactivation by PKC regulates AP repolarization and duration. We propose that the dramatic modulation of I(AHV) fast inactivation by PKC represents a novel mechanism of neural plasticity with potentially significant implications in the transition from acute to chronic pain.

  2. Erythropoietin Rescues Primary Rat Cortical Neurons by Altering the Nrf2:Bach1 Ratio: Roles of Extracellular Signal-Regulated Kinase 1/2.

    Science.gov (United States)

    Zhang, Li-Min; Zhang, Dong-Xue; Zhao, Xiao-Chun; Sun, Wenbo

    2017-01-12

    While inhalation anesthetics are indispensable, and generally considered safe and effective, there is growing concern about the selective neurotoxicity of these agents, especially sevoflurane. Erythropoetin (EPO)-induced protection against sevoflurane-induced neuronal death is an effective intervention, but the underlying mechanism is poorly understood. Extracellular signal-related kinases (Erk) 1/2 plays a pivotal role in cell growth and proliferation. Alteration of the nuclear factor erythroid 2-related factor (Nrf2)/BTB-to-CNC homology 1 (Bach1) ratio by Erk1/2 ameliorates the oxidative stress which occurs in human macrophages. Primary cortical neuron cultures exposed to sevoflurane were assessed for Nrf2, Bach1, total Erk1/2, and phosphorylated Erk1/2 with the following: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; propidium iodide uptake; lactate dehydrogenase; malondialdehyde (MDA); superoxide dismutase (SOD); and Western blot. Sevoflurane exposure increased cell death, injury, and MDA (n = 9, P < 0.05), but decreased cell viability and the Nrf2:Bach1 ratio (n = 9, P < 0.05) and down-regulated SOD (n = 9, P < 0.05), while EPO partially rescued the neurotoxicity induced by sevoflurane (n = 9, P < 0.05). Inhibition of Erk1/2 phosphorylation via PD98059 reversed the protective effect of EPO (n = 9, P < 0.05). Thus, protection of EPO markedly attenuated death of neurons exposed to sevoflurane by altering the Nrf2:Bach1 ratio mediated by phosphorylation and activation of Erk1/2.

  3. Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shang-Der, E-mail: chensd@adm.cgmh.org.tw [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Lin, Tsu-Kung [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Yang, Ding-I. [Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei, Taiwan (China); Lee, Su-Ying [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Shaw, Fu-Zen [Department of Psychology, National Cheng Kung University, Tainan, Taiwan (China); Liou, Chia-Wei [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Chuang, Yao-Chung, E-mail: ycchuang@adm.cgmh.org.tw [Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China); Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan (China)

    2015-05-01

    Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616. - Highlights: • Transient global ischemia increases expression of PINK1 and p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA decreases PINK1 expression but increases p-Drp1 at Ser616 in hippocampal CA1 subfield. • PINK1-siRNA augments oxidative stress and neuronal damage in hippocampal CA1 subfield.

  4. Creatine and the Male Adolescent Athlete

    Science.gov (United States)

    Schumaker, Shauna; Eyers, Christina; Cappaert, Thomas

    2012-01-01

    As the level of competition in youth sports increases, so does athletes' vulnerability to experimenting with performance-enhancing aids (PEAs) at alarmingly young ages. One of the more commonly used PEAs is a supplement called creatine, which has the ability to generate muscular energy, allowing athletes to train at higher intensities for longer…

  5. Activation of c-Jun N-terminal kinase 1/2 regulated by nitric oxide is associated with neuronal survival in hippocampal neurons in a rat model of ischemia

    Institute of Scientific and Technical Information of China (English)

    ZENG Xian-wei; LI Ming-wei; PAN Jing; JI Tai-ling; YANG Bin; ZHANG Bo; WANG Xiao-qiang

    2011-01-01

    Background C-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in cerebral ischemia.Although the mechanistic basis for this activation of JNK1/2 is uncertain,oxidative stress may play a role.The purpose of this study was to investigate whether the activation of JNK1/2 is associated with the production of endogenous nitric oxide (NO).Methods Ischemia and reperfusion (I/R) was induced by cerebral four-vessel occlusion.Sprague-Dawley (SD) rats were divided into 6 groups:sham group,I/R group,neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole,7-NI)given group,inducible nitric oxide synthase (iNOS) inhibitor (2-amino-5,6-dihydro-methylthiazine,AMT) given group,sodium chloride control group,and 1% dimethyl sulfoxide (DMSO) control group.The levels of protein expression and phospho-JNK1/2 were detected by Western blotting and the survival hippocampus neurons in CA1 zone were observed by cresyl violet staining.Results The study illustrated two peaks of JNK1/2 activation occurred at 30 minutes and 3 days during reperfusion.7-NI inhibited JNK1/2 activation during the early reperfusion,whereas AMT preferably attenuated JNK1/2 activation during the later reperfusion.Administration of 7-NI and AMT can decrease I/R-induced neuronal loss in hippocampal CA1 region.Conclusion JNK1/2 activation is associated with endogenous NO in response to ischemic insult.

  6. Neuronal calcium/calmodulin-dependent protein kinase II mediates nicotine reward in the conditioned place preference test in mice.

    Science.gov (United States)

    Jackson, Kia J; Muldoon, Pretal P; Walters, Carrie; Damaj, Mohamad Imad

    2016-02-01

    Several recent studies have indicated the involvement of calcium-dependent mechanisms, in particular the abundant calcium-activated kinase, calcium/calmodulin-dependent kinase II (CaMKII), in behaviors associated with nicotine dependence in mice. Behavioral and biochemical studies have shown that CaMKII is involved in acute and chronic nicotine behaviors and nicotine withdrawal; however, evidence of a role for CaMKII in nicotine reward is lacking. Thus, the goal of the current study was to examine the role of CaMKII in nicotine reward. Using pharmacological and genetic tools, we tested nicotine conditioned place preference (CPP) in C57Bl/6 mice after administration of CaMKII antagonists and in α-CaMKII wild-type (+/+) and heterozygote (±) mice. CaMKII antagonists blocked expression of nicotine CPP, and the preference score was significantly reduced in α-CaMKII ± mice compared with their +/+ counterparts. Further, we assessed CaMKII activity in the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex, and hippocampus after nicotine CPP and found significant increases in CaMKII activity in the mouse VTA and NAc that were blocked by CaMKII antagonists. The findings from this study show that CaMKII mediates nicotine reward and suggest that increases in CaMKII activity in the VTA and NAc are relevant to nicotine reward behaviors.

  7. Acute Changes in Creatine Kinase Serum Levels in Adults Submitted a Static Flexibilizing and Maximal Strength Test Modificaciones agudas de los niveles séricos de creatina quinasa en adultos jóvenes sometidos al trabajo de flexibilidad estática y de fuerza máxima

    Directory of Open Access Journals (Sweden)

    L. Conte

    2010-09-01

    Full Text Available

     

    ABSTRACT

    Strength and flexibility, important components of a training and their maximal values are obtained through specific tests. However, little information about the damage effect in a skeletal muscle is known. The aim was to verify a serum CK changes 24 h after a lengthening and static flexibilizing routine and a maximal dynamic strength tests. The sample, was by 14 subjects (man and women, 28 ± 6 yr., control group (CG N = 7 and experimental group (EG N = 4 that was submitted a lengthening routine (EG-LG, a static flexibilizing routine (EG-FLEX and a 1-RM test (EG-1-RM. The anthropometrics were obtained by digital scale with stadiometer. The blood samples were obtained using the IFCC method with reference values 26-155 U/L. The De Lorme and Watkins technique was used to access maximal dynamic strength through bench press and leg press. The static flexibilizing routine consisted in three 20 seconds sets until the point of maximal discomfort. The lengthening was done in normal movement amplitude during 6 seconds. In analysis inter groups was a significant difference (p < .05 in the values of GE-1RM (D = 118,7 U/L, p= .02 when compared to the GC. We concluded that only maximal strength dynamic test was capable to raise the CK serum levels 24 h after exercise
    Key Words:
    Lengthening, Static Flexibilizing, 1-RM, Creatine Kinase

     

    RESUMEN

    La fuerza y flexibilidad, muy importantes en entrenamiento, obtienen sus valores máximos a través de test específicos. Se sabe poco sobre sus efectos perjudiciales en el aparato músculo tendinoso. El objetivo fue verificar las modificaciones séricas de CK 24h después de estiramientos, flexibilidad estática y

  8. The influence of sevoflurane inhalation on serum troponin Ⅰ and MB isoenzyme of creatine kinase in non-cyanosis congenital heart disease infants undergoing cardiac surgery%吸入七氟烷麻醉对非发绀型先天性心脏病患儿心脏手术围术期心肌损伤的影响

    Institute of Scientific and Technical Information of China (English)

    吴琼; 董秀华; 卿恩明; 卢家凯

    2012-01-01

    目的:观察吸入七氟烷麻醉对非发绀型先天性心脏病(先心病)患儿心脏手术围术期血浆心肌坏死标记物肌钙蛋白Ⅰ(TnⅠ)及肌酸激酶同工酶(CKMB)的影响.方法:择期行心脏手术的非发绀型先心病患儿60例,随机分为七氟烷组(S组)及氯胺酮组(K组),分别在术中实施七氟烷-芬太尼或氯胺酮-芬太尼麻醉,观察术中的血流动力学及围术期TnⅠ、CKMB、血糖(Glu)及乳酸(Lac)水平变化.结果:S组与K组比较,S组平均动脉压(MAP)在诱导后、切皮及术毕均比K组高(P<0.05),S组HR在术毕比K组低(P<0.05),S组在术后4h及24 hTnⅠ水平显著低于K组(P<0.05),CKMB在术后24h显著低于K组水平(P<0.05),2组Glu及Lac浓度在各时点差异无统计学意义(P>0.05).结论:吸入七氟烷麻醉在非发绀型先心病患儿心脏手术围术期,可以降低血浆TnⅠ及CKMB水平,对患儿心肌可能起到保护作用.%Objective:To observe the effect of sevoflurane inhalation anesthesia on myocardial injury bi-omarker Troponin I (Tnl) and MB isoenzyme of creatine kinase (CKMB) in non-cyanosis congenital heart disease infants undergoing cardiac surgery. Methods: Sixty non-cyanosis congenital heart disease infants undergoing selective cardiac surgery were recruited for present study. Patients were randomly assigned to sevoflurane group (Group S) and ketamine group (Group K) and received sevoflurane inhalation or ketamine injection for anesthetic induction and maintenance respectively. Intraoperative hemodynamics were recorded and perioperative serum level of Tnl, CKMB, blood glucose and lactate were measured. Results; Mean artery pressure increased significantly in Group S compared with Group K at post-induction, skin incision and at the end of the surgery(P < 0. 05 ) , Heart rate in Group S was significantly lower than that of in Group K (P < 0.05 ). The serum Tnl level in group S was significantly lower than that of Group K at postoperative 4h and 24 h

  9. Creatine loading elevates the intracellular phosphorylation potential and alters adaptive responses of rat fast-twitch muscle to chronic low-frequency stimulation.

    Science.gov (United States)

    Putman, Charles T; Gallo, Maria; Martins, Karen J B; MacLean, Ian M; Jendral, Michelle J; Gordon, Tessa; Syrotuik, Daniel G; Dixon, Walter T

    2015-07-01

    This study tested the hypothesis that elevating the intracellular phosphorylation potential (IPP = [ATP]/[ADP]free) within rat fast-twitch tibialis anterior muscles by creatine (Cr) loading would prevent fast-to-slow fibre transitions induced by chronic low-frequency electrical stimulation (CLFS, 10 Hz, 12 h/day). Creatine-control and creatine-CLFS groups drank a solution of 1% Cr + 5% dextrose, ad libitum, for 10 days before and during 10 days of CLFS; dextrose-control and dextrose-CLFS groups drank 5% dextrose. Cr loading increased total Cr (P creatine-CLFS than in dextrose-CLFS. Higher IPP was confirmed by a 58% reduction in phospho-AMP-activated protein kinase α (Thr172) (P creatine-CLFS, MyHC-I and MyHC-IIa mRNA were unchanged and MyHC-IIb mRNA decreased by 75% (P creatine-CLFS, but reciprocal reductions in glycolytic reference enzymes occurred only in dextrose-CLFS (P creatine-CLFS coincided with prolonged time to peak tension and half-rise time (P < 0.01). These results highlight the IPP as an important physiological regulator of muscle fibre plasticity and demonstrate that training-induced changes typically associated with improvements in muscular endurance or increased power output are not mutually exclusive in Cr-loaded muscles.

  10. AMPK and substrate availability regulate creatine transport in cultured cardiomyocytes.

    Science.gov (United States)

    Darrabie, Marcus D; Arciniegas, Antonio Jose Luis; Mishra, Rajashree; Bowles, Dawn E; Jacobs, Danny O; Santacruz, Lucia

    2011-05-01

    Profound alterations in myocellular creatine and phosphocreatine levels are observed during human heart failure. To maintain its intracellular creatine stores, cardiomyocytes depend upon a cell membrane creatine transporter whose regulation is not clearly understood. Creatine transport capacity in the intact heart is modulated by substrate availability, and it is reduced in the failing myocardium, likely adding to the energy imbalance that characterizes heart failure. AMPK, a key regulator of cellular energy homeostasis, acts by switching off energy-consuming pathways in favor of processes that generate energy. Our objective was to determine the effects of substrate availability and AMPK activation on creatine transport in cardiomyocytes. We studied creatine transport in rat neonatal cardiomyocytes and HL-1 cardiac cells expressing the human creatine transporter cultured in the presence of varying creatine concentrations and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR). Transport was enhanced in cardiomyocytes following incubation in creatine-depleted medium or AICAR. The changes in transport were due to alterations in V(max) that correlated with changes in total and cell surface creatine transporter protein content. Our results suggest a positive role for AMPK in creatine transport modulation for cardiomyocytes in culture.

  11. Hindbrain A2 noradrenergic neuron adenosine 5'-monophosphate-activated protein kinase activation, upstream kinase/phosphorylase protein expression, and receptivity to hormone and fuel reporters of short-term food deprivation are regulated by estradiol.

    Science.gov (United States)

    Briski, Karen P; Alenazi, Fahaad S H; Shakya, Manita; Sylvester, Paul W

    2017-07-01

    Estradiol (E) mitigates acute and postacute adverse effects of 12 hr-food deprivation (FD) on energy balance. Hindbrain 5'-monophosphate-activated protein kinase (AMPK) regulates hyperphagic and hypothalamic metabolic neuropeptide and norepinephrine responses to FD in an E-dependent manner. Energy-state information from AMPK-expressing hindbrain A2 noradrenergic neurons shapes neural responses to metabolic imbalance. Here we investigate the hypothesis that FD causes divergent changes in A2 AMPK activity in E- vs. oil (O)-implanted ovariectomized female rats, alongside dissimilar adjustments in circulating metabolic fuel (glucose, free fatty acids [FFA]) and energy deficit-sensitive hormone (corticosterone, glucagon, leptin) levels. FD decreased blood glucose in oil (O)- but not E-implanted ovariectomized female rats and elevated and reduced glucagon levels in O and E, respectively. FD decreased circulating leptin in O and E, but increased corticosterone and FFA concentrations in E only. Western blot analysis of laser-microdissected A2 neurons showed that glucocorticoid receptor type II and very-long-chain acyl-CoA synthetase 3 protein profiles were amplified in FD/E vs. FD/O. A2 total AMPK protein was elevated without change in activity in FD/O, whereas FD/E exhibited increased AMPK activation along with decreased upstream phosphatase expression. The catecholamine biosynthetic enzyme dopamine-β-hydroxylase (DβH) was increased in FD/O but not FD/E A2 cells. The data show discordance between A2 AMPK activation and glycemic responses to FD; sensor activity was refractory to glucose decrements in FD/O but augmented in FD/E despite stabilized glucose and elevated FFA levels. E-dependent amplification of AMPK activity may reflect adaptive conversion to fatty acid oxidation and/or glucocorticoid stimulation. FD augmentation of A2 DβH protein profiles in FD/O but not FD/E animals suggests that FD may correspondingly regulate NE synthesis vs. metabolism/release in the

  12. Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

    Science.gov (United States)

    Putney, S; Herlihy, W; Royal, N; Pang, H; Aposhian, H V; Pickering, L; Belagaje, R; Biemann, K; Page, D; Kuby, S

    1984-12-10

    A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

  13. EFFECTS OF COMBINED CREATINE PLUS FENUGREEK EXTRACT VS. CREATINE PLUS CARBOHYDRATE SUPPLEMENTATION ON RESISTANCE TRAINING ADAPTATIONS

    Directory of Open Access Journals (Sweden)

    Cliffa Foster

    2011-06-01

    Full Text Available The purpose of this study was to evaluate the effects of combined creatine and fenugreek extract supplementation on strength and body composition. Forty- seven resistance trained men were matched according to body weight to ingest either 70 g of a dextrose placebo (PL, 5 g creatine/70 g of dextrose (CRD or 3.5 g creatine/900 mg fenugreek extract (CRF and participate in a 4-d/wk periodized resistance-training program for 8-weeks. At 0, 4, and 8-weeks, subjects were tested on body composition, muscular strength and endurance, and anaerobic capacity. Statistical analyses utilized a separate 3X3 (condition [PL vs. CRD vs. CRF] x time [T1 vs. T2 vs. T3] ANOVAs with repeated measures for all criterion variables (p 0.05 were observed for any measures of body composition. CRF group showed significant increases in lean mass at T2 (p = 0.001 and T3 (p = 0.001. Bench press 1RM increased in PL group (p = 0.050 from T1-T3 and in CRD from T1-T2 (p = 0. 001 while remaining significant at T3 (p 0.05. In conclusion, creatine plus fenugreek extract supplementation had a significant impact on upper body strength and body composition as effectively as the combination of 5g of creatine with 70g of dextrose. Thus, the use of fenugreek with creatine supplementation may be an effective means for enhancing creatine uptake while eliminating the need for excessive amounts of simple carbohydrates

  14. Protein kinase A-dependent Neuronal Nitric Oxide Synthase Activation Mediates the Enhancement of Baroreflex Response by Adrenomedullin in the Nucleus Tractus Solitarii of Rats

    Directory of Open Access Journals (Sweden)

    Ho I-Chun

    2011-05-01

    Full Text Available Abstract Background Adrenomedullin (ADM exerts its biological functions through the receptor-mediated enzymatic mechanisms that involve protein kinase A (PKA, or neuronal nitric oxide synthase (nNOS. We previously demonstrated that the receptor-mediated cAMP/PKA pathway involves in ADM-enhanced baroreceptor reflex (BRR response. It remains unclear whether ADM may enhance BRR response via activation of nNOS-dependent mechanism in the nucleus tractus solitarii (NTS. Methods Intravenous injection of phenylephrine was administered to evoke the BRR before and at 10, 30, and 60 min after microinjection of the test agents into NTS of Sprague-Dawley rats. Western blotting analysis was used to measure the level and phosphorylation of proteins that involved in BRR-enhancing effects of ADM (0.2 pmol in NTS. The colocalization of PKA and nNOS was examined by immunohistochemical staining and observed with a laser confocal microscope. Results We found that ADM-induced enhancement of BRR response was blunted by microinjection of NPLA or Rp-8-Br-cGMP, a selective inhibitor of nNOS or protein kinase G (PKG respectively, into NTS. Western blot analysis further revealed that ADM induced an increase in the protein level of PKG-I which could be attenuated by co-microinjection with the ADM receptor antagonist ADM22-52 or NPLA. Moreover, we observed an increase in phosphorylation at Ser1416 of nNOS at 10, 30, and 60 min after intra-NTS administration of ADM. As such, nNOS/PKG signaling may also account for the enhancing effect of ADM on BRR response. Interestingly, biochemical evidence further showed that ADM-induced increase of nNOS phosphorylation was prevented by co-microinjection with Rp-8-Br-cAMP, a PKA inhibitor. The possibility of PKA-dependent nNOS activation was substantiated by immunohistochemical demonstration of co-localization of PKA and nNOS in putative NTS neurons. Conclusions The novel finding of this study is that the signal transduction cascade that

  15. [Creatine: the nutritional supplement for exercise - current concepts].

    Science.gov (United States)

    Mendes, Renata Rebello; Tirapegui, Julio

    2002-06-01

    Creatine, a natural nutrient found in animal foods, is alleged to be an effective nutritional ergogenic aid to enhance sport or exercise performance. It may be formed in kidney and liver from arginina and glicina. Creatine may be delivered to the muscle, where it may combine readily with phosphate to form creatine phosphate, a high-energy phosphagen in the ATP-CP system, and is stored. The ATP-CP energy system is important for rapid energy production, such as in speed and power events. Approximately 120 g of creatine is found in a 70 kg male, 95% in the skeletal muscle. Total creatine exists in muscle as both free creatine (40%) and phosphocreatine (60%). It is only recently that a concerted effort has been undertaken to investigate its potential ergogenic effect relative to sport or exercise performance. It does appear that oral creatine monohydrate may increase muscle total creatine, including both free and phosphocreatine. Many, but not all studies suggest that creatine supplementation may enhance performance in high intensity, short-term exercise task that are dependent primarily on the ATP-CP energy system, particularly on laboratory test involving repeated exercise bouts with limited recovery time between repetitions. Short-term creatine supplementation appears to increase body mass, although the initial increase is most likely water associated with the osmotic effect of increased intramuscular total creatine. Chronic creatine supplementation in conjunction with physical training involving resistance exercise may increase muscle mass. However, confirmatory research data are needed. Creatine supplementation up to 8 weeks, with high doses, has not been associated with major health risks; with low doses, it was demonstrated that in 5 years period supplementation, there are no adverse effects. The decision to use creatine as a mean to enhance sport performance is left to the description to the individual athlete.

  16. 2,5-己二酮染毒大鼠血清肌酸激酶、乳酸脱氢酶活性及髓鞘碱性蛋白含量的变化%Changes of the activities of creatine kinase, lactate dehydrogenates and the levels of myelin protein in HD-treated rats

    Institute of Scientific and Technical Information of China (English)

    董华; 朱明星; 谢克勤; 宋福永

    2011-01-01

    目的 研究2,5-己二酮染毒大鼠血清中肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactate dehydrogenates,LDH)活性及髓鞘碱性蛋白含量(myelin basic protein,MBP)的变化,探讨它们作为正己烷中毒性周围神经病生物标志物的可能性.方法 Wistar雄性大鼠48只,随机分为对照组、低剂量染毒组和高剂量染毒组,每组16只.对照组给予生理盐水腹腔注射,低剂量和高剂量染毒组分别给予200和400 mg/kg 2,5-己二酮(2,5-hexanedione,HD)腹腔注射,连续6周.观察动物体重、神经行为学指标变化,实验结束后取腓肠肌做病理检查,取坐骨神经做电镜观察,测定血清CK、LDH活性和MBP含量.结果 HD染毒6周后,染毒大鼠出现步态异常,腓肠肌病理提示神经源性肌肉萎缩,坐骨神经电镜结果显示轴突变性.与对照组相比,200和400 mg/kg染毒组大鼠血清CK活性分别下降19.72%和54.37%,差异有统计学意义(P<0.05);与对照组相比,400 mg/kg染毒组大鼠血清MBP含量增加34.82%,差异有统计学意义(P<0.05);而LDH活性变化无统计学意义(P>0.05).结论 2,5-HD中毒性周围神经病大鼠血清CK活性降低、MBP含量升高,它们有可能成为正已烷中毒性周围神经损害的早期生物标志物.%Objective To investigate changes of the activities of crestine kinase(CK) ,lactate dehydrogenates(LDH) and the level of myelin protein (MBP)in HD-treated rats for seeking potential biomarkers of peripheral nerve injury. Methods Totally 48 healthWistarrats were randomly divided into control group, low and high doses of 2, S-hexanedione (HD) groups. The control group was injected physiological saline; 2,5-HD groups were potentially injected 2,5-HD with the dose of 200 mg/kg,400 mg/kg for one time per day,5 days per week, respectively. All three groups had been treated five times per week for six weeks. Body weight and gait score were measured per week. After the experiment gastrocnemius muscles and

  17. Protein kinase C gamma interneurons in the rat medullary dorsal horn: distribution and synaptic inputs to these neurons, and subcellular localization of the enzyme.

    Science.gov (United States)

    Peirs, Cédric; Patil, Sudarshan; Bouali-Benazzouz, Rabia; Artola, Alain; Landry, Marc; Dallel, Radhouane

    2014-02-01

    The γ isoform of protein kinase C (PKCγ), which is concentrated in interneurons in the inner part of lamina II (IIi ) of the dorsal horn, has been implicated in the expression of tactile allodynia. Lamina IIi PKCγ interneurons were shown to be activated by tactile inputs and to participate in local circuits through which these inputs can reach lamina I, nociceptive output neurons. That such local circuits are gated by glycinergic inhibition and that A- and C-fibers low threshold mechanoreceptors (LTMRs) terminate in lamina IIi raise the general issue of synaptic inputs to lamina IIi PKCγ interneurons. Combining light and electron microscopic immunochemistry in the rat spinal trigeminal nucleus, we show that PKCγ-immunoreactivity is mostly restricted to interneurons in lamina IIi of the medullary dorsal horn, where they constitute 1/3 of total neurons. The majority of synapses on PKCγ-immunoreactive interneurons are asymmetric (likely excitatory). PKCγ-immunoreactive interneurons appear to receive exclusively myelinated primary afferents in type II synaptic glomeruli. Neither large dense core vesicle terminals nor type I synaptic glomeruli, assumed to be the endings of unmyelinated nociceptive terminals, were found on these interneurons. Moreover, there is no vesicular glutamate transporter 3-immunoreactive bouton, specific to C-LTMRs, on PKCγ-immunoreactive interneurons. PKCγ-immunoreactive interneurons contain GABAA ergic and glycinergic receptors. At the subcellular level, PKCγ-immunoreactivity is mostly concentrated on plasma membranes, close to, but not within, postsynaptic densities. That only myelinated primary afferents were found to contact PKCγ-immunoreactive interneurons suggests that myelinated, but not unmyelinated, LTMRs play a critical role in the expression of mechanical allodynia.

  18. Adenosine Monophosphate-Activated Protein Kinase Abates Hyperglycaemia-Induced Neuronal Injury in Experimental Models of Diabetic Neuropathy: Effects on Mitochondrial Biogenesis, Autophagy and Neuroinflammation.

    Science.gov (United States)

    Yerra, Veera Ganesh; Kumar, Ashutosh

    2017-04-01

    Impaired adenosine monophosphate kinase (AMPK) signalling under hyperglycaemic conditions is known to cause mitochondrial dysfunction in diabetic sensory neurons. Facilitation of AMPK signalling is previously reported to ameliorate inflammation and induce autophagic response in various complications related to diabetes. The present study assesses the role of AMPK activation on mitochondrial biogenesis, autophagy and neuroinflammation in experimental diabetic neuropathy (DN) using an AMPK activator (A769662). A769662 (15 and 30 mg/kg, i.p) was administered to Sprague-Dawley rats (250-270 g) for 2 weeks after 6 weeks of streptozotocin (STZ) injection (55 mg/kg, i.p.). Behavioural parameters (mechanical/thermal hyperalgesia) and functional characteristics (motor/sensory nerve conduction velocities (MNCV and SNCV) and sciatic nerve blood flow (NBF)) were assessed. For in vitro studies, Neuro2a (N2A) cells were incubated with 25 mM glucose to simulate high glucose condition and then studied for mitochondrial dysfunction and protein expression changes. STZ administration resulted in significant hyperglycaemia (>250 mg/dl) in rats. A769662 treatment significantly improved mechanical/thermal hyperalgesia threshold and enhanced MNCV, SNCV and NBF in diabetic animals. A769662 exposure normalised the mitochondrial superoxide production, membrane depolarisation and markedly increased neurite outgrowth of N2A cells. Further, AMPK activation also abolished the NF-κB-mediated neuroinflammation. A769662 treatment increased Thr-172 phosphorylation of AMPK results in stimulated PGC-1α-directed mitochondrial biogenesis and autophagy induction. Our study supports that compromised AMPK signalling in hyperglycaemic conditions causes defective mitochondrial biogenesis ultimately leading to neuronal dysfunction and associated deficits in DN and activation of AMPK can be developed as an attractive therapeutic strategy for the management of DN.

  19. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

    Science.gov (United States)

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help

  20. Methylene blue induces macroautophagy through 5′ adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation

    Science.gov (United States)

    Xie, Luokun; Li, Wenjun; Winters, Ali; Yuan, Fang; Jin, Kunlin; Yang, Shaohua

    2013-01-01

    Methylene blue has been shown to be neuroprotective in multiple experimental neurodegenerative disease models. However, the mechanisms underlying the neuroprotective effects have not been fully elucidated. Previous studies have shown that macroautophagy has multiple beneficial roles for maintaining normal cellular homeostasis and that induction of macroautophagy after myocardial ischemia is protective. In the present study we demonstrated that methylene blue could protect HT22 hippocampal cell death induced by serum deprivation, companied by induction of macroautophagy. We also found that methylene blue-mediated neuroprotection was abolished by macroautophagy inhibition. Interestingly, 5′ adenosine monophosphate-activated protein kinase (AMPK) signaling, but not inhibition of mammalian target of rapamycin signaling, was activated at 12 and 24 h after methylene blue treatment in a dose-dependent manner. Methylene blue-induced macroautophagy was blocked by AMPK inhibitor. Consistent with in vitro data, macroautophagy was induced in the cortex and hippocampus of mouse brains treated with methylene blue. Our findings suggest that methylene blue-induced neuroprotection is mediated, at least in part, by macroautophagy though activation of AMPK signaling. PMID:23653592

  1. Methylene blue induces macroautophagy through 5' adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation.

    Science.gov (United States)

    Xie, Luokun; Li, Wenjun; Winters, Ali; Yuan, Fang; Jin, Kunlin; Yang, Shaohua

    2013-01-01

    Methylene blue has been shown to be neuroprotective in multiple experimental neurodegenerative disease models. However, the mechanisms underlying the neuroprotective effects have not been fully elucidated. Previous studies have shown that macroautophagy has multiple beneficial roles for maintaining normal cellular homeostasis and that induction of macroautophagy after myocardial ischemia is protective. In the present study we demonstrated that methylene blue could protect HT22 hippocampal cell death induced by serum deprivation, companied by induction of macroautophagy. We also found that methylene blue-mediated neuroprotection was abolished by macroautophagy inhibition. Interestingly, 5' adenosine monophosphate-activated protein kinase (AMPK) signaling, but not inhibition of mammalian target of rapamycin signaling, was activated at 12 and 24 h after methylene blue treatment in a dose-dependent manner. Methylene blue-induced macroautophagy was blocked by AMPK inhibitor. Consistent with in vitro data, macroautophagy was induced in the cortex and hippocampus of mouse brains treated with methylene blue. Our findings suggest that methylene blue-induced neuroprotection is mediated, at least in part, by macroautophagy though activation of AMPK signaling.

  2. Fibroblast Growth Factor Receptor-2 Contributes to the Basic Fibroblast Growth Factor-Induced Neuronal Differentiation in Canine Bone Marrow Stromal Cells via Phosphoinositide 3-Kinase/Akt Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Rei Nakano

    Full Text Available Bone marrow stromal cells (BMSCs are considered as candidates for regenerative therapy and a useful model for studying neuronal differentiation. The role of basic fibroblast growth factor (bFGF in neuronal differentiation has been previously studied; however, the signaling pathway involved in this process remains poorly understood. In this study, we investigated the signaling pathway in the bFGF-induced neuronal differentiation of canine BMSCs. bFGF induced the mRNA expression of the neuron marker, microtubule associated protein-2 (MAP2 and the neuron-like morphological change in canine BMSCs. In the presence of inhibitors of fibroblast growth factor receptors (FGFR, phosphatidylinositol 3-kinase (PI3K and Akt, i.e., SU5402, LY294002, and MK2206, respectively, bFGF failed to induce the MAP2 mRNA expression and the neuron-like morphological change. bFGF induced Akt phosphorylation, but it was attenuated by the FGFR inhibitor SU5402 and the PI3K inhibitor LY294002. In canine BMSCs, expression of FGFR-1 and FGFR-2 was confirmed, but only FGFR-2 activation was detected by cross-linking and immunoprecipitation analysis. Small interfering RNA-mediated knockdown of FGFR-2 in canine BMSCs resulted in the attenuation of bFGF-induced Akt phosphorylation. These results suggest that the FGFR-2/PI3K/Akt signaling pathway is involved in the bFGF-induced neuronal differentiation of canine BMSCs.

  3. 肌酸激酶及CT血管造影检查评估肠系膜上动脉栓塞的短期预后%Creatine kinase and computed tomography angiography to evaluate short-term prognosis of patients with superior mesenteric artery embolism

    Institute of Scientific and Technical Information of China (English)

    吕和平; 倪海真; 黄景勇; 陈祥建; 虞冠锋

    2016-01-01

    .8例患者肠系膜上动脉主干栓塞呈低密度影,伴远端分支动脉显影,其中肠缺血3例,部分肠坏死4例,长段肠坏死1例.2例患者肠系膜上动脉非主干栓塞呈低密度影,伴远端分支动脉不显影,均为部分肠坏死.3例患者肠系膜上动脉非主干栓塞呈低密度影,伴远端分支动脉显影,其中肠缺血2例,部分肠坏死1例.②间接征象:5例患者肠壁增厚,其中部分肠坏死3例,长段肠坏死2例.17例患者肠道扩张伴积气、积液,局部肠管内可见气液平,其中肠缺血2例,部分肠坏死5例,长段肠坏死10例.2例患者肠壁积气,呈肠壁气泡影,均为长段肠坏死.(4)治疗及预后:6例肠缺血患者,其中1例行肠系膜上动脉取栓术,其余5例行低分子肝素抗凝、前列地尔扩血管等治疗.8例部分肠坏死患者,行坏死肠管切除术.12例长段肠坏死患者中,5例术后短肠综合征行坏死肠管切除术,术后联合静脉营养支持治疗.上述患者均经对症支持和手术治疗好转出院.12例长段肠坏死患者中,7例全小肠坏死及部分结肠坏死仅行剖腹探查,短期内死亡.结论 肌酸激酶明显升高及CT血管造影检查示肠系膜上动脉主干栓塞伴远端分支不显影,预示肠系膜上动脉栓塞患者短期不良预后.%Objective To investigate the value of creatine kinase and computed tomography(CT)angiography to evaluate short-term prognosis of patients with superior mesenteric artery embolism(SMAE).Methods The retrospective cross-sectional study was adopted.The clinical data of 26 patients with SMAE who were admitted to the first Affiliated Hospital of Wenzhou Medical University between January 2008 and October 2015 were collected.The patients received serologic examination and CT angiography firstly,and then medicinal conservative method and surgical method were respectively conducted according to the results of above examinations.Observation indices:(1)clinical features,(2)serum indicators

  4. Stabilization of the cyclin-dependent kinase 5 activator, p35, by paclitaxel decreases beta-amyloid toxicity in cortical neurons.

    Science.gov (United States)

    Li, Guibin; Faibushevich, Alexander; Turunen, Brandon J; Yoon, Sung Ok; Georg, Gunda; Michaelis, Mary L; Dobrowsky, Rick T

    2003-01-01

    One hallmark of Alzheimer's disease (AD) is the formation of neurofibrillary tangles, aggregated paired helical filaments composed of hyperphosphorylated tau. Amyloid-beta (Abeta) induces tau hyperphosphorylation, decreases microtubule (MT) stability and induces neuronal death. MT stabilizing agents have been proposed as potential therapeutics that may minimize Abeta toxicity and here we report that paclitaxel (taxol) prevents cell death induced by Abeta peptides, inhibits Abeta-induced activation of cyclin-dependent kinase 5 (cdk5) and decreases tau hyperphosphorylation. Taxol did not inhibit cdk5 directly but significantly blocked Abeta-induced calpain activation and decreased formation of the cdk5 activator, p25, from p35. Taxol specifically inhibited the Abeta-induced activation of the cytosolic cdk5-p25 complex, but not the membrane-associated cdk5-p35 complex. MT-stabilization was necessary for neuroprotection and inhibition of cdk5 but was not sufficient to prevent cell death induced by overexpression of p25. As taxol is not permeable to the blood-brain barrier, we assessed the potential of taxanes to attenuate Abeta toxicity in adult animals using a succinylated taxol analog (TX67) permeable to the blood-brain barrier. TX67, but not taxol, attenuated the magnitude of both basal and Abeta-induced cdk5 activation in acutely dissociated cortical cultures prepared from drug treated adult mice. These results suggest that MT-stabilizing agents may provide a therapeutic approach to decrease Abeta toxicity and neurofibrillary pathology in AD and other tauopathies.

  5. Creatine synthesis and exchanges between brain cells: What can be learned from human creatine deficiencies and various experimental models?

    Science.gov (United States)

    Hanna-El-Daher, Layane; Braissant, Olivier

    2016-08-01

    While it has long been thought that most of cerebral creatine is of peripheral origin, the last 20 years has provided evidence that the creatine synthetic pathway (AGAT and GAMT enzymes) is expressed in the brain together with the creatine transporter (SLC6A8). It has also been shown that SLC6A8 is expressed by microcapillary endothelial cells at the blood-brain barrier, but is absent from surrounding astrocytes, raising the concept that the blood-brain barrier has a limited permeability for peripheral creatine. The first creatine deficiency syndrome in humans was also discovered 20 years ago (GAMT deficiency), followed later by AGAT and SLC6A8 deficiencies, all three diseases being characterized by creatine deficiency in the CNS and essentially affecting the brain. By reviewing the numerous and latest experimental studies addressing creatine transport and synthesis in the CNS, as well as the clinical and biochemical characteristics of creatine-deficient patients, our aim was to delineate a clearer view of the roles of the blood-brain and blood-cerebrospinal fluid barriers in the transport of creatine and guanidinoacetate between periphery and CNS, and on the intracerebral synthesis and transport of creatine. This review also addresses the question of guanidinoacetate toxicity for brain cells, as probably found under GAMT deficiency.

  6. Elevated plasma creatinine due to creatine ethyl ester use.

    Science.gov (United States)

    Velema, M S; de Ronde, W

    2011-02-01

    Creatine is a nutritional supplement widely used in sport, physical fitness training and bodybuilding. It is claimed to enhance performance. We describe a case in which serum creatinine is elevated due to the use of creatine ethyl esther. One week after withdrawal, the plasma creatinine had normalised. There are two types of creatine products available: creatine ethyl esther (CEE) and creatine monohydrate (CM). Plasma creatinine is not elevated in all creatine-using subjects. CEE , but not CM, is converted into creatinine in the gastrointestinal tract. As a result the use of CEE may be associated with elevated plasma creatinine levels. Since plasma creatinine is a widely used marker for renal function, the use of CEE may lead to a false assumption of renal failure.

  7. Changes of BB Isoenzyme of Creatine Kinase, CaATPase and Calpain in Experimental Autoimmune Encephalomyelitis Mouse Brain and Spinal Cord%实验性自身免疫性脑脊髓炎小鼠脑组织和脊髓中脑型肌酸激酶、钙泵和钙中性蛋白酶的变化

    Institute of Scientific and Technical Information of China (English)

    王沛; 郑荣远; 林福虹; 王赵伟; 厉芳; 张正学

    2011-01-01

    Aim: To investigate the changes ofBB isoenzyme of creatine kinase(CK-BB), CaATPase and calpain in experimental autoimmune encephalomyelitis(EAE) mouse brain and spinal cord. Methods: C57BL/6 mice were induced into the models of EAE with multiple sclerosis by myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) peptides. Behavioral changes of the EAE mice were observed and recorded. With HE staining, LFB myelin staining, the changes of the central nervous tissues, CK-BB, CaATPase and calpain activity were assayed in the peak incidence by using microplate reader and spectrophotometer (19 days after immunization). Results: Compared with the control group, the results of the EAE group were as follows :① Mean daily clinical scores and cumulative scores were mcreased(P<0.01).② HE staining: Central inflammatory cell infiltration became obvious(P<0.05).③ LFB Clinical Analysis of 15 Cases with Spontaneous Intracranial Hypotension HeadacheKEY WORDS spontaneous intracranial hypotension; headache; secondary headacheABSTRACT Aim: To explore the clinical features of spontaneous intracranial hypotension(SIH) headache.Methods: Clinical data of 15 cases of SIH headache were retrospectively analyzed. Results: 12 0f 15 caseswere acute onset, 9 were female. The ages of onset were from 28 t0 56 years. 93.33% cases had posturalheadache, with the common concomitant symptoms of nausea and vomit. The average cerebrospinal fluidpressure was (41.2 + 30.85)mmH20, which was higher in male than in female (P<0.05). Radionuclidecisternography and imaging were normal. All cases were cured after conservative treatment. Conclusion:Typical postural headache and cerebrospinal fluid pressure less than 60 mmH.O were the main features in SIHheadache, which were with favorable prognosis.%目的:观察实验性自身免疫性脑脊髓炎(EAE)小鼠模型脑组织和脊髓中脑型肌酸激酶(CK-BB)、钙泵(CaATPase) 和钙中性蛋白酶(calpain)的变化.方法:C57BL/6

  8. Creatine Supplementation and Swim Performance: A Brief Review

    OpenAIRE

    Hopwood, Melissa J.; Kenneth Graham; Kieron B Rooney

    2006-01-01

    Nutritional supplements are popular among athletes participating in a wide variety of sports. Creatine is one of the most commonly used dietary supplements, as it has been shown to be beneficial in improving performance during repeated bouts of high-intensity anaerobic activity. This review examines the specific effects of creatine supplementation on swimming performance, and considers the effects of creatine supplementation on various measures of power development in this population. Researc...

  9. 21 CFR 862.1210 - Creatine test system.

    Science.gov (United States)

    2010-04-01

    ..., serum, and urine. Measurements of creatine are used in the diagnosis and treatment of muscle diseases and endocrine disorders including hyperthyroidism. (b) Classification. Class I (general controls)....

  10. Unchanged mitochondrial organization and compartmentation of high-energy phosphates in creatine-deficient GAMT-/- mouse hearts.

    Science.gov (United States)

    Branovets, Jelena; Sepp, Mervi; Kotlyarova, Svetlana; Jepihhina, Natalja; Sokolova, Niina; Aksentijevic, Dunja; Lygate, Craig A; Neubauer, Stefan; Vendelin, Marko; Birkedal, Rikke

    2013-08-15

    Disruption of the creatine kinase (CK) system in hearts of CK-deficient mice leads to changes in the ultrastructure and regulation of mitochondrial respiration. We expected to see similar changes in creatine-deficient mice, which lack the enzyme guanidinoacetate methyltransferase (GAMT) to produce creatine. The aim of this study was to characterize the changes in cardiomyocyte mitochondrial organization, regulation of respiration, and intracellular compartmentation associated with GAMT deficiency. Three-dimensional mitochondrial organization was assessed by confocal microscopy. On populations of permeabilized cardiomyocytes, we recorded ADP and ATP kinetics of respiration, competition between mitochondria and pyruvate kinase for ADP produced by ATPases, ADP kinetics of endogenous pyruvate kinase, and ATP kinetics of ATPases. These data were analyzed by mathematical models to estimate intracellular compartmentation. Quantitative analysis of morphological and kinetic data as well as derived model fits showed no difference between GAMT-deficient and wild-type mice. We conclude that inactivation of the CK system by GAMT deficiency does not alter mitochondrial organization and intracellular compartmentation in relaxed cardiomyocytes. Thus, our results suggest that the healthy heart is able to preserve cardiac function at a basal level in the absence of CK-facilitated energy transfer without compromising intracellular organization and the regulation of mitochondrial energy homeostasis. This raises questions on the importance of the CK system as a spatial energy buffer in unstressed cardiomyocytes.

  11. Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo.

    Science.gov (United States)

    Sun, G; Tarasov, A I; McGinty, J; McDonald, A; da Silva Xavier, G; Gorman, T; Marley, A; French, P M; Parker, H; Gribble, F; Reimann, F; Prendiville, O; Carzaniga, R; Viollet, B; Leclerc, I; Rutter, G A

    2010-05-01

    AMP-activated protein kinase (AMPK) is an evolutionarily conserved enzyme and a target of glucose-lowering agents, including metformin. However, the precise role or roles of the enzyme in controlling insulin secretion remain uncertain. The catalytic alpha1 and alpha2 subunits of AMPK were ablated selectively in mouse pancreatic beta cells and hypothalamic neurons by breeding Ampkalpha1 [also known as Prkaa1]-knockout mice, bearing floxed Ampkalpha2 [also known as Prkaa2] alleles (Ampkalpha1 ( -/- ),alpha2( fl/fl ),), with mice expressing Cre recombinase under the rat insulin promoter (RIP2). RIP2 was used to express constitutively activated AMPK selectively in beta cells in transgenic mice. Food intake, body weight and urinary catecholamines were measured using metabolic cages. Glucose and insulin tolerance were determined after intraperitoneal injection. Beta cell mass and morphology were analysed by optical projection tomography and confocal immunofluorescence microscopy, respectively. Granule docking, insulin secretion, membrane potential and intracellular free Ca(2+) were measured with standard techniques. Trigenic Ampkalpha1 ( -/- ),alpha2( fl/fl ) expressing Cre recombinase and lacking both AMPKalpha subunits in the beta cell, displayed normal body weight and increased insulin sensitivity, but were profoundly insulin-deficient. Secreted catecholamine levels were unchanged. Total beta cell mass was unaltered, while mean islet and beta cell volume were reduced. AMPK-deficient beta cells displayed normal glucose-induced changes in membrane potential and intracellular free Ca(2+), while granule docking and insulin secretion were enhanced. Conversely, betaAMPK transgenic mice were glucose-intolerant and displayed defective insulin secretion. Inhibition of AMPK activity within the beta cell is necessary, but not sufficient for stimulation of insulin secretion by glucose to occur. AMPK activation in extrapancreatic RIP2.Cre-expressing cells might also influence

  12. The effect of longer-term creatine supplementation on elite swimming performance after an acute creatine loading.

    Science.gov (United States)

    Theodorou, A S; Cooke, C B; King, R F; Hood, C; Denison, T; Wainwright, B G; Havenetidis, K

    1999-11-01

    We investigated the effect of an acute creatine loading (25 g per day for 4 days) and longer-term creatine supplementation (5 g of creatine or 5 g of placebo per day for 2 months) on the performance of 22 elite swimmers during maximal interval sessions. After the acute creatine loading, the mean of the average interval swim times for all swimmers (n = 22) improved (44.3+/-16.5 s before vs. 43.7+/-16.3 s after supplementation; Pswimmers did not respond positively to supplementation. After 2 months of longer-term creatine supplementation or placebo, neither group showed a significant change in swimming performance (38.7+/-13.5 s before vs. 38.7+/-14.1 s after for the creatine group; 48.7+/-18.0 s before vs. 48.7+/-18.1 s after for the placebo group). We conclude that, in elite swimmers, 4 days of acute creatine loading improves swimming performance significantly when assessed by maximal interval sessions. However, longer-term supplementation for 2 months (5 g of creatine per day) did not benefit significantly the creatine group compared with the placebo group.

  13. Single Prolonged Stress Decreases Glutamate, Glutamine, and Creatine Concentrations In The Rat Medial Prefrontal Cortex

    Science.gov (United States)

    Knox, Dayan; Perrine, Shane A.; George, Sophie A.; Galloway, Matthew P.; Liberzon, Israel

    2010-01-01

    Application of Single Prolonged Stress (SPS) in rats induces changes in neuroendocrine function and arousal that are characteristic of Post Traumatic Stress Disorder (PTSD). PTSD, in humans, is associated with decreased neural activity in the prefrontal cortex, increased neural activity in the amygdala complex, and reduced neuronal integrity in the hippocampus. However, the extent to which SPS models these aspects of PTSD has not been established. In order to address this, we used high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H MRS) ex vivo to assay levels of neurochemicals critical for energy metabolism (creatine and lactate), excitatory (glutamate and glutamine) and inhibitory (gamma amino butyric acid (GABA)) neurotransmission, and neuronal integrity (N-acetyl aspartate (NAA)) in the medial prefrontal cortex (mPFC), amygdala complex, and hippocampus of SPS and control rats. Glutamate, glutamine, and creatine levels were decreased in the mPFC of SPS rats when compared to controls, which suggests decreased excitatory tone in this region. SPS did not alter the neurochemical profiles of either the hippocampus or amygdala. These data suggest that SPS selectively attenuates excitatory tone, without a disruption of neuronal integrity, in the mPFC. PMID:20546834

  14. The forced swimming-induced behavioural immobility response involves histone H3 phospho-acetylation and c-Fos induction in dentate gyrus granule neurons via activation of the N-methyl-D-aspartate/extracellular signal-regulated kinase/mitogen- and stress-activated kinase signalling pathway.

    Science.gov (United States)

    Chandramohan, Yalini; Droste, Susanne K; Arthur, J Simon C; Reul, Johannes M H M

    2008-05-01

    The hippocampus is involved in learning and memory. Previously, we have shown that the acquisition of the behavioural immobility response after a forced swim experience is associated with chromatin modifications and transcriptional induction in dentate gyrus granule neurons. Given that both N-methyl-D-aspartate (NMDA) receptors and the extracellular signal-regulated kinases (ERK) 1/2 signalling pathway are involved in neuroplasticity processes underlying learning and memory, we investigated in rats and mice whether these signalling pathways regulate chromatin modifications and transcriptional events participating in the acquisition of the immobility response. We found that: (i) forced swimming evoked a transient increase in the number of phospho-acetylated histone H3-positive [P(Ser10)-Ac(Lys14)-H3(+)] neurons specifically in the middle and superficial aspects of the dentate gyrus granule cell layer; (ii) antagonism of NMDA receptors and inhibition of ERK1/2 signalling blocked forced swimming-induced histone H3 phospho-acetylation and the acquisition of the behavioural immobility response; (iii) double knockout (DKO) of the histone H3 kinase mitogen- and stress-activated kinases (MSK) 1/2 in mice completely abolished the forced swimming-induced increases in histone H3 phospho-acetylation and c-Fos induction in dentate granule neurons and the behavioural immobility response; (iv) blocking mineralocorticoid receptors, known not to be involved in behavioural immobility in the forced swim test, did not affect forced swimming-evoked histone H3 phospho-acetylation in dentate neurons; and (v) the pharmacological manipulations and gene deletions did not affect behaviour in the initial forced swim test. We conclude that the forced swimming-induced behavioural immobility response requires histone H3 phospho-acetylation and c-Fos induction in distinct dentate granule neurons through recruitment of the NMDA/ERK/MSK 1/2 pathway.

  15. The effect of the creatine analogue beta-guanidinopropionic acid on energy metabolism: a systematic review.

    Directory of Open Access Journals (Sweden)

    Inge Oudman

    Full Text Available BACKGROUND: Creatine kinase plays a key role in cellular energy transport. The enzyme transfers high-energy phosphoryl groups from mitochondria to subcellular sites of ATP hydrolysis, where it buffers ADP concentration by catalyzing the reversible transfer of the high-energy phosphate moiety (P between creatine and ADP. Cellular creatine uptake is competitively inhibited by beta-guanidinopropionic acid. This substance is marked as safe for human use, but the effects are unclear. Therefore, we systematically reviewed the effect of beta-guanidinopropionic acid on energy metabolism and function of tissues with high energy demands. METHODS: We performed a systematic review and searched the electronic databases Pubmed, EMBASE, the Cochrane Library, and LILACS from their inception through March 2011. Furthermore, we searched the internet and explored references from textbooks and reviews. RESULTS: After applying the inclusion criteria, we retrieved 131 publications, mainly considering the effect of chronic oral administration of beta-guanidinopropionic acid (0.5 to 3.5% on skeletal muscle, the cardiovascular system, and brain tissue in animals. Beta-guanidinopropionic acid decreased intracellular creatine and phosphocreatine in all tissues studied. In skeletal muscle, this effect induced a shift from glycolytic to oxidative metabolism, increased cellular glucose uptake and increased fatigue tolerance. In heart tissue this shift to mitochondrial metabolism was less pronounced. Myocardial contractility was modestly reduced, including a decreased ventricular developed pressure, albeit with unchanged cardiac output. In brain tissue adaptations in energy metabolism resulted in enhanced ATP stability and survival during hypoxia. CONCLUSION: Chronic beta-guanidinopropionic acid increases fatigue tolerance of skeletal muscle and survival during ischaemia in animal studies, with modestly reduced myocardial contractility. Because it is marked as safe for human

  16. The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC Trial): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Karamat, Fares A; Horjus, Deborah L; Haan, Yentl C; van der Woude, Lisa; Oudman, Inge; van Montfrans, Gert A; Clark, Joseph F; Brewster, Lizzy M

    2015-02-22

    Despite adequate treatment, up to 30% of treated antihypertensive patients with primary, uncomplicated hypertension remain uncontrolled. We proposed that high intracellular activity of the ATP regenerating enzyme creatine kinase (CK) increases pressor responses and hypertension risk. In line with this, we found that plasma CK activity after rest, a surrogate measure of tissue activity, is the main predictor of blood pressure levels and failure of antihypertensive therapy in the general population. In addition, the creatine analog and competitive oral creatine kinase inhibitor beta-guanidinopropionic acid effectively and safely reduced blood pressure in the spontaneously hypertensive rat. However, to our knowledge there are no human data on the safety of oral supplementation with this substance. Therefore, we will assess the tolerability of beta-guanidinopropionic acid in men, compared to creatine and placebo. This is a randomized, active and placebo controlled, triple blind, double dummy, single center clinical intervention trial in 24 healthy male volunteers, 18 to 50 years old, recruited in the Netherlands. The intervention consists of one week of daily oral administration of beta-guanidinopropionic acid 100 mg, creatine 5 gram, or placebo. The primary outcome is the tolerability of beta-guanidinopropionic acid as a descriptive measure, in an intent-to-treat analysis. Other outcomes include the placebo-adjusted differences with baseline in biochemical and hemodynamic parameters, including plasma markers of muscle tissue damage, urine sodium excretion, resting sitting systolic and diastolic brachial blood pressure, supine systolic and diastolic central blood pressure, pulse wave velocity and augmentation index, heart rate, cardiac contractility, cardiac output, and total peripheral resistance. There is an unfulfilled need for new conservative options to treat resistant hypertension. This study will provide first-in-men data on creatine kinase inhibition as a

  17. Creatine Use and Exercise Heat Tolerance in Dehydrated Men

    OpenAIRE

    Watson, Greig; Casa, Douglas J.; Fiala, Kelly A; Hile, Amy; Roti, Melissa W; Healey, Julie C; Armstrong, Lawrence E; Maresh, Carl M.

    2006-01-01

    Context: Creatine monohydrate (CrM) use is highly prevalent in team sports (eg, football, lacrosse, ice hockey) and by athletes at the high school, college, professional, and recreational levels. Concerns have been raised about whether creatine use is associated with increased cramping, muscle injury, heat intolerance, and risk of dehydration.

  18. Creatine supplementation and swim performance: a brief review.

    Science.gov (United States)

    Hopwood, Melissa J; Graham, Kenneth; Rooney, Kieron B

    2006-03-01

    Nutritional supplements are popular among athletes participating in a wide variety of sports. Creatine is one of the most commonly used dietary supplements, as it has been shown to be beneficial in improving performance during repeated bouts of high-intensity anaerobic activity. This review examines the specific effects of creatine supplementation on swimming performance, and considers the effects of creatine supplementation on various measures of power development in this population. Research performed on the effect of creatine supplementation on swimming performance indicates that whilst creatine supplementation is ineffective in improving performance during a single sprint swim, dietary creatine supplementation may benefit repeated interval swim set performance. Considering the relationship between sprint swimming performance and measurements of power, the effect of creatine supplementation on power development in swimmers has also been examined. When measured on a swim bench ergometer, power development does show some improvement following a creatine supplementation regime. How this improvement in power output transfers to performance in the pool is uncertain. Although some evidence exists to suggest a gender effect on the performance improvements seen in swimmers following creatine supplementation, the majority of research indicates that male and female swimmers respond equally to supplementation. A major limitation to previous research is the lack of consideration given to the possible stroke dependant effect of creatine supplementation on swimming performance. The majority of the research conducted to date has involved examination of the freestyle swimming stroke only. The potential for performance improvements in the breaststroke and butterfly swimming strokes is discussed, with regards to the biomechanical differences and differences in efficiency between these strokes and freestyle. Key PointsCreatine supplementation does not improve single sprint

  19. Creatine, energetic function, metabolism and supplementation effects on sports

    Directory of Open Access Journals (Sweden)

    Emerson Gimenes Bernardo da Silva

    2008-06-01

    Full Text Available The purpose of this work is to review the literature regarding creatine ingestion by athletes and physical activity enthusiasts, discussing its necessity and, if possible, predicting some consequences. In order to achieve this purpose it was necessary to study the relationship between the muscles energetic system and their regulation. It was also proved necessary to investigate the creatine cycle, its endogenous origin, its metabolizing and conversion into creatine-phosphate. A bibliography was used to collect information about the subject. The research lead to the following conclusions: diet supplementation with creatine leads to increased phosphocreatine levels in human muscles. However, new in vivo experiments are most desirable, because it is already known that creatine interferes with the regulation of some metabolic pathways.

  20. Creatine supplementation reduces doxorubicin-induced cardiomyocellular injury.

    Science.gov (United States)

    Santacruz, Lucia; Darrabie, Marcus D; Mantilla, Jose Gabriel; Mishra, Rajashree; Feger, Bryan J; Jacobs, Danny O

    2015-04-01

    Heart failure is a common complication of doxorubicin (DOX) therapy. Previous studies have shown that DOX adversely impacts cardiac energy metabolism, and the ensuing energy deficiencies antedate clinical manifestations of cardiac toxicity. Brief exposure of cultured cardiomyocytes to DOX significantly decreases creatine transport, which is the cell's sole source of creatine. We present the results of a study performed to determine if physiological creatine supplementation (5 mmol/L) could protect cardiomyocytes in culture from cellular injury resulting from exposure to therapeutic levels of DOX. Creatine supplementation significantly decreased cytotoxicity, apoptosis, and reactive oxygen species production caused by DOX. The protective effect was specific to creatine and depended on its transport into the cell.

  1. The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and ~P transferring kinases

    Science.gov (United States)

    Rueda, Elda M.; Johnson, Jerry E.; Giddabasappa, Anand; Swaroop, Anand; Brooks, Matthew J.; Sigel, Irena; Chaney, Shawnta Y.

    2016-01-01

    inner segments. The combined results indicate that glycolysis is regulated by the compartmental expression of hexokinase 2, pyruvate kinase M1, and pyruvate kinase M2 in photoreceptors, whereas the inner retinal neurons exhibit a lower capacity for glycolysis and aerobic glycolysis. Expression of nucleoside diphosphate kinase, mitochondria-associated adenylate kinase, and several mitochondria-associated creatine kinase isozymes was highest in the outer retina, whereas expression of cytosolic adenylate kinase and brain creatine kinase was higher in the cones, horizontal cells, and amacrine cells indicating the diversity of ATP-buffering strategies among retinal neurons. Based on the antibody intensities and the COX and LDH activity, Müller glial cells (MGCs) had the lowest capacity for glycolysis, aerobic glycolysis, and OXPHOS. However, they showed high expression of glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate thiokinase, GABA transaminase, and ~P transferring kinases. This suggests that MGCs utilize TCA cycle anaplerosis and cataplerosis to generate GTP and ~P transferring kinases to produce ATP that supports MGC energy requirements. Conclusions Our comprehensive and integrated results reveal that the adult mouse retina expresses numerous isoforms of ATP synthesizing, regulating, and buffering genes; expresses differential cellular and compartmental levels of glycolytic, OXPHOS, TCA cycle, and ~P transferring kinase proteins; and exhibits differential layer-by-layer LDH and COX activity. New insights into cell-specific and compartmental ATP and GTP production, as well as utilization and buffering strategies and their relationship with known retinal and cellular functions, are discussed. Developing therapeutic strategies for neuroprotection and treating retinal deficits and degeneration in a cell-specific manner will require such knowledge. This work provides a platform for future research directed at identifying the molecular targets and

  2. CREATINE SUPPLEMENTATION AND SWIM PERFORMANCE: A BRIEF REVIEW

    Directory of Open Access Journals (Sweden)

    Melissa J. Hopwood

    2006-03-01

    Full Text Available Nutritional supplements are popular among athletes participating in a wide variety of sports. Creatine is one of the most commonly used dietary supplements, as it has been shown to be beneficial in improving performance during repeated bouts of high-intensity anaerobic activity. This review examines the specific effects of creatine supplementation on swimming performance, and considers the effects of creatine supplementation on various measures of power development in this population. Research performed on the effect of creatine supplementation on swimming performance indicates that whilst creatine supplementation is ineffective in improving performance during a single sprint swim, dietary creatine supplementation may benefit repeated interval swim set performance. Considering the relationship between sprint swimming performance and measurements of power, the effect of creatine supplementation on power development in swimmers has also been examined. When measured on a swim bench ergometer, power development does show some improvement following a creatine supplementation regime. How this improvement in power output transfers to performance in the pool is uncertain. Although some evidence exists to suggest a gender effect on the performance improvements seen in swimmers following creatine supplementation, the majority of research indicates that male and female swimmers respond equally to supplementation. A major limitation to previous research is the lack of consideration given to the possible stroke dependant effect of creatine supplementation on swimming performance. The majority of the research conducted to date has involved examination of the freestyle swimming stroke only. The potential for performance improvements in the breaststroke and butterfly swimming strokes is discussed, with regards to the biomechanical differences and differences in efficiency between these strokes and freestyle

  3. Total-body creatine pool size and skeletal muscle mass determination by creatine-(methyl-d3) dilution in rats

    National Research Council Canada - National Science Library

    Stephen A. Stimpson; Scott M. Turner; Lisa G. Clifton; James C. Poole; Hussein A. Mohammed; Todd W. Shearer; Greg M. Waitt; Laura L. Hagerty; Katja S. Remlinger; Marc K. Hellerstein; William J. Evans

    2012-01-01

    .... We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d3) (D3-creatinine) in urine after a defined oral tracer dose of D3-creatine can be used to determine creatine pool size and skeletal muscle mass...

  4. Creatine supplementation does not decrease oxidative stress and inflammation in skeletal muscle after eccentric exercise.

    Science.gov (United States)

    Silva, Luciano A; Tromm, Camila B; Da Rosa, Guilherme; Bom, Karoliny; Luciano, Thais F; Tuon, Talita; De Souza, Cláudio T; Pinho, Ricardo A

    2013-01-01

    Thirty-six male rats were used; divided into 6 groups (n = 6): saline; creatine (Cr); eccentric exercise (EE) plus saline 24 h (saline + 24 h); eccentric exercise plus Cr 24 h (Cr + 24 h); eccentric exercise plus saline 48 h (saline + 48 h); and eccentric exercise plus Cr 48 h (Cr + 48 h). Cr supplementation was administered as a solution of 300 mg · kg body weight(-1) · day(-1) in 1 mL water, for two weeks, before the eccentric exercise. The animals were submitted to one downhill run session at 1.0 km · h(-1) until exhaustion. Twenty-four and forty-eight hours after the exercise, the animals were killed, and the quadriceps were removed. Creatine kinase levels, superoxide production, thiobarbituric acid reactive substances (TBARS) level, carbonyl content, total thiol content, superoxide dismutase, catalase, glutathione peroxidase, interleukin-1b (IL-1β), nuclear factor kappa B (NF-kb), and tumour necrosis factor (TNF) were analysed. Cr supplementation neither decreases Cr kinase, superoxide production, lipoperoxidation, carbonylation, total thiol, IL-1β, NF-kb, or TNF nor alters the enzyme activity of superoxide dismutase, catalase, and glutathione peroxides in relation to the saline group, respectively (P eccentric exercise. The present study suggests that Cr supplementation does not decrease oxidative stress and inflammation after eccentric contraction.

  5. The effects of creatine pyruvate and creatine citrate on performance during high intensity exercise

    Directory of Open Access Journals (Sweden)

    Purpura Martin

    2008-02-01

    Full Text Available Abstract Background A double-blind, placebo-controlled, randomized study was performed to evaluate the effect of oral creatine pyruvate (Cr-Pyr and creatine citrate (Cr-Cit supplementation on exercise performance in healthy young athletes. Methods Performance during intermittent handgrip exercise of maximal intensity was evaluated before (pretest and after (posttest 28 days of Cr-Pyr (5 g/d, n = 16, Cr-Cit (5 g/d, n = 16 or placebo (pla, 5 g/d, n = 17 intake. Subjects performed ten 15-sec exercise intervals, each followed by 45 sec rest periods. Results Cr-Pyr (p Conclusion It is concluded that four weeks of Cr-Pyr and Cr-Cit intake significantly improves performance during intermittent handgrip exercise of maximal intensity and that Cr-Pyr might benefit endurance, due to enhanced activity of the aerobic metabolism.

  6. Functional expression of phosphagen kinase systems confers resistance to transient stresses in Saccharomyces cerevisiae by buffering the ATP pool.

    Science.gov (United States)

    Canonaco, Fabrizio; Schlattner, Uwe; Pruett, Pamela S; Wallimann, Theo; Sauer, Uwe

    2002-08-30

    Phosphagen kinase systems provide different advantages to tissues with high and fluctuating energy demands, in particular an efficient energy buffering system. In this study we show for the first time functional expression of two phosphagen kinase systems in Saccharomyces cerevisiae, which does not normally contain such systems. First, to establish the creatine kinase system, in addition to overexpressing creatine kinase isoenzymes, we had to install the biosynthesis pathway of creatine by co-overexpression of L-arginine:glycine amidinotransferase and guanidinoacetate methyltransferase. Although we could achieve considerable creatine kinase activity, together with more than 3 mM intracellular creatine, this was not sufficient to confer an obvious advantage to the yeast under the specific stress conditions examined here. Second, using arginine kinase, we successfully installed an intracellular phosphagen pool of about 5 mM phosphoarginine. Such arginine kinase-expressing yeast showed improved resistance under two stress challenges that drain cellular energy, which were transient pH reduction and starvation. Although transient starvation led to 50% reduced intracellular ATP concentrations in wild-type yeast, arginine kinase overexpression stabilized the ATP pool at the pre-stress level. Thus, our results demonstrate that temporal energy buffering is an intrinsic property of phosphagen kinases that can be transferred to phylogenetically very distant organisms.

  7. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    Science.gov (United States)

    Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

    2015-09-01

    There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or cr