Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Binding of oleate to S-nitrosylated human serum albumin (SNO-HSA) enhances its cytoprotective effect on liver cells in a rat ischemia/reperfusion model. It enhances the antiapoptotic effect of SNO-HSA on HepG2 cells exposed to anti-Fas antibody. To identify some of the reasons for the increased cytoprotective effects, additional experiments were performed with glutathione and HepG2 cells. As indicated by 5,5'-dithiobis-2-nitrobenzoic acid binding, the addition of oleate increased the accessibility of the single thiol group of albumin. Binding of increasing amounts of oleate resulted in increasing and more rapid S-transnitrosation of glutathione. Likewise, binding of oleate, or of a mixture of endogenous fatty acids, improved S-denitrosation of SNO-HSA by HepG2 cells. Oleate also enhanced S-transnitrosation by HepG2 cells, as detected by intracellular fluorescence of diaminofluorescein-FM. All of the S-transnitrosation caused by oleate binding was blocked by filipin III. Oleate also increased, in a dose-dependent manner, the binding of SNO-HSA labeled with fluorescein isothiocyanate to the surface of the hepatocytes. A model in two parts was worked out for S-transnitrosation, which does not involve low molecular weight thiols. Fatty acid binding facilitates S-denitrosation of SNO-HSA, increases its binding to HepG2 cells and greatly increases S-transnitrosation by hepatocytes in a way that is sensitive to filipin III. A small nitric oxide transfer takes place in a slow system, which is unaffected by fatty acid binding to SNO-HSA and not influenced by filipin III. Thus, fatty acids could be a novel type of mediator for S-transnitrosation.
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PMID:S-nitrosylated human serum albumin-mediated cytoprotective activity is enhanced by fatty acid binding. 1894 Aug 10

Estrogen is protective in experimental cerebral ischemia, yet the mechanism remains unclear. Fas-mediated apoptosis has been shown to be induced after cerebral ischemia and significantly contribute to ischemic brain damage. In this study, we tested if estrogen is protective against cerebral ischemia by suppressing Fas-mediated apoptosis. 17Beta-estradiol-treated and untreated ovariectomized (OVX) female mice were subjected to 2 h middle cerebral artery occlusion (MCAO). Expression of Fas and Fas-associated death domain (FADD) were measured at 3, 6 and 12 h of reperfusion by RT-PCR and Western blot, respectively. Post-ischemic activities of caspase-8 and -3 activities, the two downstream effectors of Fas-induced apoptosis, were also assayed at same time points by ELISA. Finally, Fas antibody-induced cell death in primary cortical neurons was assayed by fluorescence activated cell sorter (FACS) in the presence and absence of estradiol. Our data showed that estradiol-treated OVX female mice sustained smaller infarct compared to untreated OVX mice. Ischemia upregulated Fas and FADD expression, and increased caspase-8 and -3 activities in OVX female mouse cortex, which were significantly attenuated by estradiol. Estradiol also significantly inhibited Fas antibody-induced neuronal cell apoptosis. Our data suggests that inhibition of ischemia-induced Fas-mediated apoptosis is an important mechanism of neuroprotection by estrogen in cerebral ischemia.
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PMID:Estrogen inhibits Fas-mediated apoptosis in experimental stroke. 1895 Jun 22

The present study was designed to investigate the possible properties of the injured brain neurocytes, the expression of heat shock protein70 (HSP70) and Fas protein after acute local ischemia brain injury and local cerebral ischemia-reperfusion injury in rats and to investigate the protecting mechanism of puerarin on the brain neurocytes of rats in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury. A rat model of acute local cerebral ischemia was made by ligatting the middle cerebral artery. The rat model of local cerebral ischemia and reperfusion injury was made by ligatting the middle cerebral artery for 30 min then opened for 30 min. Rats of puerarin treating group were injected with puerarin in dose of 30 mg/kg(-1) by intraperitoneal injection 30 min before ischemia. HSP70 and Fas protein expressions in brain tissue were detected by SP method of histochemistry. In addition, dead brain neurocytes were counted and their morphology was observed. The results indicated that puerarin can limit the tissue injury caused by local cerebral ischemia injury through improving expression of HSP70, and limit the tissue injury caused by local cerebral ischemia-reperfusion through decreasing the Fas expression and improving expression of HSP70. On the basis of these results, it may be concluded that puerarin can protect the brain neurocytes of rats in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury, which may be different according to the different injury mechanism.
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PMID:Protecting mechanism of puerarin on the brain neurocyte of rat in acute local ischemia brain injury and local cerebral ischemia-reperfusion injury. 1898 5

We investigated the effects of the neuroprotective drug cerebrolysin on the autoimmune parameters (FasL, Fas and metallotionein-1) in 20 newborns with perinatal ischemic CNS damage and 20 healthy newborns. The treatment with cerebrolysin in dosage of 0,1 ml per 1 kg of body mass, 10 injections every other day, resulted in the normalization (p<0,001) of the T-lymphocyte apoptosis (the increase of Fas and decrease of FasL) and activation of antioxidant protection through the increase of metallotionein-1 expression. The normalization of the autoimmunity was found to reduce edema and improve the circulation of the brain sites affected with ischemia.
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PMID:[Cerebrolysin alleviates perinatal CNS disorders through the autoimmune modulation and antioxidant protection]. 1900 4

Hepatic ischemia reperfusion (HIR) not only results in liver injury, but also leads to endotoxemia, which aggravates HIR-induced liver injury and dysfunction, or even causes liver failure. Taurine has been shown to protect organs from ischemia reperfusion or endotoxin by its anti-oxidant and anti-inflammatory activities. The aim of this study was to investigate whether taurine could attenuate endotoxin-induced acute liver injury after HIR. Wistar rats subjected to 30 min of hepatic ischemia followed by reperfusion and lipopolysaccharide (LPS) (0.5 mg/kg) administration, exhibited liver dysfunction (elevated serum levels of ALT, AST and LDH) and hepatic histopathological alteration. The serum levels of TNF-alpha and production of myeloperoxidase (MPO) and malondialdehyde (MDA) in liver tissues and apoptosis of hepatocytes were also increased after the combination of HIR and LPS. However, pre-administration of taurine protected livers from injury induced by the combination of HIR + LPS as the histological score, apoptotic index, MPO activity and production of MDA in liver tissues, and serum levels of AST, ALT, LDH and TNF-alpha, were significantly reduced. The expression of caspase-3, Fas and Fas ligand was upregulated in homogenates of livers from rats subjected to HIR and LPS, and this elevated expression could be inhibited by taurine. In summary, the results further emphasize the potential utilization of taurine in protecting livers against endotoxin-induced injury especially after HIR, by its anti-inflammatory, anti-oxidative and anti-apoptotic activities.
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PMID:Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion. 1926 95

Previous work has demonstrated that ischemic preconditioning neuroprotection is associated with inhibition of JNK pathway activation. The present study was designed to examine the hypothesis that the suppression of JNK3 activation by preconditioning is mediated by NMDA receptors and crosstalk between ERK1/2 and JNK3. Preconditioning (3 min ischemia) 2 days before global cerebral ischemia (8-min) markedly decreased neuronal degeneration in hippocampus CA1, an effect abolished by pretreatment with the NMDA receptor antagonist, MK-801. Furthermore, preconditioning abolished cerebral ischemia-induced JNK3 activation and enhanced ERK1/2 activation, an effect reversed by MK-801. Due to the inverse relationship between ERK1/2 and JNK3 activation following preconditioning, we hypothesized that ERK1/2 may regulate JNK3 activation following preconditioning. In support of this contention, pretreatment with the MEK inhibitor, PD98059 significantly attenuated preconditioning-induced ERK1/2 phosphorylation, and strongly reversed preconditioning down-regulation of JNK3 phosphorylation. This finding suggests that ERK1/2 signaling is responsible for preconditioning-induced down-regulation of JNK3 activation. Western blot analysis and immunohistochemistry further demonstrated that preconditioning, in an NMDA-dependent manner, enhanced activation of the pro-survival factors, p-CREB and Bcl-2, while attenuating activation of putative pro-death factors, p-c-Jun and Fas-L in the hippocampus CA1. As a whole, the study demonstrates that preconditioning attenuation of pro-death JNK3 in the hippocampus CA1 following global cerebral ischemia is mediated by NMDA receptor-induced crosstalk between ERK1/2 and JNK3. The ERK1/2-mediated reduction of JNK3 activation leads to enhanced pro-survival signaling (P-CREB and Bcl-2 induction) and attenuation of pro-death signaling (p-c-Jun and Fas-L), with subsequent induction of ischemic tolerance.
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PMID:Preconditioning neuroprotection in global cerebral ischemia involves NMDA receptor-mediated ERK-JNK3 crosstalk. 1937 93

The aim of this study was to investigate the therapeutic efficacy and neuroprotective mechanisms of UCF-101, a novel Omi/HtrA2 inhibitor, following ischemia/reperfusion brain injury. Male Wistar rats were subjected to 2 hr of middle cerebral artery occlusion followed by reperfusion. Animals were divided into 3 groups: sham, vehicle-treated ischemia/reperfusion, and UCF-101 treatment. In the UCF-101 treatment group, rats were intraperitoneally administered UCF-101 (1.5 micromol/kg) 10 min prior to reperfusion. The rats were evaluated for neurological deficits, and brain infarct volume was assessed by 2,3,5-triphenyl tetrazolium chloride. TUNEL staining was utilized to evaluate the amount of apoptosis. In addition, expressions of protein caspase-8, caspase-3, FasL, and FLIP were examined by Western blot analysis. Results demonstrated that UCF-101 treatment significantly decreased cerebral infarct size by about 16.27% (P < 0.05) and also improved neurological behavior. TUNEL staining revealed that UCF-101 treatment significantly reduced TUNEL-positive cells in the cerebral cortex. Furthermore, the upregulation in the expression of FasL and the cleavage products of active caspase-8 and caspase-3 induced by ischemia was attenuated in mice treated with UCF-101, whereas upregulation of FLIP levels was increased. The present results demonstrated that UCF-101 protects against cerebral ischemia/reperfusion injury in mice. UCF-101 provided neuroprotection in vivo, and this was correlated with regulation of Fas-mediated apoptotic proteins. Taken together, the use of UCF-101 is a potent, neuroprotective factor for the treatment of focal cerebral ischemia.
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PMID:UCF-101, a novel Omi/HtrA2 inhibitor, protects against cerebral ischemia/reperfusion injury in rats. 1946 55

Hypothermia is the most effective means of protecting the brain, heart and other organs during ischemia/reperfusion (I/R) injury. However, the precise mechanisms for hypothermia to inhibit I/R-induced endothelial cell apoptosis are not fully understood. In the present study, human umbilical endothelial cells (HUVECs) were exposed to ischemia followed by reperfusion under normothermia (37 degrees C) or hypothermia (33 degrees C). Our results showed that hypothermia markedly reduced I/R-induced endothelial cell apoptosis, the expression of cleaved caspase-3 and PARP. Moreover, hypothermia markedly reversed I/R-induced activation of Fas/caspase-8, the increase of Bax and decrease of Bcl-2. Furthermore, hypothermia inhibited JNK1/2 activation via MKP-1 induction. Together, these data demonstrate that hypothermia represses I/R-induced endothelial cell apoptosis by inhibiting both extrinsic- and intrinsic-dependent apoptotic pathways and activation of JNK1/2.
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PMID:Hypothermia attenuates ischemia/reperfusion-induced endothelial cell apoptosis via alterations in apoptotic pathways and JNK signaling. 1959 1

Different postconditioning (Postcon) methods have been demonstrated to protect heart from ischemia/reperfusion injury. The relationship between Postcon by percutaneous coronary intervention (PCI) and apoptosis is not clear. Our objective was to test whether Postcon by PCI in patients with acute myocardial infarction (AMI) reduces myocardial apoptosis. Seventy-five patients were randomly assigned to one of three groups before stenting. The Routine group (n = 26) received no Postcon intervention prior to the onset of reperfusion; Postcon-30s (n = 25) and Postcon-60s groups (n = 24) underwent three cycles of 30- or 60-s balloon deflation and 30- or 60-s inflation. Additionally, 34 normal controls (NC) were enrolled in the study. Plasma concentrations of soluble Fas/APO-1 ([sFas]) and Fas ligand ([sFasL]) were determined at baseline and 7 days after PCI via ELISA. The [sFas] and [sFasL] in AMI patients were significantly elevated at baseline as compared with NC (P < 0.01), and showed an upward trend in the Routine group, a slightly upward trend in Postcon-30s, and a downward trend in Postcon-60s at 7 days. Comparison among the three groups showed significant differences (P < 0.05, 3.8 vs. 4.6 vs. 5.1 ng ml(-1)). The [sFasL] in Postcon-60s was significantly decreased at 7 days (P < 0.05, 3.9 vs. 3.1 ng ml(-1)) compared with baseline, but not Postcon-30s and Routine. More importantly, Postcon-60s group had the lowest [sFasL], followed by Postcon-30s, which had a lower value than Routine at 7 days (P < 0.05, 3.1 vs.3.7 vs. 4.2 ng ml(-1)). Our results suggest that Postcon-60s was visibly better than Postcon-30s, which in turn was better than Routine for inhibition of the effects of myocardial apoptosis and reduction of reperfusion injury in patients with acute myocardial infarction.
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PMID:A 60-s postconditioning protocol by percutaneous coronary intervention inhibits myocardial apoptosis in patients with acute myocardial infarction. 1969 75

Hydrogen sulfide (H2S) displays anti-inflammatory and cytoprotective activities as evidenced by the inhibition of myocardial ischemia-reperfusion injury and production of lipid peroxidation. H2S also exerts many physiological or pathological effects on livers. Therefore, we designed the present study to investigate the roles of H2S in hepatic ischemia-reperfusion (HIR)-induced injury in rats by measuring H2S levels, H2S synthesizing activity, and cystathionine gamma-lyase (CSE) messenger RNA (mRNA) expression. We also applied DL-propargyl glycine (PAG) and sodium hydrosulfide (NaHS) to investigate their effects on the severity of liver injury induced by HIR. The levels of H2S, H2S production activity, and CSE mRNA expression in livers were increased by HIR. Administration of NaHS significantly attenuated the severity of liver injury and inhibited the production of lipid peroxidation, serum inflammatory factors [including nitric oxide, tumor necrosis factor alpha (TNF-alpha), interleukin 10, and intercellular cell adhesion molecule 1], cell apoptosis, and apoptosis-related proteins (including caspase-3, Fas, Fas ligand, and TNF-alpha), which were caused or elevated by HIR, whereas PAG aggravated them. However, NaHS or PAG did not show significant effects on the activation of caspase-9, which was also increased by HIR. Although further investigation is required, this study may indicate that H2S plays a protective role in HIR-induced injury.
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PMID:Role of hydrogen sulfide in hepatic ischemia-reperfusion-induced injury in rats. 1979 Jan 58


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