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Sample records for atractyloside

  1. Interaction of ADP, atractyloside, and gummiferin on the ADP translocase of the inner mitochondrial membrane

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    Vignais, P.V.; Vignais, P.M.; Defaye, G.; Lauquin, G.; Doussiere, J.; Chabert, J.; Brandolin, G.

    1972-05-01

    From international conference on mechanism in bioenergetica; Bari, Italy (1 May 1972). Two specific inhibitors of the adenine nucleotide translocation, gummiferin (GUM), identified to 4-carboxyatractyloside and atractyloside (ATR), were labeled with /sup 35/S and their binding properties to whole mitochondria and inner mitochondrial membrane vesicles used to monitor changes of membrane conformation induced by ADP. (auth)

  2. Study of composition of espresso coffee prepared from various roast degrees of Coffea arabica L. coffee beans.

    Science.gov (United States)

    Kučera, Lukáš; Papoušek, Roman; Kurka, Ondřej; Barták, Petr; Bednář, Petr

    2016-05-15

    Espresso coffee samples prepared at various roasting degrees defined according to its basic conventional classification (light, medium, medium-dark and dark roasted) were analyzed by ultra-performance liquid chromatography/tandem mass spectrometry. Obtained raw data were processed using multivariate statistical analysis (Principal Component Analysis, PCA) to evaluate chemical differences between each roasting degrees (untargeted part of study). All four roasting degrees were resolved in appropriate Score plot. Orthogonal Projections to Latent Structures provided signals of significant markers describing the differences among particular roasting degrees. Detailed interpretation of those signals by targeted LC/MS(2) analysis revealed four groups of compounds. The first two groups involve chlorogenic acids and related lactones. The signals of other two sets of markers were ascribed to some specific atractylosides and particular melanoidins. Ratios of contents of selected representatives of each group to the sum of all identified markers were proposed as definite parameters for determination of roasting degree of Brazilian coffee Arabica.

  3. Arsenate uncoupling of oxidative phosphorylation in isolated plant mitochondria

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    Wickes, W.A.; Wiskich, J.T.

    1976-01-01

    The uncoupling by arsenate of beetroot and cauliflower bud mitochondria showed the following characteristics: arsenate stimulation of respiration above the rate found with phosphate; inhibition of arsenate-stimulated respiration by phosphate; enhancement of arsenate-stimulated respiration by ADP; only partial prevention of this ADP-enhanced respiration by atractyloside; inhibition by oligomycin of the arsenate-stimulated respiration back to the phosphate rate; and the absence of any stimulatory effect of ADP in the presence of oligomycin. These results are qualitatively analogous to those reported for arsenate uncoupling in rat liver mitochondria. Arsenate stimulated malate oxidation, presumably by stimulating malate entry, in both beetroot and cauliflower bud mitochondria; however, high rates of oxidation, and presumably entry, were only sustained with arsenate in beetroot mitochondria. NADH was oxidized rapidly in cauliflower bud mitochondria in the presence of arsenate, showing that arsenate did not inhibit electron transfer processes.

  4. Superstoichiometric Ca2+ uptake supported by hydrolysis of endogenous ATP in rat liver mitochondria.

    Science.gov (United States)

    Brand, M D; Lehninger, A L

    1975-10-10

    The nature of the energy store causing rapid superstoichiometric leads to H+/2e minus ejection and leads to Ca2+/2e minus uptake ratios in rat liver mitochondria pulsed with Ca2+ has been investigated. The extent and the rate of the initial fast superstoichiometric phase of H plus ejection were greatly reduced by oligomycin and other ATPase inhibitors; the subsequent shoichiometric phase was unaffected. No such inhibition was seen with atractyloside. Similarly, the initial fast phase of Ca2+ uptake was reduced in extent by oligomycin, whereas the slower stoichiometric phase was unaffected. Moreover, the ATP content of mitochondria previously incubated with succinate decreased by about 80% within 5 s after pulsing with Ca2+. The energy store for superstoichiometric Ca2+ uptake and H plus injection is thus identified as endogenous ATP.

  5. Protection of Astragaloside Derivate on Oxidative Stress and Hypertrophy in Cardiomyocytes

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    HAO Chun-hua; WANG Wei-ting; ZHAO Zhuan-you; TANG Li-da

    2011-01-01

    Objective The astragaloside Ⅳ(ASI)has been proved to play an important role in protecting against cell death on cardiovascular diseases.This study aims to investigate the effect of the astragaloside derivate.(ASId)on confronting oxidative stress and hypertrophy in myocardial cells.Methods Following exposure embryonic rat cardiac H9c2 cells to hydrogen peroxide(H2O2)and angiotensin Ⅱ for developing oxidative stress and hypertrophy,ASId at final concentrations(0.1,1,and 10 μmol/L)was added to study its role in protecting cardiomyocytes by biochemical detection and cell size measurement In addition,the mitochondrial permeability transition pore(mPTP)opener atractyloside(20 μmol/L)and inhibitor cyclosporin A(CSA)(1 μmol/L)were employed to investigate the possible mechanisms for anti-oxidation.Results ASId at 1 and 10 μmol/L in cultures suppressed oxidative stress at different degrees,which induced the decrease in LDH activity and MDA content,and also the increase in SOD activity in comparable with the model group; The mPTP opener atractyloside and inhibitor CSA weakened and strengthened the role of ASId,respectively.ASId at 10 μmol/L inhibited cell hypertrophy,and the cell diameter,surface area,and protein content were all decreased in comparable of those cells in model group.Conclusion ASId is involved in the cytoprotective effects on oxidative stress through a pathway mediated by mPTP,and also has a protective effect against hypertrophy.

  6. Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    YAO Yun-tai; FANG Neng-xin; SHI Chun-xia; LI Li-huan

    2010-01-01

    Background Studies suggested that anesthetics administered upon the early reperfusion or "anesthetic postconditioning" could protect post-ischemic hearts against myocardial ischemia reperfusion injury (MIRI).However, the mechanism responsible for such protection was not well-elucidated.We investigated the cardioprotection induced by sevoflurane postconditioning (SpostC) in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase 1 and 2 (ERK 1/2), mitochondrial KATP channels (mitoKATP) and mitochondrial permeability transition pore (mPTP), by selectively inhibiting PI3K, ERK 1/2, mitoKATP, with LY294002 (LY), PD98059 (PD), 5-hydroxydecanoate (5-HD) and by directly opening of mPTP with atractyloside (ATR), respectively.Methods Isolated rat hearts were randomly assigned to one of the 12 groups (n=15):Time control (continuous perfusion), ISCH (30 minutes of ischemia followed by 60 minutes of reperfusion alone), SpostC (3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia), ISCH+LY,ISCH+PD, ISCH+ATR, ISCH+5-HD and ISCH+ dimethyl sulfoxide (DMSO) groups (LY, PD, ATR, 5-HD and DMSO (the vehicle) was administered respectively during the first 15 minutes of reperfusion following test ischemia), SpostC+LY, SpostC+PD, SpostC+ATR and SpostC+5-HD groups (LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively).Hemodynamics was compared within and between groups.Infarction size was determined at the end of experiments using triphenyltetrazolium chloride (TTC) staining.Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) released from necrotic myocardium, were compared among TC, ISCH and SpostC groups.To investigate the relationships between RISK and mPTP implicated in SpostC, NAD+ content in myocardium, a marker of mPTP opening, was compared among some experimental groups (TC, ISCH, ISCH

  7. Evaluation of the electron transport chain inhibition and uncoupling of mitochondrial bioelectrocatalysis with antibiotics and nitro-based compounds

    Energy Technology Data Exchange (ETDEWEB)

    Arechederra, Marguerite N.; Fischer, Caitlin N.; Wetzel, David J. [Department of Chemistry, Saint Louis University, 3501 Laclede Ave., St. Louis, MO (United States); Minteer, Shelley D., E-mail: minteers@slu.ed [Department of Chemistry, Saint Louis University, 3501 Laclede Ave., St. Louis, MO (United States)

    2010-12-30

    Mitochondrial bioelectrocatalysis can be useful for sensing applications due to the unique metabolic pathways than can be selectively inhibited and uncoupled in mitochondria. This paper details the comparison of different inhibitors and nitro-containing explosive uncouplers in a mitochondria-catalyzed biofuel cell for self-powered explosive sensing. Previous research has reported inhibition of pyruvate oxidation at a mitochondria-modified electrode followed by nitroaromatic uncoupling of current and power. We have previously used oligomycin as the antibiotic and nitrobenzene as the uncoupler of the membrane in the mitochondria-catalyzed biofuel cell, but no comprehensive comparison of various mitochondria inhibitors or explosives has been performed. Results are discussed here for inhibitors targeting complex I, complex III, ATP synthases, adenine nucleotide transport and monocarboxylic acid transport. Reactivation with nitrobenzene was possible in the presence of these inhibitors: oligomycin, 3,3'-diindolylmethane, atractyloside, rotenone, {alpha}-cyano-4-hydroxy cinnamic acid and antimycin A. All eleven explosives studied, including: 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), caused uncoupling of the mitochondria function and could be detected by the biosensor.

  8. Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

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    Carola Stockburger

    2016-01-01

    Full Text Available The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer’s disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

  9. Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

    Science.gov (United States)

    Stockburger, Carola; Miano, Davide; Pallas, Thea; Müller, Walter E.

    2016-01-01

    The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function. PMID:27747106

  10. Evidence that the major metabolites accumulating in medium-chain acyl-CoA dehydrogenase deficiency disturb mitochondrial energy homeostasis in rat brain.

    Science.gov (United States)

    Schuck, Patrícia Fernanda; Ferreira, Gustavo da Costa; Tonin, Anelise Miotti; Viegas, Carolina Maso; Busanello, Estela Natacha Brandt; Moura, Alana Pimentel; Zanatta, Angela; Klamt, Fábio; Wajner, Moacir

    2009-11-03

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an inherited metabolic disorder of fatty acid oxidation in which the affected patients predominantly present high levels of octanoic (OA) and decanoic (DA) acids and their glycine and carnitine by-products in tissues and body fluids. It is clinically characterized by episodic encephalopathic crises with coma and seizures, as well as by progressive neurological involvement, whose pathophysiology is poorly known. In the present work, we investigated the in vitro effects of OA and DA on various parameters of energy homeostasis in mitochondrial preparations from brain of young rats. We found that OA and DA markedly increased state 4 respiration and diminished state 3 respiration as well as the respiratory control ratio, the mitochondrial membrane potential and the matrix NAD(P)H levels. In addition, DA-elicited increase in oxygen consumption in state 4 respiration was partially prevented by atractyloside, indicating the involvement of the adenine nucleotide translocator. OA and DA also reduced ADP/O ratio, CCCP-stimulated respiration and the activities of respiratory chain complexes. The data indicate that the major accumulating fatty acids in MCADD act as uncouplers of oxidative phosphorylation and as metabolic inhibitors. Furthermore, DA, but not OA, provoked a marked mitochondrial swelling and cytochrome c release from mitochondria, reflecting a permeabilization of the inner mitochondrial membrane. Taken together, these data suggest that OA and DA impair brain mitochondrial energy homeostasis that could underlie at least in part the neuropathology of MCADD.

  11. Transport of calcium ions by Ehrlich ascites-tumour cells.

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    Landry, Y; Lehninger, A L

    1976-08-15

    Ehrlich ascites-tumour cells accumulate Ca2+ when incubated aerobically with succinate, phosphate and rotenone, as revealed by isotopic and atomic-absorption measurements. Ca2+ does not stimulate oxygen consumption by carefully prepared Ehrlich cells, but des so when the cells are placed in a hypo-osmotic medium. Neither glutamate nor malate support Ca2+ uptake in 'intact' Ehrlich cells, nor does the endogenous NAD-linked respiration. Ca2+ uptake is completely dependent on mitochondrial energy-coupling mechansims. It was an unexpected finding that maximal Ca2+ uptake supported by succinate requires rotenone, which blocks oxidation of enogenous NAD-linked substrates. Phosphate functions as co-anion for entry of Ca2+. Ca2+ uptake is also supported by extra-cellular ATP; no other nucleoside 5'-di- or tri-phosphate was active. The accumulation of Ca2+ apparently takes place in the mitochondria, since oligomycin and atractyloside inhibit ATP-supported Ca2+ uptake. Glycolysis does not support Ca2+ uptake. Neither free mitochondria released from disrupted cells nor permeability-damaged cells capable of absorbing Trypan Blue were responsible for any large fraction of the total observed energy-coupled Ca2+ uptake. The observations reported also indicate that electron flow through energy-conserving site 1 promotes Ca2+ release from Ehrlich cells and that extra-cellular ATP increase permeability of the cell membrane, allowing both ATP and Ca2+ to enter the cells more readily.

  12. Modulation of the cardioprotective effect of ischemic preconditioning in hyperlipidaemic rat heart.

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    Yadav, Harlokesh Narayan; Singh, Manjeet; Sharma, Pyare Lal

    2010-09-15

    Ischemic preconditioning (IPC) produces cardioprotection by phosphorylation of glycogen synthaes kinase-3beta (GSK-3beta) that inhibits the opening of mitochondrial permeability transition pore (MPTP), and this cardioprotective action of IPC is attenuated by hyperlipidaemia. The present study investigated the role of GSK-3beta in attenuation of cardioprotective effect of IPC, by hyperlipidaemia in the rat heart. Hyperlipidaemia was produced in rat by feeding high fat diet for six weeks. Isolated perfused rat heart was subjected to 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was analyzed from coronary effluent. IPC significantly decreased the myocardial infarct size and the release of LDH and CK-MB from normal rat heart. IPC induced myocardial protection was attenuated in hyperlipidaemic rat heart. However, cardioprotective effect of pharmacological preconditioning with GSK-3beta inhibitors i.e. Lithium Chloride (LiCl) (20mM), Indirubin - 3 Monooxime (1 microM) and 3-(2, 4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2, 5-dione (SB216763) (3 microM), was not attenuated. This differential attenuation by hyperlipidaemia, of IPC and pharmacological preconditioning induced cardioprotection is a new finding in our study. GSK-3beta inhibition is reported to increase the threshold of opening for MPTP during reperfusion. Administration of atractyloside (20 microM), an opener of MPTP, significantly attenuated the cardioprotective effect of IPC in normal heart, and pharmacological preconditioning in the hyperlipidaemic rat heart. Thus, the attenuation of cardioprotective effect of IPC in hyperlipidaemic heart may be due to inhibition of protective signaling pathways upstream of GSK-3beta and inhibition of opening of MPTP.

  13. Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model

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    Pin-Fang Kang

    2016-01-01

    Full Text Available The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2 when diabetes mellitus (DM rat heart was subjected to ischemia/reperfusion (I/R intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH; cardiomyocyte in high glucose (HG condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker, atractyloside (mitoPTP opener, and wortmannin (PI3K inhibitor groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.

  14. Hypothesis on skeletal muscle aging : mitochondrial adenine nucleotide translocator decreases reactive oxygen species production while preserving coupling efficiency

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    Philippe eDIOLEZ

    2015-12-01

    Full Text Available Mitochondrial membrane potential is the major regulator of mitochondrial functions, including coupling efficiency and production of reactive oxygen species (ROS. Both functions are crucial for cell bioenergetics. We previously presented evidences for a specific modulation of adenine nucleotide translocase (ANT appearing during aging that results in a decrease in membrane potential - and therefore ROS production – but surprisingly increases coupling efficiency under conditions of low ATP turnover. Careful study of the bioenergetic parameters (oxidation and phosphorylation rates, membrane potential of isolated mitochondria from skeletal muscles (gastrocnemius of aged and young rats revealed a remodeling at the level of the phosphorylation system, in the absence of alteration of the inner mitochondrial membrane (uncoupling or respiratory chain complexes regulation. We further observed a decrease in mitochondrial affinity for ADP in aged isolated mitochondria, and higher sensitivity of ANT to its specific inhibitor atractyloside. This age-induced modification of ANT results in an increase in the ADP concentration required to sustain the same ATP turnover as compared to young muscle, and therefore in a lower membrane potential under phosphorylating - in vivo - conditions. Thus, for equivalent ATP turnover (cellular ATP demand, coupling efficiency is even higher in aged muscle mitochondria, due to the down-regulation of inner membrane proton leak caused by the decrease in membrane potential. In the framework of the radical theory of aging, these modifications in ANT function may be the result of oxidative damage caused by intra mitochondrial ROS and may appear like a virtuous circle where ROS induce a mechanism that reduces their production, without causing uncoupling, and even leading in improved efficiency. Because of the importance of ROS as therapeutic targets, this new mechanism deserves further studies.

  15. Liver mitochondrial dysfunction is reverted by insulin-like growth factor II (IGF-II in aging rats

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    Castilla-Cortazar Inma

    2011-07-01

    Full Text Available Abstract Background Serum IGF-I and IGF-II levels decline with age. IGF-I replacement therapy reduces the impact of age in rats. We have recently reported that IGF-II is able to act, in part, as an analogous of IGF-I in aging rats reducing oxidative damage in brain and liver associated with a normalization of antioxidant enzyme activities. Since mitochondria seem to be the most important cellular target of IGF-I, the aim of this work was to investigate whether the cytoprotective actions of IGF-II therapy are mediated by mitochondrial protection. Methods Three groups of rats were included in the experimental protocol young controls (17 weeks old; untreated old rats (103 weeks old; and aging rats (103 weeks old treated with IGF-II (2 μg/100 g body weight and day for 30 days. Results Compared with young controls, untreated old rats showed an increase of oxidative damage in isolated mitochondria with a dysfunction characterized by: reduction of mitochondrial membrane potential (MMP and ATP synthesis and increase of intramitochondrial free radicals production and proton leak rates. In addition, in untreated old rats mitochondrial respiration was not blocked by atractyloside. In accordance, old rats showed an overexpression of the active fragment of caspases 3 and 9 in liver homogenates. IGF-II therapy corrected all of these parameters of mitochondrial dysfunction and reduced activation of caspases. Conclusions The cytoprotective effects of IGF-II are related to mitochondrial protection leading to increased ATP production reducing free radical generation, oxidative damage and apoptosis.

  16. An alternative membrane transport pathway for phosphate and adenine nucleotides in mitochondria and its possible function.

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    Reynafarje, B; Lehninger, A L

    1978-10-01

    This paper describes the properties and a possible biological role of a transport process across the inner membrane of rat liver mitochondria resulting in the exchange of ATP(4-) (out) for ADP(3-) (in) + 0.5 phosphate(2-) (in). This transmembrane exchange reaction, designated as the ATP-ADP-phosphate exchange, is specific for the ligands shown, electroneutral, insensitive to N-ethylmaleimide or mersalyl, inhibited by atractyloside, and appears to occur only in the direction as written. It is thus distinct from the well-known phosphate-hydroxide and phosphate-dicarboxylate exchange systems, which are inhibited by mersalyl, and from the ATP-ADP exchanger, which does not transport phosphate. During ATP hydrolysis by mitochondria, half of the phosphate formed from ATP passes from the matrix to the medium by the mersalyl-insensitive ATP-ADP-phosphate exchange and the other half by the well-known mersalyl-sensitive phosphate-hydroxide exchange. These and other considerations have led to a hypothesis for the pathway and stoichiometry of ATP-dependent reverse electron transport, characterized by a requirement of 1.33 molecules of ATP per pair of electrons reversed and by the utilization of a different membrane transport pathway for phosphate and adenine nucleotides than is taken in forward electron flow and oxidative phosphorylation. The possible occurrence of independent pathways for ATP-forming forward electron flow and ATP-consuming reverse electron flow is consonant with the fact that the opposing degradative and synthetic pathways in the central routes of cell metabolism generally have different pathways that are independently regulated.

  17. Patogênese, sinais clínicos e patologia das doenças causadas por plantas hepatotóxicas em ruminantes e eqüinos no Brasil Pathogenesis, clinical signs and pathology of diseases caused by hepatotoxic plants in ruminants and horses in Brazil

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    Julio Cesar A. Santos

    2008-01-01

    Full Text Available Plantas que causam lesões hepáticas em ruminantes e eqüinos constituem um grupo importante de plantas tóxicas no Brasil. Em geral essas plantas podem ser divididas em três grandes grupos: plantas que causam necrose hepática aguda; plantas que causam fibrose hepática; e plantas que causam fotossensibilização. Em algumas dessas plantas os princípios tóxicos já foram identificados. Das plantas que causam necrose hepática aguda, os carboxiatractilosídeos estão presentes em Cestrum parqui e Xanthium cavanillesi. Os alcalóides pirrolizidínicos estão presentes nas plantas que causam fibrose hepática (Senecio spp., Echium plantagineum, Heliotropum spp. e Crotalaria spp.. Das plantas que causam fotossensibilização hepatógena são conhecidos os furanossesquiterpenos em Myoporum spp., triterpenos em Lantana spp., e saponinas esteroidais em Brachiaria spp. e Panicum spp. O quadro clínicopatológico dessas intoxicações e o mecanismo geral da insuficiência hepática, incluindo meios de diagnóstico, são descritos neste artigo de revisão.Plants causing hepatic lesions in ruminants and horses constitute one important group of poisonous plants in Brazil. These plants can be placed in three major groups: plants causing acute liver necrosis; plants causing liver fibrosis; and plants causing hepatogenous photosensitization. For some of these plants the toxic principles are known. Cestrum parqui and Xanthium cavanillesi that cause acute liver necrosis contain carboxy-atractylosides. Senecio spp., Crotalaria spp., and Echium plantagineum that cause liver fibrosis contain pyrrolizidine alkaloids. As for the group of plants causing hepatogenous photosensibilization, Myoporum spp. contain furanosesquiterpenes, Lantana spp contain triterpenes, and Brachiaria spp. and Panicum spp. contain steroidal saponins. The clinical and pathologic features of the toxicosis caused by these phytotoxins, general mechanisms of production for the production of

  18. 线粒体钙单向转运体对线粒体通透性转换孔的调控作用%Mitochondrial calcium uniporter could regulate mitochondrial permeability transition pore

    Institute of Scientific and Technical Information of China (English)

    吴秀云; 王士雷; 王鹏; 李瑜; 王艳婷; 姚如永; 王黎

    2012-01-01

    目的 探讨原代培养的新生大鼠海马神经元线粒体钙单向转运体(mitochondrial calcium uniporter,MCU)对线粒体通透性转换孔(mitochondrial permeability transition pore,mPTP)是否有调控作用.方法 原代培养的大鼠海马神经元采用随机数字表法分为7组,每组6孔:对照组(Control组)不预先给药;精胺(spermine,Sper)组,检测时给予30μmol/L的Sper;Ru360组检测前30 min给予10 μμmol/L的Ru360;环孢菌素(ciclosporinA,CsA)组检测前30 min给予0.2 μmol/L的CsA;苍术甙(atractyloside,Atr)组检测时给予400 μmol/L的Atr;Ru360+Atr组,检测前30 min给予10 μmol/L的Ru360,检测时给予400μmol/L的Atr; CsA+Sper组,检测前30 min给予0.2μmol/L的CsA,检测时给予30 μmol/L的Sper;建立钙超载模型:各个实验组上机检测时都给予200 μmol/L的CaC12.在激光共聚焦显微镜下持续监测6 min观察各个实验组线粒体酯化钙黄绿素(calcein AM)荧光强度随着时间的变化.结果 对照组线粒体calcein AM荧光强度迅速减低(0.073±0.011);与对照组比较,Ru360组(0.779±0.015)、CsA组(0.923±0.011)线粒体calcein AM荧光强度减低缓慢(P<0.05);与Sper组(0.023±0.006)比较,CsA+Sper组(0.713±0.032)线粒体calcein AM荧光强度减低缓慢(P<0.05);Ru360+Atr组(0.643±0.087)与Atr组(0.047±0.015)比较,线粒体calcein AM荧光强度减低缓慢(P<0.05);与Ru360组(0.779±0.015)比较,Sper组(0.023±0.006)线粒体内calcein AM的荧光强度迅速减低(P<0.05).结论 在体外培养的海马神经元水平上MCU对mPTP有调控作用.%Objective To investigate whether mitochondrial calcium uniporte (MCU) can regulate the mitochondrial permeability transition pore(mPTP) in primary hippocampal neurons. Methods The primary hippocampal hippocampal neurons were randomly divided into seven groups according to the random number table:control group (n=6):without any prior administration,Spermine(Sper) group(n=6):gave 30 μmol/L Sper before the

  19. Hepatic injury induced by carbon dioxide pneumoperitoneum in experimental rats

    Institute of Scientific and Technical Information of China (English)

    Gui-Sen Xu; He-Nian Liu; Jun Li; Xiao-Ling Wu; Xue-Mei Dai; Ying-Hai Liu

    2009-01-01

    AIM: To observe the hepatic injury induced by carbon dioxide pneumoperitoneum in rats and to explore its potential mechanism. METHODS: Thi r ty heal thy male SD rats were randomly divided into control group (n = 10), 0 h experimental group (n = 10) and 1 h experimental group (n = 10) after sham operation with carbon dioxide pneumoperitoneum. Histological changes in liver tissue were observed with hematoxylineosin staining. Liver function was assayed with an automatic biochemical analyzer. Concentration of malonyldialdehyde (MDA) and activity of superoxide dismutase (SOD) were assayed by colorimetry. Activity of adenine nucleotide translocator in liver tissue was detected with the atractyloside-inhibitor stop technique. Expression of hypoxia inducible factor-1 (HIF-1) mRNA in liver tissue was detected with in situ hybridization. RESULTS: Carbon dioxide pneumoperitoneum for 60 min could induce liver injury in rats. Alanine aminotransferase and aspartate aminotransferase were 95.7 ± 7.8 U/L and 86.8 ± 6.9 U/L in 0 h experimental group, and 101.4 ± 9.3 U/L and 106.6 ± 8.7 U/L in 1 h experimental group. However, no significant difference was found in total billirubin, albumin, and pre-albumin in the three groups. In 0 h experimental group, the concentration of MDA was 9.83 ± 2.53 μmol/g in liver homogenate and 7.64 ± 2.19 μmol/g in serum respectively, the activity of SOD was 67.58 ± 9.75 nu/mg in liver and 64.47 ± 10.23 nu/mg in serum respectively. In 1 h experimental group, the concentration of MDA was 16.57 ± 3.45 μmol/g in liver tissue and 12.49 ± 4.21 μmol/g in serum respectively, the activity of SOD was 54.29 ± 7.96 nu/mg in liver tissue and 56.31 ± 9.85 nu/mg in serum, respectively. The activity of ANT in liver tissue was 9.52 ± 1.56 in control group, 6.37 ± 1.33 in 0 h experimental group and 7.28 ± 1.45 (10-9 mol/min per gram protein) in 1 h experimental group, respectively. The expression of HIF-1 mRNA in liver tissue was not detected in

  20. Two clinically relevant pressures of carbon dioxide pneumooperitoneum cause hepatic injury in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    Jun Li; Ying-Hai Liu; Zhan-Yong Ye; He-Nian Liu; Shan Ou; Fu-Zhou Tian

    2011-01-01

    AIM: To observe the hepatic injury induced by carbon dioxide pneumoperitoneum (CDPP) in rabbits, compare the effffects off low- and high-pressure pneumoperitoneum, and to determine the degree off hepatic injury induced by these two clinically relevant CDPP pressures. METHODS: Thirty healthy male New Zealand rabbits weighing 3.0 to 3.5 kg were randomly divided into three groups (n = 10 ffor each group) and subjected to the ffollowing to CDPP pressures: no gas control, 10 mmHg, or 15 mmHg. Histological changes in liver tissues were observed with hematoxylin and eosin staining and transmission electron microscopy. Liver ffunction was evaluated using an automatic biochemical analyzer. Adenine nucleotide translocator (ANT) activity in liver tissue was detected with the atractyloside-inhibitor stop technique. Bax and Bcl-2 expression levels were detected by western blotting. RESULTS: Liver ffunctions in the 10 mmHg and 15 mmHg experimental groups were significantly disturbed compared with the control group. Affter CDPP, the levels off alanine transaminase and aspartate transaminase were 77.3 ± 14.5 IU/L and 60.1 ± 11.4 IU/L, respectively, in the 10 mmHg experimental group and 165.1 ± 19.4 IU/L and 103.8 ± 12.3 IU/L, respectively, in the 15 mmHg experimental group, which were all higher than those off the control group (PP < 0.05). There was no difffference in pre-albumin concentration between the 10 mmHg experimental group and the control group, but the pre-albumin level off the 15 mmHg experimental group was significantly lower than that of the control group (< 0.05). No significant differences were observed in the levels off total bilirubin or albumin among the three groups. Affter 30 and 60 min off CDPP, pH was reduced (PP < 0.05) and PPaCO2 was elevated (< 0.05) in the 10 mmHg group compared with controls, and these changes were more pronounced in the 15 mmHg group. Hematoxylin and eosin staining showed no significant change in liver morphology, except ffor mild

  1. Dexmedetomidine preconditioning protects isolated rat hearts against ischemia/reperfusion injuries and its mechanism%右美托咪定预处理减轻离体大鼠心脏缺血/再灌注损伤的线粒体相关机制

    Institute of Scientific and Technical Information of China (English)

    姜翠翠; 夏满莉; 王敏; 陈士票

    2013-01-01

    Objective:To investigate the protective effect of dexmedetomidine (Dex) preconditioning against ischemia/reperfusion (I/R) injuries in isolated rat hearts and its relation to mitochondrial permeability transition pore (mPTP) and mitochondrial ATP-sensitive K+ channel (mitoKATP).Methods:The hearts of male SD rats were isolated to mount on the Langendorff apparatus and subjected to 30 min global ischemia followed by 120 min reperfusion.The isolated hearts were treated with Dex (10nmol/L) before ischemia for 15 min.The left ventricular hemodynamic parameters,coronary flow (CF)and the lactate dehydrogenase (LDH) release in the coronary effluent at 5 min reperfusion were measured.The formazan content was assayed to determine the myocardial viability at the end of reperfusion.Results:Compared with normal controls,I/R markedly decreased the left ventricular developed pressure and CF during the whole reperfusion period and the formazan content; while the left ventricular end diastolic pressure and LDH release were significantly increased.Dex preconditioning markedly improved the myocardial viability and cardiac function (P <0.01),which were reversed by the treatment with both atractyloside (20 μmol/L before ischemian),an opener of mPTP,and 5-hydroxydecanoate (100 μmol/L at the beginning of repeffusion),an inhibitor of mitoKATP,for 20 min.Conclusion:Dex has protective effect against I/R injuries in isolated rat hearts,which may be related to inhibiting the opening of mPTP at the beginning of reperfusion and activating mitoKATP before ischemia.%目的:研究右美托咪定(dexmedetomidine,Dex)预处理对心肌缺血/再灌注(I/R)损伤的作用及其与线粒体渗透性转换孔(mPTP)和/或线粒体ATP敏感性钾通道(mitoKATP)的关系.方法:分离SD雄性大鼠心脏置于Langendorff系统行全心停灌30 min,再灌注120 min建立心肌I/R损伤模型,停灌前15 min给予Dex(10 nmol/L)处理.测定左心室动力学、再灌注期间冠脉流量及再灌注5

  2. ATP-sensitive potassium channel and mitochondrial permeability transition pore involve in cardioprotection of polydatin%ATP敏感性钾通道和线粒体通透转换孔参与白藜芦醇苷的心肌保护作用

    Institute of Scientific and Technical Information of China (English)

    张利萍; 杨长瑛; 王莹萍; 关玥; 徐瑛; 张翼

    2009-01-01

    AIM To investigate the protective effect of polydatin on ischemia-reperfusion (I-R) injury in cardiac muscle and the possible mechanism. METHODS Langendorff technique was used to make I-R injury in rats. Male Sprague-Dawley rats were randomly divided into control, model, polydatin(25, 50 and 75 μmol·L-1), glibenclamide(Gli, 10 μmol·L-1)+polydatin(50 μmol·L-1), 5-hydroxydecanoate(5-HD, 100 μmol·L-1)+polydatin(50 μmol·L-1), and atractyloside (Atr, 20 μmol·L-1)+polydatin(50 μmol·L-1) groups. The hearts in control group were perfused with K-H solution for 110 min. Model group hearts were subjected to 30 min no-flow global ischemia followed by 60 min of reperfusion. The hearts in 3 polydatin groups were perfused with K-H solution containing different concentrations of polydatin for 10 min before I-R. The hearts in Gli+polydatin and 5-HD+polydatin groups were perfused with K-H solution containing Gli or 5-HD for 5 min firstly, then perfused with K-H solution containing both polydatin and Gli or 5-HD for 10 min before I-R. The hearts in Atr+polydatin group were perfused with K-H solution containing polydatin for 10 min before I-R and perfused with K-H solution containing Atr for 15 min after I-R. The cardiac function, including left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), the maximal rates of rise and decline of left ventricular pressure (±dp/dtmax), and coronary flow (CF), were recorded before, after 30 min no-flow global ischemia and, during 60 min reperfusion. Myocardial infarct size was assessed using 2, 3, 5-triphenyltetrazolium chloride method and myocardial ultrastructure was observed via transmission electron microscope after 60 min reperfusion. RESULTS There were no significant differences in cardiac functional parameters between control and model groups in pre-ischemia condition. Compared with model group, polydatin promoted a better recovery of cardiac function after I-R in a concentration