共查询到20条相似文献,搜索用时 46 毫秒
1.
《Journal of receptor and signal transduction research》2013,33(4):255-278
Estrogen plays a cardioprotective role in female rat hearts subjected to ischemia/reperfusion injury. The its effects are, at least partially, associated with decreased cardiomyocyte contraction and increased expression of β2-adrenoceptor (β2-AR). We tested whether β2-AR could be involved in cardioprotection against ischemic damage and whether the roles of β2-AR were dependent on estrogenic environment. We first determined the effects of hypoxia/reoxygenation (H/R) on cardiomyocyte shortening in female rats. We then determined the roles of β2-AR in cardiomyocyte shortening, lactate dehydrogenase (LDH) release in culture medium, and cell death during hypoxia in isolated myocytes from female rats. We further determined the effects of estrogen on the roles of β2-AR during hypoxia. H/R induced short-term hibernation and stunning at the level of ventricular myocytes from normal female rats. Inhibition of β2-AR with ICI118,551 significantly elevated adrenergic contractile reserve, myocardial injury, and cell death in normal female rats during hypoxia, whereas ovariectomy (OVX) prominently enhanced myocyte contraction, myocardial injury, and cell death, and deprived the alternations in normal female rats. These changes were restored to normal by estrogen replacement (OVX+E2). These data suggest that β2-AR may be involved in the cardioprotection against ischemic damage, and the cardioprotection may depend on estrogenic environment. 相似文献
2.
Wilson HA Allred DV O'Neill K Bell JD 《Apoptosis : an international journal on programmed cell death》2000,5(4):389-396
The purpose of this study was to determine the roles of calcium-dependent phospholipase A2 (cPLA2) and calcium-independent phospholipase A2 (iPLA2) in thapsigargin-induced membrane susceptibility to secretory phospholipase A2 (sPLA2) and programmed cell death. 3H-arachidonic acid release was observed in the presence of thapsigargin. This release was inhibited partially by an inhibitor of iPLA2 (BEL) and completely by an inhibitor of both cPLA2 and iPLA2 (MAFP) suggesting that these enzymes were active during apoptosis. The process of cell death did not require the activity of either enzyme since neither inhibitor impeded the progression of apoptosis. However, both inhibitors increased the susceptibility of the membrane to sPLA2 in the presence of thapsigargin. In the case of BEL, this effect appeared to involve direct induction of apoptosis in a sub-population of the cells independent of the action of iPLA2. In conclusion, the results suggested that cPLA2 and iPLA2 are active during thapsigargin-induced apoptosis in S49 cells and that cPLA2 tempers the tendency of the cells to become susceptible to sPLA2 during apoptosis. 相似文献
3.
The cardioprotective effect of urocortin during ischaemia/reperfusion involves the prevention of mitochondrial damage 总被引:2,自引:0,他引:2
Lawrence KM Townsend PA Davidson SM Carroll CJ Eaton S Hubank M Knight RA Stephanou A Latchman DS 《Biochemical and biophysical research communications》2004,321(2):479-486
We have previously shown, using Affymetrix gene chip technology, that urocortin induces the expression of several diverse genes in cardiac myocytes. An ATP sensitive inwardly rectifying potassium channel, Katp (Kir6.1), the enzyme calcium independent phospholipase A2 (iPLA2), and protein kinase C epsilon (PKCepsilon) and that these genes are involved in the cardioprotective mechanism of action of urocortin. Here we demonstrate that these gene products are localized to cardiac myocyte mitochondria and for the first time show that urocortin protects cardiac myocytes from ischaemia/reperfusion induced cell death by preventing mitochondrial damage. Using pharmacological agents to Katp channels and iPLA2 and synthetic peptide inhibitors of PKCepsilon, we go on to demonstrate that these three gene products are involved in the urocortin induced protection of cardiac myocyte mitochondria. These proteins may interact at the mitochondria to produce the protective effect. 相似文献
4.
Kurusu S Matsui K Watanabe T Tsunou T Kawaminami M 《Cellular and molecular neurobiology》2008,28(8):1109-1118
This study characterized the phospholipase A2 (PLA2) activity in cerebral cortex of fetal rat brain and investigated effects of chemical inhibition of Ca2+-independent PLA2 (iPLA2) on neurite outgrowth and cell development of cortical neurons in vitro. The PLA2 activity in fetal brain was insensitive to a Ca2+-chelator EGTA and was significantly impaired by an iPLA2 inhibitor, bromoenol lactone (BEL). Following treatment with BEL, cortical neurons showed acute loss of neurites and impaired
cell body, which were clearly dose- and time-dependent. Nuclear staining revealed nuclear regression (shrinkage), but not
fragmentation, in BEL-treated cells. The cytotoxic effect of BEL was additive with arachidonic acid (AA) and AA alone also
induced neurite demise. BEL treatment resulted in increased production of prostaglandin E2. Overall data suggest that iPLA2, a primary PLA2 isoform in cerebral cortex, displays a housekeeping role in development and neurite outgrowth in cortical neurons in vitro
probably via maintaining phospholipid membrane remodeling rather than generating free fatty acids and lysophospholipids. 相似文献
5.
Angelo O. Rosa Stanley I. Rapoport 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(8):697-705
Docosahexaenoic acid (DHA) and arachidonic acid (AA) are found in high concentrations in brain cell membranes and are important for brain function and structure. Studies suggest that AA and DHA are hydrolyzed selectively from the sn-2 position of synaptic membrane phospholipids by Ca2+-dependent cytosolic phospholipase A2 (cPLA2) and Ca2+-independent phospholipase A2 (iPLA2), respectively, resulting in increased levels of the unesterified fatty acids and lysophospholipids. Cell studies also suggest that AA and DHA release depend on increased concentrations of Ca2+, even though iPLA2 has been thought to be Ca2+-independent. The source of Ca2+ for activation of cPLA2 is largely extracellular, whereas Ca2+ released from the endoplasmic reticulum can activate iPLA2 by a number of mechanisms. This review focuses on the role of Ca2+ in modulating cPLA2 and iPLA2 activities in different conditions. Furthermore, a model is suggested in which neurotransmitters regulate the activity of these enzymes and thus the balanced and localized release of AA and DHA from phospholipid in the brain, depending on the primary source of the Ca2+ signal. 相似文献
6.
Mireille Basselin Angelo O. Rosa Epolia Ramadan Yewon Cheon Lisa Chang Mei Chen Deanna Greenstein Mary Wohltmann John Turk Stanley I. Rapoport 《Journal of lipid research》2010,51(11):3166-3173
Ca2+-independent phospholipase A2β (iPLA2β) selectively hydrolyzes docosahexaenoic acid (DHA, 22:6n-3) in vitro from phospholipid. Mutations in the PLA2G6 gene encoding this enzyme occur in patients with idiopathic neurodegeneration plus brain iron accumulation and dystonia-parkinsonism without iron accumulation, whereas mice lacking PLA2G6 show neurological dysfunction and neuropathology after 13 months. We hypothesized that brain DHA metabolism and signaling would be reduced in 4-month-old iPLA2β-deficient mice without overt neuropathology. Saline or the cholinergic muscarinic M1,3,5 receptor agonist arecoline (30 mg/kg) was administered to unanesthetized iPLA2β−/−, iPLA2β+/−, and iPLA2β+/+ mice, and [1-14C]DHA was infused intravenously. DHA incorporation coefficients k* and rates Jin, representing DHA metabolism, were determined using quantitative autoradiography in 81 brain regions. iPLA2β−/− or iPLA2β+/− compared with iPLA2β+/+ mice showed widespread and significant baseline reductions in k* and Jin for DHA. Arecoline increased both parameters in brain regions of iPLA2β+/+ mice but quantitatively less so in iPLA2β−/− and iPLA2β+/− mice. Consistent with iPLA2β’s reported ability to selectively hydrolyze DHA from phospholipid in vitro, iPLA2β deficiency reduces brain DHA metabolism and signaling in vivo at baseline and following M1,3,5 receptor activation. Positron emission tomography might be used to image disturbed brain DHA metabolism in patients with PLA2G6 mutations. 相似文献
7.
Yewon Cheon Hyung-Wook Kim Miki Igarashi Hiren R. Modi Lisa Chang Kaizong Ma Deanna Greenstein Mary Wohltmann John Turk Stanley I. Rapoport Ameer Y. Taha 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2012,1821(9):1278-1286
Calcium-independent phospholipase A2 group VIA (iPLA2β) releases docosahexaenoic acid (DHA) from phospholipids in vitro. Mutations in the iPLA2β gene, PLA2G6, are associated with dystonia-parkinsonism and infantile neuroaxonal dystrophy. To understand the role of iPLA2β in brain, we applied our in vivo kinetic method using radiolabeled DHA in 4 to 5-month-old wild type (iPLA2β+/+) and knockout (iPLA2β−/−) mice, and measured brain DHA kinetics, lipid concentrations, and expression of PLA2, cyclooxygenase (COX), and lipoxygenase (LOX) enzymes. Compared to iPLA2β+/+ mice, iPLA2β−/− mice showed decreased rates of incorporation of unesterified DHA from plasma into brain phospholipids, reduced concentrations of several fatty acids (including DHA) esterified in ethanolamine- and serine-glycerophospholipids, and increased lysophospholipid fatty acid concentrations. DHA turnover in brain phospholipids did not differ between genotypes. In iPLA2β−/− mice, brain levels of iPLA2β mRNA, protein, and activity were decreased, as was the iPLA2γ (Group VIB PLA2) mRNA level, while levels of secretory sPLA2-V mRNA, protein, and activity and cytosolic cPLA2-IVA mRNA were increased. Levels of COX-1 protein were decreased in brain, while COX-2 protein and mRNA were increased. Levels of 5-, 12-, and 15-LOX proteins did not differ significantly between genotypes. Thus, a genetic iPLA2β deficiency in mice is associated with reduced DHA metabolism, profound changes in lipid-metabolizing enzyme expression (demonstrating lack of redundancy) and of phospholipid fatty acid content of brain (particularly of DHA), which may be relevant to neurologic abnormalities in humans with PLA2G6 mutations. 相似文献
8.
Jeong EM Ahn KH Jeon HJ Kim HD Lee HS Jung SY Jung KM Kim SK Bonventre JV Kim DK 《Molecules and cells》2011,32(5):405-413
The Ca2+-independent phospholipase A2 (iPLA2) subfamily of enzymes is associated with arachidonic acid (AA) release and the subsequent increase in fatty acid turnover.
This phenomenon occurs not only during apoptosis but also during inflammation and lymphocyte proliferation. In this study,
we purified and characterized a novel type of iPLA2 from bovine brain. iPLA2 was purified 4,174-fold from the bovine brain by a sequential process involving DEAE-cellulose anion exchange, phenyl-5PW
hydrophobic interaction, heparin-Sepharose affinity, Sephacryl S-300 gel filtration, Mono S cation exchange, Mono Q anion
exchange, and Superose 12 gel filtration. A single peak of iPLA2 activity was eluted at an apparent molecular mass of 155 kDa during the final Superose 12 gel-filtration step. The purified
enzyme had an isoelectric point of 5.3 on twodimensional gel electrophoresis (2-DE) and was inhibited by arachidonyl trifluoromethyl
ketone (AACOCF3), Triton X-100, iron, and Ca2+. However, it was not inhibited by bromoenol lactone (BEL), an inhibitor of iPLA2, and adenosine triphosphate (ATP). The spot with the iPLA2 activity did not match with any known protein sequence, as determined by matrix-assisted laser desorption/ionization time-of-flight
(MALDI-TOF) analysis. Altogether, these data suggest that the purified enzyme is a novel form of cytosolic iPLA2. 相似文献
9.
Epolia Ramadan Angelo O. Rosa Lisa Chang Mei Chen Stanley I. Rapoport Mireille Basselin 《Journal of lipid research》2010,51(8):2334-2340
In vitro studies show that docosahexaenoic acid (DHA) can be released from membrane phospholipid by Ca2+-independent phospholipase A2 (iPLA2), Ca2+-independent plasmalogen PLA2 or secretory PLA2 (sPLA2), but not by Ca2+-dependent cytosolic PLA2 (cPLA2), which selectively releases arachidonic acid (AA). Since glutamatergic NMDA (N-methyl-D-aspartate) receptor activation allows extracellular Ca2+ into cells, we hypothesized that brain DHA signaling would not be altered in rats given NMDA, to the extent that in vivo signaling was mediated by Ca2+-independent mechanisms. Isotonic saline, a subconvulsive dose of NMDA (25 mg/kg), MK-801, or MK-801 followed by NMDA was administered i.p. to unanesthetized rats. Radiolabeled DHA or AA was infused intravenously and their brain incorporation coefficients k*, measures of signaling, were imaged with quantitative autoradiography. NMDA or MK-801 compared with saline did not alter k* for DHA in any of 81 brain regions examined, whereas NMDA produced widespread and significant increments in k* for AA. In conclusion, in vivo brain DHA but not AA signaling via NMDA receptors is independent of extracellular Ca2+ and of cPLA2. DHA signaling may be mediated by iPLA2, plasmalogen PLA2, or other enzymes insensitive to low concentrations of Ca2+. Greater AA than DHA release during glutamate-induced excitotoxicity could cause brain cell damage. 相似文献
10.
A short period of ischemia followed by reperfusion (ischemic preconditioning) is known to trigger mechanisms that contribute to the prevention of ATP depletion. In ischemic conditions, most of the ATP hydrolysis can be attributed to mitochondrial F1F0-ATPase (ATP synthase). The purpose of the present study was to examine the effect of myocardial ischemic preconditioning on the kinetics of ATP hydrolysis by F1F0-ATPase. Preconditioning was accomplished by three 3-min periods of global ischemia separated by 3 min of reperfusion. Steady state ATP hydrolysis rates in both control and preconditioned mitochondria were not significantly different. This suggests that a large influence of the enzyme on the preconditioning mechanism may be excluded. However, the time required by the reaction to reach the steady state rate was increased in the preconditioned group before sustained ischemia, and it was even more enhanced in the first 5 min of reperfusion (101 ± 3.0 sec in preconditioned vs. 83.4 ± 4.4 sec in controls, p 0.05). These results suggest that this transient increase in activation time may contribute to the cardioprotection by slowing the ATP depletion in the very critical early phase of post-ischemic reperfusion. 相似文献
11.
Han MS Lim YM Quan W Kim JR Chung KW Kang M Kim S Park SY Han JS Park SY Cheon HG Dal Rhee S Park TS Lee MS 《Journal of lipid research》2011,52(6):1234-1246
The mechanism of FFA-induced insulin resistance is not fully understood. We have searched for effector molecules(s) in FFA-induced insulin resistance. Palmitic acid (PA) but not oleic acid (OA) induced insulin resistance in L6 myotubes through C-Jun N-terminal kinase (JNK) and insulin receptor substrate 1 (IRS-1) Ser307 phosphorylation. Inhibitors of ceramide synthesis did not block insulin resistance by PA. However, inhibition of the conversion of PA to lysophosphatidylcholine (LPC) by calcium-independent phospholipase A2 (iPLA2) inhibitors, such as bromoenol lactone (BEL) or palmitoyl trifluoromethyl ketone (PACOCF3), prevented insulin resistance by PA. iPLA2 inhibitors or iPLA2 small interfering RNA (siRNA) attenuated JNK or IRS-1 Ser307 phosphorylation by PA. PA treatment increased LPC content, which was reversed by iPLA2 inhibitors or iPLA2 siRNA. The intracellular DAG level was increased by iPLA2 inhibitors, despite ameliorated insulin resistance. Pertussis toxin (PTX), which inhibits LPC action through the G-protein coupled receptor (GPCR)/Gαi, reversed insulin resistance by PA. BEL administration ameliorated insulin resistance and diabetes in db/db mice. JNK and IRS-1Ser307 phosphorylation in the liver and muscle of db/db mice was attenuated by BEL. LPC content was increased in the liver and muscle of db/db mice, which was suppressed by BEL. These findings implicate LPC as an important lipid intermediate that links saturated fatty acids to insulin resistance. 相似文献
12.
Pasdois P Beauvoit B Tariosse L Vinassa B Bonoron-Adèle S Santos PD 《Journal of bioenergetics and biomembranes》2006,38(2):101-112
It has been proposed that activation of the mitochondrial ATP-sensitive potassium channel (mitoKATP) is part of signaling pathways triggering the cardioprotection afforded by ischemic preconditioning of the heart. This work was to analyze the mitochondrial function profile of Langendorff-perfused rat hearts during the different phases of various ischemia-reperfusion protocols. Specifically, skinned fibers of ischemic preconditioned hearts exhibit a decline in the succinate-supported respiration and complex II activity during ischemia, followed by a recovery during reperfusion. Meanwhile, the apparent affinity of respiration for ADP (which reflects the matrix volume expansion) is increased during preconditioning stimulus and, to a larger extent, during prolonged ischemia. This evolution pattern is mimicked by diazoxide and abolished by 5-hydroxydecanoate. It is concluded that opening the mitoKATP channel mediates the preservation of mitochondrial structure-function via a mitochondrial matrix shrinkage and a reversible inactivation of complex II during prolonged ischemic insult. 相似文献
13.
Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury 总被引:2,自引:0,他引:2
Hayashida K Sano M Ohsawa I Shinmura K Tamaki K Kimura K Endo J Katayama T Kawamura A Kohsaka S Makino S Ohta S Ogawa S Fukuda K 《Biochemical and biophysical research communications》2008,373(1):30-35
Inhalation of hydrogen (H2) gas has been demonstrated to limit the infarct volume of brain and liver by reducing ischemia-reperfusion injury in rodents. When translated into clinical practice, this therapy must be most frequently applied in the treatment of patients with acute myocardial infarction, since angioplastic recanalization of infarct-related occluded coronary artery is routinely performed. Therefore, we investigate whether H2 gas confers cardioprotection against ischemia-reperfusion injury in rats. In isolated perfused hearts, H2 gas enhances the recovery of left ventricular function following anoxia-reoxygenation. Inhaled H2 gas is rapidly transported and can reach ‘at risk’ ischemic myocardium before coronary blood flow of the occluded infarct-related artery is reestablished. Inhalation of H2 gas at incombustible levels during ischemia and reperfusion reduces infarct size without altering hemodynamic parameters, thereby preventing deleterious left ventricular remodeling. Thus, inhalation of H2 gas is promising strategy to alleviate ischemia-reperfusion injury coincident with recanalization of coronary artery. 相似文献
14.
Kim HW Rao JS Rapoport SI Igarashi M 《Prostaglandins, leukotrienes, and essential fatty acids》2011,85(6):361-368
Knowing threshold changes in brain lipids and lipid enzymes during dietary n-3 polyunsaturated fatty acid deprivation may elucidate dietary regulation of brain lipid metabolism. To determine thresholds, rats were fed for 15 weeks DHA-free diets having graded reductions of α-linolenic acid (α-LNA). Compared with control diet (4.6% α-LNA), plasma DHA fell significantly at 1.7% dietary α-LNA while brain DHA remained unchanged down to 0.8% α-LNA, when plasma and brain docosapentaenoic acid (DPAn-6) were increased and DHA-selective iPLA2 and COX-1 activities were downregulated. Brain AA was unchanged by deprivation, but AA selective-cPLA2, sPLA2 and COX-2 activities were increased at or below 0.8% dietary α-LNA, possibly in response to elevated brain DPAn-6. In summary, homeostatic mechanisms appear to maintain a control brain DHA concentration down to 0.8% dietary DHA despite reduced plasma DHA, when DPAn-6 replaces DHA. At extreme deprivation, decreased brain iPLA2 and COX-1 activities may reduce brain DHA loss. 相似文献
15.
François-Xavier Boittin George Shapovalov Urs T. Ruegg 《Biochemical and biophysical research communications》2010,391(1):401-406
Duchenne muscular dystrophy is an inherited disease caused by the absence of dystrophin, a structural protein normally located under the sarcolemma of skeletal muscle fibers. Muscle degeneration occurring in this disease is thought to be partly caused by increased Ca2+ entry through sarcolemmal cationic channels. Using the Mn2+ quench method, we show here that Mn2+ entry triggered by Ca2+ store depletion but not basal Mn2+ entry relies on Ca2+-independent PLA2 (iPLA2) activity in dystrophic fibers isolated from a murine model of Duchenne muscular dystrophy, the mdx5cv mouse. iPLA2 was found to be localized in the vicinity of the sarcolemma and consistently, the iPLA2 lipid product lysophosphatidylcholine was found to trigger Ca2+ entry through sarcolemmal channels, suggesting that it acts as an intracellular messenger responsible for store-operated channels opening in dystrophic fibers. Our results suggest that inhibition of iPLA2 and lysophospholipid production may be of interest to reduce Ca2+ entry and subsequent degeneration of dystrophic muscle. 相似文献
16.
The mechanisms of cell death induced by hypoxia or ischemia are not yet fully understood. We have previously demonstrated that cell death induced by hypoxia occurs independently of caspases, and is mediated by phospholipase A2 (PLA2).Here, we show that p38 mitogen-activated protein kinase is activated under hypoxia. A selective inhibitor of p38 or decrease in the p38alpha protein level prevents hypoxia-induced cell death. The p38 inhibitor abolishes PLA2 activation by hypoxia, indicating that p38 acts upstream of PLA2. The antioxidant N-acetyl-cysteine inhibits activation of p38 and cell death induced by hypoxia, indicating that reactive oxygen species (ROS) are responsible for p38 activation. These results demonstrate that the ROS/p38/PLA2 signaling axis has a crucial role in caspase-independent cell death induced by hypoxia. 相似文献
17.
Hongyan Zhang Wenxia WangHeng Yin Xiaoming Zhao Yuguang Du 《Carbohydrate polymers》2012,87(3):2270-2278
Oligochitosan has been proved to trigger plant cell death. To gain some insights into the mechanisms of oligochitosan-induced cell death, the nature of oligochitosan-induced cell death and the role of calcium (Ca2+), nitric oxide (NO) and hydrogen peroxide (H2O2) were studied in tobacco suspension cells. Oligochitosan-induced cell death occurred in cytoplasmic shrinkage, phosphatidylserine externalization, chromatin condensation, TUNEL-positive nuclei, cytochrome c release and induction of programmed cell death (PCD)-related gene hsr203J, suggesting the activation of PCD pathway. Pretreatment cells with cyclosporin A, resulted in reducing oligochitosan-induced cytochrome c release and cell death, indicating oligochitosan-induced PCD was mediated by cytochrome c. In the early stage, cells undergoing PCD showed an immediate burst in free cytosolic Ca2+ ([Ca2+]cyt) elevation, NO and H2O2 production. Further study showed that these three signals were involved in oligochitosan-induced PCD, while Ca2+ and NO played a negative role in this process by modulating cytochrome c release. 相似文献
18.
Activation of phospholipases A2 (PLA2s) leads to the generation of biologically active lipid mediators that can affect numerous cellular events. The Group VIA Ca2+-independent PLA2, designated iPLA2β, is active in the absence of Ca2+, activated by ATP, and inhibited by the bromoenol lactone suicide inhibitor (BEL). Over the past 10–15 years, studies using BEL have demonstrated that iPLA2β participates in various biological processes and the recent availability of mice in which iPLA2β expression levels have been genetically-modified are extending these findings. Work in our laboratory suggests that iPLA2β activates a unique signaling cascade that promotes β-cell apoptosis. This pathway involves iPLA2β dependent induction of neutral sphingomyelinase, production of ceramide, and activation of the intrinsic pathway of apoptosis. There is a growing body of literature supporting β-cell apoptosis as a major contributor to the loss of β-cell mass associated with the onset and progression of Type 1 and Type 2 diabetes mellitus. This underscores a need to gain a better understanding of the molecular mechanisms underlying β-cell apoptosis so that improved treatments can be developed to prevent or delay the onset and progression of diabetes mellitus. Herein, we offer a general review of Group VIA Ca2+-independent PLA2 (iPLA2β) followed by a more focused discussion of its participation in β-cell apoptosis. We suggest that iPLA2β-derived products trigger pathways which can lead to β-cell apoptosis during the development of diabetes. 相似文献
19.
Knight RA Chen-Scarabelli C Yuan Z McCauley RB Di Rezze J Scarabelli GM Townsend PA Latchman D Saravolatz L Faggian G Mazzucco A Chowdrey HS Stephanou A Scarabelli TM 《FEBS letters》2008,582(6):984-990
This study evaluates whether cardiac ischemia induces release of urocortin, before and independently from myocyte cell death. Urocortin levels rose after 5-min ischemia and peaked after 10-min ischemia, when cell death was not detected. However, myocyte apoptosis and/or necrosis occurred following 20- and 30-min ischemia, which paralleled a fall in urocortin levels, suggesting that urocortin expression and release are mainly sustained by metabolically challenged, though still viable myocytes. Hence, since cardiac release of urocortin, unlike that of conventional biomarkers, occurs before and apart from cell death, urocortin levels may be clinically useful in the diagnosis of sublethal myocardial ischemia. 相似文献
20.
J.D. Líbano-Soares 《生物化学与生物物理学报:生物膜》2008,1778(5):1316-1323
In a previous paper we showed that bradykinin (BK), interacting with its B2 receptor, inhibits proximal tubule Na+-ATPase activity but does not change (Na+ + K+)ATPase activity. The aim of this paper was to investigate the molecular mechanisms involved in B2-mediated modulation of proximal tubule Na+-ATPase by BK. To abolish B1 receptor-mediated effects, all experiments were carried out in the presence of (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Leu), des-Arg9-[Leu8]-BK (DALBK), a specific antagonist of B1 receptor. A dual effect on the Na+-ATPase activity through the B2 receptor was found: short incubation times (1-10 min) stimulate the enzyme activity; long incubation times (10-60 min) inhibit it. The stimulatory effect of BK is mediated by activation of phosphoinositide-specific phospholipase C β (PI-PLCβ)/protein kinase C (PKC); its inhibitory action is mediated by Ca2+-independent phospholipase A2 (iPLA2). Prior activation of the PI-PLCβ/PKC pathway is required to activate the iPLA2-mediated inhibitory phase. These results reveal a new mechanism by which BK can modulate renal sodium excretion: coupling between B2 receptor and activation of membrane-associated iPLA2. 相似文献