caenorhabditis elegans homeostasis: Topics by WorldWideScience.org

P granules are non-membrane-bound organelles found in the germ-line cytoplasm throughout Caenorhabditis elegans development. Like their “germ granule” counterparts in...Full Text Available

2009-12-01

Global 'worming'

Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB

A report on the 16th International Caenorhabditis elegans Meeting, Los Angeles, USA, 27 June-1 July 2007.

2007-01-01

A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans

Activating AMPK or inactivating calcineurin slows ageing in Caenorhabditis elegans^1,2...Full Text Available

2011-02-17

Zebrafish TRPA1 Channels are Required for Chemosensation but not for Thermosensation or Mechanosensory Hair Cell Function

The nuo-6 and isp-1 genes of C. elegans encode, respectively, subunits of complex I and III of the mitochondrial respiratory chain. Partial loss-of-function...Full Text Available

2010-12-01

Variable Pathogenicity Determines Individual Lifespan in Caenorhabditis elegans

Transient receptor potential (TRP) ion channels have been implicated in detecting chemical, thermal and mechanical stimuli in organisms ranging from mammals to Caenorhabditis elegans....Full Text Available

2008-10-01

The Dystrophin Complex Controls BK Channel Localization and Muscle Activity in Caenorhabditis elegans

A common property of aging in all animals is that chronologically and genetically identical individuals age at different rates. To unveil mechanisms that influence aging variability, we identified markers...Full Text Available

2011-04-01

The Caenorhabditis elegans Elongator Complex Regulates Neuronal ?-tubulin Acetylation

Genetic defects in the dystrophin-associated protein complex (DAPC) are responsible for a variety of pathological conditions including muscular dystrophy, cardiomyopathy, and vasospasm. Conserved DAPC...Full Text Available

2009-12-01

Stressed-Induced TMEM135 Protein Is Part of a Conserved Genetic Network Involved in Fat Storage and Longevity Regulation in Caenorhabditis elegans

Although acetylated α-tubulin is known to be a marker of stable microtubules in neurons, precise factors that regulate α-tubulin acetylation are, to date, largely unknown. Therefore,...Full Text Available

2010-01-01

Regulation of DAF-16-mediated Innate Immunity in Caenorhabditis elegans*

Disorders of mitochondrial fat metabolism lead to sudden death in infants and children. Although survival is possible, the underlying molecular mechanisms which enable this outcome have not yet been...Full Text Available

Purpose and regulation of stem cells: a systems-biology view from the Caenorhabditis elegans germ line

Activation of the innate immune system results in a rapid microbicidal response against microorganisms, which needs to be fine-tuned because uncontrolled immune responses can lead to infection and cancer,...Full Text Available

2009-12-18

PDP-1 Links the TGF-? and IIS Pathways to Regulate Longevity, Development, and Metabolism

Stem cells are expected to play a key role in the development and maintenance of organisms, and hold great therapeutic promises. However, a number of questions must be answered to achieve an...Full Text Available

2009-01-01

Membrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of Klebsiella pneumoniae in a Caenorhabditis elegans Model?

The insulin/IGF-1 signaling (IIS) pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation of DAF-2 (insulin/IGF-1...Full Text Available

2011-04-01

A Decline in p38 MAPK Signaling Underlies Immunosenescence in Caenorhabditis elegans

Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella...Full Text Available

2010-10-01

Disruption of the ATP-binding Cassette B7 (ABTM-1/ABCB7) Induces Oxidative Stress and Premature Cell Death in Caenorhabditis elegans*

The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging...Full Text Available

2011-05-01

A Role for Set1/MLL-Related Components in Epigenetic Regulation of the Caenorhabditis elegans Germ Line

X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare inherited disorder characterized by mild anemia and ataxia. XLSA/A is caused by mutations in the ABCB7 gene, which encodes...Full Text Available

2011-06-17

C. elegans as a model for stem cell biology

The methylation of lysine 4 of Histone H3 (H3K4me) is an important component of epigenetic regulation. H3K4 methylation is a consequence of transcriptional activity, but also has been shown to contribute...Full Text Available

2011-03-01

Calcineurin may regulate multiple endocytic processes in C. elegans

We review the application of C. elegans as a model system to understand key aspects of stem cell biology. The only bona fide stem cells in C. elegans...Full Text Available

2010-05-01

KoreaScience (Korea)

Full Text Available

2011-02-01

Perinuclear P granules are the principal sites of mRNA export in adult C. elegans germ cells

Synthetic Biology and Human Health: Potential Applications for Spaceflight

Germline-specific granules of unknown function are found in a wide variety of organisms, including C. elegans, where they are called P granules. P granules are cytoplasmic bodies...Full Text Available

2010-04-15

1 2 3 4 5

Phosphorus and calcium homeostasis in chronic subtotally nephrectomized parathyroidectomized rats.

Human space travelers experience a unique environment that affects homeostasis and physiologic

2011-01-01

KoreaScience (Korea)

Full Text Available

Impairing Effects of Acute Glucose Overload on Calcium Homeostasis in Vascular Endothelial Cells

KoreaScience (Korea)

Full Text Available

1998-12-01

Effect of nitric oxide on endoplasmic reticulum calcium homeostasis, protein synthesis and energy metabolism

DEFF Research Database (Denmark)

ATPase, endoplasmic reticulum, calcium, ischaemia

2000-01-01

Simultaneous recognition and segmentation of cells: application in C.elegans

Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis

Motivation: Automatic recognition of cell identities is critical for quantitative measurement, targeting and manipulation of cells of model animals at single-cell resolution. It has been...Full Text Available

2011-10-15

Hypothalamic control of energy and glucose metabolism

Eosinophils are associated with helminth immunity and allergy, often in conjunction with alternatively activated macrophages (AAMs). Adipose tissue AAMs are necessary to maintain glucose homeostasis...Full Text Available

2011-04-08

British Library Electronic Table of Contents (United Kingdom)

The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

2011-01-01

Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae

The Cell Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity

BackgroundMutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial...Full Text Available

Regulation of life span by mitochondrial respiration: the HIF-1 and ROS connection

SummaryThe life span of C. elegans can be increased via reduced function of the mitochondria; however, the extent to which mitochondrial alteration in a single,...Full Text Available

2011-01-07

Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants

A mild reduction in mitochondrial respiration extends the life span of many species, including C. elegans. We recently showed that hypoxia-inducible factor 1 (HIF-1) is required for...Full Text Available

Gene expression profiling of oxidative stress response of C. elegans aging defective AMPK mutants using massively parallel transcriptome sequencing

Many lifespan-modulating genes are involved in either generation of oxidative substrates and end-products, or their detoxification and removal. Among such metabolites, only lipoperoxides have the ability...Full Text Available

Biochemical analysis of PIFTC3, the Trypanosoma brucei ortholog of nematode DYF-13, reveals interactions with established and putative intraflagellar transport components

BackgroundA strong association between stress resistance and longevity in multicellular organisms has been established as many mutations that extend lifespan also show increased...Full Text Available

Absence of Ataxin-3 Leads to Enhanced Stress Response in C. elegans

DYF-13, originally identified in C. elegans within a collection of dye-filling chemosensory mutants, is one of several proteins that have been classified as putatively involved...Full Text Available

2010-10-01

A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding

Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein...Full Text Available

Vitamin D and respiratory health

BackgroundProteins may evolve through the recruitment and modification of discrete domains, and in many cases, protein action can be dissected at the domain level. PDZ domains are...Full Text Available

Transcriptional Regulation of Membrane Lipid Homeostasis in Escherichia coli*

Vitamin D is now known to be of physiological importance outside of bone health and calcium homeostasis, and there is mounting evidence that it plays a beneficial role in the prevention and/or treatment...Full Text Available

2009-10-01

The hepcidin-binding site on ferroportin is evolutionarily conserved

The biophysical properties of membrane phospholipids are controlled by the composition of their constituent fatty acids and are tightly regulated in Escherichia...Full Text Available

2009-12-11

Hypothalamic and dietary control of temperature-mediated longevity

SummaryMammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to...Full Text Available

2008-08-01

Fractal dynamics in physiology: Alterations with disease and aging

Temperature is an important modulator of longevity and aging in both poikilotherms and homeotherm animals. In homeotherms, temperature homeostasis is regulated primarily in the preoptic area...Full Text Available

2010-01-01

Cellular and Molecular Mechanisms of Bone Remodeling*

According to classical concepts of physiologic control, healthy systems are self-regulated to reduce variability and maintain physiologic constancy. Contrary to the predictions of homeostasis, however,...Full Text Available

2002-02-19

1 2 3 4 5

APOPTOSIS BY DIETARY AGENTS FOR PREVENTION AND TREATMENT OF CANCER

Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to...Full Text Available

2010-08-13

A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in a-synuclein transgenic C. elegans

The role of apoptosis or programmed cell death in the regulation of development and maintenance of homeostasis in multicellular organisms is well established. During the last decade, naturally...Full Text Available

2008-12-01

British Library Electronic Table of Contents (United Kingdom)

Mutations or multiplications in a-synuclein gene cause familial forms of Parkinson disease or dementia with Lewy bodies (LB), and the deposition of wild-type a-synuclein as LB occurs as a hallmark lesion of these disorders, collectively referred to as synucleinopathies, implicating a-synuclein in the pathogenesis of synucleinopathy. To identify modifier genes of a-synuclein-induced neurotoxicity, we conducted an RNAi screen in transgenic C. elegans (Tg worms) that overexpress human a-synuclein in a pan-neuronal manner. To enhance the RNAi effect in neurons, we crossed a-synuclein Tg worms with an RNAi-enhanced mutant eri-1 strain. We tested RNAi of 1673 genes related to nervous system or synaptic functions, and identified 10 genes that, upon knockdown, caused severe growth/motor abnormalit...

2008-01-01

The prooxidant-antioxidant homeostasis in Guinea pigs after exposure to fractionated low-low X-radiation and correction of its disturbances with antioxidant complex treatment

Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis

The state of prooxidant-antioxidant homeostasis in Guinea pigs exposed to whole-body fractionated X-irradiation (5 fractions of 0.2 Gy at a 24 hr interval, up to total dose of 1.0 Gy, at a dose rate of 0.425 R/min) and a possibility of its disturbance correction with the complex of vitamins C, E and P was studied. Accumulation of primary and secondary lipid peroxidation products, decrease of the ascorbic acid content, increase of the content of its oxidized forms (dehydroascorbic acid and diketogulonic acid) in radiosensitive and radioresistant organs were found. Antioxidant complex administration reduced the disturbances of prooxidant-antioxidant homeostasis, but did not provide complete normalization.

Transplantation of allogeneic T cells alters iron homeostasis in NOD/SCID mice

Wiskott-Aldrich syndrome protein (WASp) is essential for optimal T cell activation. Patients with WAS exhibit both immunodeficiency and a marked susceptibility to systemic autoimmunity. We investigated...Full Text Available

2007-02-01

The orphan nuclear receptor small heterodimer partner mediates male infertility induced by diethylstilbestrol in mice

Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT), but the mechanisms leading to overload are unknown. Here, we determined iron levels and the expression...Full Text Available

2009-02-19

The long lifespan of two bat species is correlated with resistance to protein oxidation and enhanced protein homeostasis

Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen...Full Text Available

2009-12-01

The frequency of CD25+CD4+ and FOXP3+ regulatory T cells in ectopic endometrium and ectopic decidua

Altered structure, and hence function, of cellular macromolecules caused by oxidation can contribute to loss of physiological function with age. Here, we tested whether the lifespan of bats, which generally...Full Text Available

2009-07-01

The Receptor Tyrosine Kinase FGFR4 Negatively Regulates NF-kappaB Signaling

BackgroundThe presence of regulatory T (Treg) cells in human endometrium is crucial for maintaining immunological homeostasis within the uterus. For this study we decided to evaluate...Full Text Available

RasGrf1 deficiency delays aging in mice

BackgroundNFκB signaling is of paramount importance in the regulation of apoptosis, proliferation, and inflammatory responses during human development and homeostasis, as...Full Text Available

Rapid, reversible activation of AgRP neurons drives feeding behavior in mice

RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging,...Full Text Available

Molecular Identification and Expression Analysis of Filaggrin-2, a Member of the S100 Fused-Type Protein Family

Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the...Full Text Available

2011-04-01

Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1

Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions....Full Text Available

Mapping of the transcription start site (TSS) and identification of SNPs in the bovine neuropeptide Y (NPY) gene

BackgroundCalcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5-tris-phosphate-induced...Full Text Available

Intrinsic near-24-h pacemaker period determines limits of circadian entrainment to a weak synchronizer in humans

BackgroundNeuropeptide Y is a key neurotransmitter of the central nervous system which plays a vital role in the feed energy homeostasis in mammals. Mutations in the regulatory and...Full Text Available

Hypertrophy and Heart Failure in Mice Overexpressing the Cardiac Sodium-Calcium Exchanger

Endogenous circadian clocks are robust regulators of physiology and behavior. Synchronization or entrainment of biological clocks to environmental time is adaptive and important for physiological homeostasis...Full Text Available

2001-11-20

Homeostasis of intrinsic excitability in hippocampal neurones: dynamics and mechanism of the response to chronic depolarization

Background:The cardiac sodium–calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. Since heart failure...Full Text Available

2007-05-01

Hair Mercury Negatively Correlates with Calcium Pump Activity in Human Term Newborns and Their Mothers at Delivery

In order to maintain stable functionality in the face of continually changing input, neurones in the CNS must dynamically modulate their electrical characteristics. It has been hypothesized that in...Full Text Available

2010-01-01

Effect of Anionic Salt and Highly Fermentable Carbohydrate Supplementations on Urine pH and on Experimentally Induced Hypocalcaemia in Cows

BackgroundCalcium homeostasis is a known target of several environmental toxicants including lead and mercury.ObjectiveOur goal was to determine...Full Text Available

2008-02-01

Discovering Networks of Perturbed Biological Processes in Hepatocyte Cultures

The objective of this experiment was to determine the effect of dietary grain on calcium homeostasis. Six rumen-fistulated dairy cows with 3 or more previous lactations and no history of parturient...Full Text Available

2004-01-01

1 2 3 4 5

Defining the Specificity of Cotranslationally Acting Chaperones by Systematic Analysis of mRNAs Associated with Ribosome-Nascent Chain Complexes

The liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs...Full Text Available

Conditional deletion of Abca3 in alveolar type II cells alters surfactant homeostasis in newborn and adult mice

Polypeptides exiting the ribosome must fold and assemble in the crowded environment of the cell. Chaperones and other protein homeostasis factors interact with newly translated polypeptides to facilitate...Full Text Available

2011-07-01

Computational simulation of vasopressin secretion using a rat model of the water and electrolyte homeostasis

ATP-binding cassette A3 (ABCA3) is a lipid transport protein required for synthesis and storage of pulmonary surfactant in type II cells in the alveoli. Abca3 was conditionally deleted...Full Text Available

2010-05-01

Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis.

BackgroundIn mammals, vasopressin (AVP) is released from magnocellular neurons of the hypothalamus when osmotic pressure exceeds a fixed set-point. AVP participates to the hydromineral...Full Text Available

Age-dependent changes in Ca²⁺ homeostasis in peripheral neurones: implications for changes in function

Cellular cholesterol homeostasis is controlled by sterol-regulated proteolysis of membrane-bound transcription factors called sterol-regulatory element binding proteins (SREBPs). CPP32, a cysteine protease,...Full Text Available

1996-03-01

Acute atrial arrhythmogenicity and altered Ca²⁺ homeostasis in murine RyR2-P2328S hearts

Calcium ions represent universal second messengers within neuronal cells integrating multiple cellular functions, such as release of neurotransmitters, gene expression, proliferation, excitability,...Full Text Available

2007-06-01

ATG12 Conjugation to ATG3 Regulates Mitochondrial Homeostasis and Cell Death

AimsThe experiments explored for atrial arrhythmogenesis and its possible physiological background in recently developed hetero-(RyR2^+/S) and homozygotic...Full Text Available

2011-03-01

Prostaglandin E₂ Signals Through PTGER2 to Regulate Sclerostin Expression

SUMMARYATG12, an ubiquitin-like modifier required for macroautophagy, has a single known conjugation target, another autophagy regulator called ATG5. Here, we identify ATG3 as...Full Text Available

2010-08-20

Molecular recognition of nitrated fatty acids by PPAR[gamma

The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations...Full Text Available

An activated renin-angiotensin system maintains normal blood pressure in aryl hydrocarbon receptor heterozygous mice but not in null mice

Peroxisome proliferator activated receptor-{gamma} (PPAR{gamma}) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPAR{gamma} ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPAR{gamma}. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPAR{gamma} discrimination of various naturally occurring fatty acid derivatives.

2010-03-08

Overview of macroautophagy regulation in mammalian cells

It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr^−/−) mice may alter cardiovascular homeostasis in adulthood....Full Text Available

2010-07-15

British Library Electronic Table of Contents (United Kingdom)

Macroautophagy is a multistep, vacuolar, degradation pathway terminating in the lysosomal compartment, and it is of fundamental importance in tissue homeostasis. In this review, we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes, which are double-membrane-bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes. In most cases, this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway. The discovery of AuTophaGy-related genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation, and there has also been progress in the understanding of molecular aspects of autophagosome maturation. Finally, the regulation of au...

2010-01-01

Long non-coding RNAs in nervous system function and disease

British Library Electronic Table of Contents (United Kingdom)

Central nervous system (CNS) development, homeostasis, stress responses, and plasticity are all mediated by epigenetic mechanisms that modulate gene expression and promote selective deployment of functional gene networks in response to complex profiles of interoceptive and environmental signals. Thus, not surprisingly, disruptions of these epigenetic processes are implicated in the pathogenesis of a spectrum of neurological and psychiatric diseases. Epigenetic mechanisms involve chromatin remodeling by relatively generic complexes that catalyze DNA methylation and various types of histone modifications. There is increasing evidence that these complexes are directed to their sites of action by long non-protein-coding RNAs (lncRNAs), of which there are tens if not hundreds of thousands speci...

2010-01-01

Proving Stabilization of Biological Systems

[Changes in kidney function and the cortisol and ADH levels after peritoneal dialysis with 5% glucose in dogs].

We describe an efficient procedure for proving stabilization of biological systems modeled as qualitative networks or genetic regulatory networks. For scalability, our procedure uses modular proof techniques, where state-space exploration is applied only locally to small pieces of the system rather than the entire system as a whole. Our procedure exploits the observation that, in practice, the form of modular proofs can be restricted to a very limited set. For completeness, our technique falls back on a non-compositional counterexample search. Using our new procedure, we have solved a number of challenging published examples, including: a 3-D model of the mammalian epidermis; a model of metabolic networks operating in type-2 diabetes; a model of fate determination of vulval precursor cells in the C. elegans worm; and a model of pair-rule regulation during segmentation in the Drosophila embryo. Our results show many orders of magnitude speedup in cases where ...

2011-01-01

Studies on adjuvant parenteral nutrition during chemotherapeutic and radiotherapeutic measures in haematological disorders

The authors made peritoneal dialisis with 5% of glucose (7 ml/kg of body weight) in 11 dogs under the conditions of an acute experiments. They examined cortiosl and ADH activity, hematocrite and plasma protein in the samples of blood, obtained on the 20th and 50th minute. ADH was titrated biologicaly by a new method, proposed by Nacev. The results were compared with the changes in the circulatory and renal indices, obtained at the same procedure in the preceding investigations. There was an increase in the cortisol and ADH activity, which could be explained by the total hypovolemia, induced by peritoneal dialisis. The increase of the cortisol level is described as a separate link in a more complex mechanism, assuring metabolic homeostasis. PMID:1222705

1975-01-01

Rapamycin (sirolimus) protects against hypoxic damage in primary heart cultures via Na^+/Ca^2^+ exchanger activation

In patients subjected to bone marrow transplantation the aggressive measures necessarily preceding this treatment lead to drastic metabolic changes which, in turn, are a cause of marked disturbances of homeostasis. The general preparatory measures in the form of cytoreduction by cytostatic drugs are broadened for leukaemic patients to include wholebody irradiation. During the study described here investigations were carried out into the resulting strain on the metabolism. One of the most essential changes observed in those patients was a nitrogen loss of up to approx. 20 g/day that occurred during the immunosuppressive phase. This was accompanied by markedly pronounced variations in fluid elimination, which partly were of an iatrogenic nature. An immediate and sufficient substitution of amino acids in connection with complete parenteral nutrition rapidly acted to compensate for the nitrogen losses, even though these could not be totally reversed to achieve a ...

British Library Electronic Table of Contents (United Kingdom)

Aims: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Rapamycin confers preconditioning-like protection against ischemic-reperfusion injury in isolated mouse heart cultures. Our aim was to further define the role of rapamycin in intracellular Ca^2^+ homeostasis and to investigate the mechanism by which rapamycin protects cardiomyocytes from hypoxic damage. Main methods: We demonstrate here that rapamycin protects rat heart cultures from hypoxic-reoxygenation (H/R) damage, as revealed by assays of lactate dehydrogenase (LDH) and creatine kinase (CK) leakage to the medium, by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-d...

2011-01-01

Physiologically Based Pharmacokinetic Modeling of Fetal and Neonatal Manganese Exposure in Humans: Describing Manganese Homeostasis during Development

British Library Electronic Table of Contents (United Kingdom)

Concerns for potential vulnerability to manganese (Mn) neurotoxicity during fetal and neonatal development have been raised due to increased needs for Mn for normal growth, different sources of exposure to Mn, and pharmacokinetic differences between the young and adults. A physiologically based pharmacokinetic (PBPK) model for Mn during human gestation and lactation was developed to predict Mn in fetal and neonatal brain using a parallelogram approach based upon extrapolation across life stages in rats and cross-species extrapolation to humans. Based on the rodent modeling, key physiological processes controlling Mn kinetics during gestation and lactation were incorporated, including alterations in Mn uptake, excretion, tissue-specific distributions, and placental and lactational transfer ...

2011-01-01

Knowledge-Based Identification of the ERK2/STAT3 Signal Pathway as a Therapeutic Target for Type 2 Diabetes and Drug Discovery

British Library Electronic Table of Contents (United Kingdom)

Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...

2011-01-01

Increased intracellular calcium concentration causes electrical turbulence in guinea pig ventricular myocytes

British Library Electronic Table of Contents (United Kingdom)

Dysregulation of intracellular Ca2+ homeostasis is associated with various pathological conditions and arrhythmogenesis of the heart. The objective of this study was to investigate the effects of an acute increase in intracellular Ca2+ concentration ([Ca2+]i) on the electrophysiology of ventricular myocytes by mimicking intracellular Ca2+ overload. The [Ca2+]i was clamped to either a controlled (65?100 nmol L?1) or increased (1 ?mol L?1) level. The transmembrane action potentials and ionic currents were recorded using whole-cell patch clamp techniques. We found that the acute increase in [Ca2+]i shortened the action potential duration, reduced the action potential amplitude, maximum depolarization velocity and resting membrane potential, caused delayed after-depolarizations (DADs), and tri...

2011-01-01

1 2 3 4 5

Honokiol enhances adipocyte differentiation by potentiating insulin signaling in 3T3-L1 preadipocytes

British Library Electronic Table of Contents (United Kingdom)

Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drug target for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with r...

2011-01-01

Growth factor signalling in the regulation of -cell fate

British Library Electronic Table of Contents (United Kingdom)

Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic -cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring -cells are emerging as central modulator(s) of -cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the -cell-specific insulin receptor knockout (IRKO) mouse manifests hypersecretion of glucagon in the postprandial stag...

2011-01-01

Brain glucose sensing and neural regulation of insulin and glucagon secretion

British Library Electronic Table of Contents (United Kingdom)

Glucose homeostasis requires the tight regulation of glucose utilization by liver, muscle and white or brown fat, and glucose production and release in the blood by liver. The major goal of maintaining glycemia at -5 mM is to ensure a sufficient flux of glucose to the brain, which depends mostly on this nutrient as a source of metabolic energy. This homeostatic process is controlled by hormones, mainly glucagon and insulin, and by autonomic nervous activities that control the metabolic state of liver, muscle and fat tissue but also the secretory activity of the endocrine pancreas. Activation or inhibition of the sympathetic or parasympathetic branches of the autonomic nervous systems are controlled by glucose-excited or glucose-inhibited neurons located at different anatomical sites, mainl...

2011-01-01

Apelin, diabetes, and obesity

British Library Electronic Table of Contents (United Kingdom)

Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not...

2011-01-01

The neuroimmune-endocrine axis: pathophysiological implications for the central nervous system cytokines and hypothalamus-pituitary-adrenal hormone dynamics

Scientific Electronic Library Online (English)

Abstract in english Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are e (more) xpressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms ...

2000-10-01

Prolonged swimming exercise training induce hypophosphatemic osteopenia in stroke-prone spontaneously hypertensive rats (SHRSP).

Natriuretic peptides in the pathophysiology of congestive heart failure.

Stroke-prone spontaneously hypertensive rats (SHRSP) induce spontaneous osteoporosis. To elucidate the specific characteristics of bone metabolism, the SHRSP was compared with age matched Wistar-Kyoto (WKY) rats. We investigated the effects of prolonged swimming exercise training on bone mineral density (BMD) and metabolism in the SHRSP. Seven-week-old male SHRSP and WKY were divided into three groups; the sedentary control WKY group (n = 6, WKY), the sedentary control SHRSP group (n = 6, SP) and the swimming exercise training SHRSP group (n = 6, SWIM) (in pool with 60 min./day, 5 days/week for 12 weeks). The femoral BMD, bone mineral content (BMC), strength, Ca and P contents (%) of SHRSP were approximately 17, 27, 25, 20 and 9%, respectively, lower than that of WKY (p swimming exercise training in the SHRSP induces more cruelly hypophosphatemia, and leading to osteopenia eventually. We conclude that SHRSP induces osteopenia with disturbance of phosphate ...

2000-11-01

Ion movements in cell death: from protection to execution

A hallmark of congestive heart failure (CHF) is the activation of the cardiac endocrine system, in particular atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. ANP and BNP are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilatation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor. All three peptides are cleared by the natriuretic peptide-C receptor and degraded by the ectoenzyme neutral endopeptidase 24.11, both of which are ...

2000-05-01

Scientific Electronic Library Online (English)

Abstract in english Cell death is preceded by severe disruption of inorganic ion homeostasis. Seconds to minutes after an injury, calcium, protons, sodium, potassium and chloride are exchanged between the cell and its environment. Simultaneously, ions are shifted between membrane compartments inside the cell, whereby mitochondria and endoplasmic reticulum play a crucial role. Depending of the type and severity of injury, two mutually exclusive metastable states can be reached, which predict (more) the final outcome. Cells characterized by large increases in cytosolic [Ca2+], [Na+]; and [Mg2+] swell and die by necrosis; alternatively, cells characterized by high [H+]and low [K+], with normal [Na+] and normal to moderate [Ca2+] increases die by apoptosis. The levels of these ions represent central determinants in signaling events leading to cell death. Their movements are explained mechanistically by specific modulation of membrane transport proteins including ...

2002-01-01

Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

Angiogenic cytokines and growth factors in systemic sclerosis.

The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a ...

1988-01-01

Structural and Biochemical Basis for the Binding Selectivity of Peroxisome Proliferator-activated Receptor [gamma] to PGC-1[alpha

Systemic sclerosis is an autoimmune connective tissue disorder characterized by a widespread microangiopathy, autoimmunity and fibrosis of the skin and of various internal organs. Microangiopathy is characterized by a reduced capillary density and an irregular chaotic architecture that lead to chronic tissue hypoxia. Despite the hypoxic conditions, there is no evidence for a sufficient compensative angiogenesis in SSc. Furthermore, vasculogenesis is also impaired. An imbalance between angiogenic and angiostatic factors might explain the pathogenetic mechanisms of SSc vasculopathy. As far as angiogenic factors are concerned, within the most important are vascular endothelial growth factor (VEGF) and its receptors, platelet derived growth factor (PDGF), transforming growth factor beta (TGF-?), fibroblast growth factor -2 (FGF-2), angiopoietin 1 (Ang-1), stromal cell-derived factor 1 (SDF-1/CXCL12), endothelin-1 (ET-1), monocyte chemoattractant protein -1 (MCP-1), urokinase type ...

2011-04-28

Natriuretic peptides in vascular physiology and pathology.

The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and PPAR{gamma} is mediated through both hydrophobic and specific ...

2008-07-23

Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase

Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide receptor (NPR-B), and type C natriuretic ...

2008-01-01

Modeling marrow damage from response data: Morphallaxis from radiation biology to benzene toxicity

By catalyzing the rate-limiting step in adipose tissue lipolysis, hormone-sensitive lipase (HSL) is an important regulator of energy homeostasis. The role and importance of HSL in tissues other than adipose are poorly understood. We report here the cloning and expression of a testicular isoform, designated HSL{sub tes}. Due to an addition of amino acids at the NH{sub 2}-termini, rat and human HSL{sub tes} consist of 1068 and 1076 amino acids, respectively, compared to the 768 and 775 amino acids, respectively, of the adipocyte isoform (HSL{sub adi}). A novel exon of 1.2 kb, encoding the human testis-specific amino acids, was isolated and mapped to the HSL gene, 16 kb upstream of the exons encoding HSL{sub adi}. The transcribed mRNA of 3.9 kb was specifically expressed in testis. No significant similarity with other known proteins was found for the testis-specific sequence. The amino acid composition differs from the HSL{sub adi} sequence, with a notable hydrophilic ...

1996-08-01

Liver Zn-thionein (ZnMT) regulates the interaction of Zn and Pb with delta-aminolevulinic acid dehydratase (ALAD)

Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal ...

1995-12-01

Impaired neonatal survival of pro-opiomelanocortin null mutants.

ZnMT has been postulated to function in essential metal homeostasis and metal detoxication. This study was undertaken to evaluate the potential of liver ZnMT to mediate the interaction of Zn and Pb with the Zn metalloenzyme, ALAD. Pretreatment of rats with Zn activated liver ALAD and attenuated the inhibition of ALAD by Pb in vitro and in vivo. Liver cytosol from Zn-pretreated rats injected with /sup 203/Pb was fractionated via gel filtration and anion-exchange chromatography and disclosed that both Zn and /sup 203/Pb co-eluted in the MT fractions. Both purified ZnMT-I and ZnMT-II bound /sup 203/Pb in vitro as shown by gel filtration chromatography. Addition of purified liver ZnMT to purified bovine liver ALAD reaction mixtures increased enzyme activity by 2-fold and prevented inhibition of ALAD by Pb. Addition of apothionein alone decreased the activity of Zn-activated ALAD and also attenuated Pb inhibition of the enzyme. Gel filtration studies of incubates ...

1987-05-01

Crystal Structure of Human Senescence Marker Protein 30: Insights Linking Structural, Enzymatic, and Physiological Functions

Intercrosses of heterozygous pro-opiomelanocortin (POMC) mice result in homozygous null progeny at lower frequencies than expected. Genotyping offspring at pre-, peri-, and postnatal stages revealed that over half of homozygous null mutants die in the early postnatal stages. To investigate the reasons for this early postnatal lethality, we analyzed in detail different parameters in the initial hours after birth. POMC null mutants born to heterozygous dams presented at birth with corticosterone levels no different from wildtype littermates, were euglycemic, and had normal liver glycogen stores. However, already 30 min after birth corticosterone levels dropped by 80% and were undetectable thereafter, while corticosterone levels in wildtype animals increased during postnatal hours. Circulating adrenaline was almost below detection 1h after birth. Blood glucose levels fell sharply in all genotypes within 30 min after birth; however, wildtype and heterozygous pups overcame hypoglycemia ...

2010-12-22

Age and body mass index-dependent relationship between correction of iron deficiency anemia and insulin resistance in non-diabetic premenopausal women

Human senescence marker protein 30 (SMP30), which functions enzymatically as a lactonase, hydrolyzes various carbohydrate lactones. The penultimate step in vitamin-C biosynthesis is catalyzed by this enzyme in nonprimate mammals. It has also been implicated as an organophosphate hydrolase, with the ability to hydrolyze diisopropyl phosphofluoridate and other nerve agents. SMP30 was originally identified as an aging marker protein, whose expression decreased androgen independently in aging cells. SMP30 is also referred to as regucalcin and has been suggested to have functions in calcium homeostasis. The crystal structure of the human enzyme has been solved from X-ray diffraction data collected to a resolution of 1.4 {angstrom}. The protein has a 6-bladed {beta}-propeller fold, and it contains a single metal ion. Crystal structures have been solved with the metal site bound with either a Ca{sup 2+} or a Zn{sup 2+} atom. The catalytic role of the metal ion has been ...

2010-05-25

The genetic basis of salinity tolerance in Arctic charr (Salvelinus alpinus).

No prospective studies have evaluated the effects of correction of iron deficiency anemia on insulin resistance in non-diabetic premenopausal women with iron deficiency anemia. All patients were treated with oral iron preparations. Insulin resistance was calculated with the Homeostasis Model Assessment formula. All patients were dichotomized by the median for age and BMI to assess how the relationship between iron deficiency anemia and insulin resistance was affected by the age and BMI. Although the fasting glucose levels did not change meaningfully, statistically significant decreases were found in fasting insulin levels following anemia treatment both in the younger age (<40 years) (P=0.40) women and in the low BMI (27 kg/m) (P=0.22) subgroups but not in the older age (>= 40 years) and the high BMI (>-27Kg/m) subgroups. Post-treatment fasting insulin levels were positively correlated both with BMI (r=0.386, P=0.004) and post-treatment hemoglobin levels. ...

ABSTRACT: BACKGROUND: The capacity to maintain internal ion homeostasis amidst changing conditions is particularly important for teleost fishes whose reproductive cycle is dependent upon movement from freshwater to seawater. Although the physiology of seawater osmoregulation in mitochondria-rich cells of fish gill epithelium is well understood, less is known about the underlying causes of inter- and intraspecific variation in salinity tolerance. We used a genome-scan approach in Arctic charr (Salvelinus alpinus) to map quantitative trait loci (QTL) correlated with variation in four salinity tolerance performance traits and six body size traits. Comparative genomics approaches allowed us to infer whether allelic variation at candidate gene loci (e.g., ATP1alpha1b, NKCC1, CFTR, and cldn10e) could have underlain observed variation. RESULTS: Combined parental analyses yielded genome-wide significant QTL on linkage groups 8, 14 and 20 for salinity tolerance performance ...

2011-09-21

100