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)

The purpose of the present study was to determine whether the flavonoid, baicalin is effective at blunting the negative influence of ischemia/reperfusion to the rat retina in situ and of various insults to a transformed retinal ganglion cells (RGC-5 cells) in culture. Baicalin was administered intraperitoneally just before and after an ischemic insult to retina of one eye of a rat. Ischemia was delivered by raising the intraocular pressure above the systolic blood pressure for 50min. Seven days after ischemia, retinas were analysed for the localisation of various antigens. Retinal extracts were also analysed for various mRNAs. Moreover, the content of specific proteins was deduced in retinal and optic nerve extracts. Also, RGC-5 cells in culture were given one of three different insults, light (1000lx for 2 days), hydrogen peroxide (200microM H(2)O(2) for 24h) or serum deprivation (48h) where cell survival and reactive oxygen species (ROS) formation was assayed. Moreover, a lipid peroxidation assay was used to compare the antioxidant capacity of baicalin with the flavonoid, epigallocatechin gallate (EGCG). Ischemia/reperfusion to the retina affected the localisation of Thy-1 and choline acetyltransferase (ChAT) and the content of various proteins (optic nerve and retina) and mRNAs (retina). Importantly, baicalin statistically blunted most of the effects induced by ischemia/reperfusion. Only the increase in caspase-8 and caspase-3 mRNAs caused by ischemia/reperfusion were unaffected by baicalin treatment. Baicalin also attenuated significantly the negative insult of light, hydrogen peroxide and serum withdrawal to RGC-5 cells. In the lipid peroxidation studies, baicalin was also found to be equally effective as EGCG to act as an antioxidant. Significantly, the negative insult of serum withdrawal on RGC-5 cell survival was blunted by baicalin but not by EGCG revealing the different properties of the two flavonoids.
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PMID:The flavonoid baicalin counteracts ischemic and oxidative insults to retinal cells and lipid peroxidation to brain membranes. 1883 9

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

In view of the conventional wisdom in the cardiology literature that apoptosis is extensive early after myocardial ischemia, predicated largely from results with the TUNEL assay known to be nonspecific, this study was performed to delineate its extent with multiple assays and at multiple intervals. Coronary occlusion with and without subsequent revascularization was induced in 10-wk-old C57BL6 mice subjected to 1 or 4 h of transient ligation followed by 24 h of reperfusion, or 24 h persistent ligation. Apoptosis was quantified throughout the left ventricle immunohistochemically by assay of TUNEL, single-stranded DNA (ssDNA), and cleaved caspase 3; electron microscopy (EM); and activity assays of caspase 3 and 8. TUNEL staining was marked, but ssDNA and cleaved caspase 3 staining were significantly less (P<0.001 compared with TUNEL), and apoptosis defined by EM was virtually absent in all groups. Caspase 3 and caspase 8 activities per milligram protein were not significantly different from those in normal hearts. Only rare, potentially apoptotic cells were seen by EM in hearts from any group. Thus, the results with TUNEL were not specific, and the extent of apoptosis was markedly less than that predicated on the results with the TUNEL procedure. Apoptosis is de minimus early after transitory or persistent ischemia, though it is overestimated by TUNEL assays. Thus, antiapoptotic interventions per se are not likely to preserve substantial amounts of myocardium early after ischemic insults.
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PMID:The magnitude and temporal dependence of apoptosis early after myocardial ischemia with or without reperfusion. 1909 33

The purpose of the present study was to investigate the potential cardioprotective effects of an original approach based on the properties of the X chromosome-linked Inhibitor of Apoptosis (XIAP), the most effective endogenous inhibitor of apoptosis. For this purpose, the C-terminal part of XIAP (BIR3 and RING domains) was fused to the protein transduction domain (PTD) of the HIV1 transactivator of transcription, which confers to fused protein the ability to cross cell membranes. This protein, so-called PTD-BIR3/RING, was administered intravenously in C57BL/6J mice subjected to 30 min coronary artery occlusion and 24 h of reperfusion. Administration of PTD-BIR3/RING at 5 min before and 30 min after the onset of reperfusion reduced infarct size vs control (23+/-2% vs 41+/-4% and 27+/-4% vs 41+/-3%, respectively, p<0.05). Similar reduction in infarct size was observed when PTD-BIR3/RING was administered prior to ischemia (28+/-1% vs 44+/-3%). In addition to inhibition of caspase-3 and -9 activities, PTD-BIR3/RING induced an inhibition of caspase-8 and several other actors of the apoptotic pathways. In conclusion, this study demonstrates that the administration of PTD-BIR3/RING reduces myocardial infarct size even when injected during reperfusion through interruption of caspase activation by pharmacologically mimicking endogenous XIAP.
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PMID:Cardioprotection against myocardial infarction with PTD-BIR3/RING, a XIAP mimicking protein. 1923 93

The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors are widely expressed in the nervous system and various other tissues. PACAP exerts strong anti-apoptotic effects in neuronal cell lines and, according to recent data, also in non-neuronal cells. The peptide is present in the cardiovascular system and has various distinct effects. We have demonstrated earlier that PACAP has protective effects against in vitro ischemia/reperfusion-induced apoptosis in cardiomyocytes. Preconditioning with brief intermittent periods of ischemia is known to provide protection against ischemic injury. The aim of the present study was to investigate whether PACAP could enhance the protective effect of preconditioning against in vitro ischemic injury. Cultured cardiomyocytes were exposed to brief preconditioning ischemia followed by 2 h ischemia and 4 h reperfusion. Both PACAP treatment and preconditioning alone significantly increased cell viability and decreased the ratio of cell death. Pretreatment with PACAP was found to further reduce the level of cleaved caspase-8 but it did not lead to additional survival rate when compared to cells treated with PACAP or preconditioning alone. These results show that although both PACAP and preconditioning have a protective effect against ischemia/reperfusion-induced cardiomyocyte apoptosis, their effects are not additive.
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PMID:Effects of PACAP and preconditioning against ischemia/reperfusion-induced cardiomyocyte apoptosis in vitro. 1945 2

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

TNF-alpha has been reported to be relevant in stroke-induced neuronal death. However the precise function of TNF-alpha in brain ischemia remains controversial since there are data supporting either a detrimental or a protective effect. Here we show that TNF-alpha is released after oxygen-glucose deprivation (OGD) of cortical cultures and is a major contributor to the apoptotic death observed without affecting the OGD-mediated necrotic cell death. In this paradigm, apoptosis depends on TNF-alpha-induced activation of caspase-8 and -3 without affecting the activation of caspase-9. By using knock-out mice for TNF-alpha receptor 1, we show that the activation of both caspase-3 and -8 by TNF-alpha is mediated by TNF-alpha receptor 1. The pro-apoptotic role of TNF-alpha in OGD is restricted to neurons and microglia, since astrocytes do not express either TNF-alpha or TNF-alpha receptor 1. Altogether, these results show that apoptosis of cortical neurons after OGD is mediated by TNF-alpha/TNF-alpha receptor 1.
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PMID:Activation of caspase-8 by tumour necrosis factor receptor 1 is necessary for caspase-3 activation and apoptosis in oxygen-glucose deprived cultured cortical cells. 1955 59

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

Activation of phospholipase A(2), degradation of membrane phospholipids resulting in tissue accumulation of arachidonic acid, and the activation of cyclooxygenase that leads to the formation of prostaglandin and free radicals may occur after hypoxic-ischemic damage. The aim of this study was to investigate the effects of indomethacin, a nonselective cyclooxygenase inhibitor, on caspase activity, glutathione levels and lipid peroxidation in newborn rats with hypoxic-ischemic encephalopathy. The effects of indomethacin were evaluated by measuring caspase-3 and caspase-8 activities and glutathione levels. Lipid peroxidation was evaluated by measuring concentrations of malondialdehyde in rat brains. Seven-day-old rat pups with the Levine-Rice model of hypoxic-ischemic cerebral injury were randomly divided into three study groups. In the indomethacin-treated group, rats were administered three doses of indomethacin, at a dose of 2 mg/kg every 12 h. Sham and the hypoxic-ischemic group of rats were given physiologic saline. The sham group underwent all surgical procedures except for arterial ligation. After 72 hours, the rats were decapitated and brain tissues were evaluated. Caspase-3 and caspase-8 activities and glutathione and malondialdehyde levels were evaluated in all groups. There was an obvious decrease in caspase-3 and caspase-8 activities and depleted glutathione levels were reversed in the indomethacin-treated group compared to the hypoxic-ischemia group (p<0.001). As indomethacin was unable to prevent lipid peroxidation, malondialdehyde concentrations increased to ischemia-induced levels. In conclusion, indomethacin administration after hypoxic-ischemic encephalopathy injury has a neuroprotective effect since it inhibits caspase activity and reverses the depletion of glutathione. However, it also aggravates lipid peroxidation-induced ischemia.
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PMID:The effects of indomethacin on caspases, glutathione level and lipid peroxidation in the newborn rats with hypoxic-ischemic cerebral injury. 1961 46

Pressure ulcer is a complex and significant health problem. Although the factors including pressure, shear, and ischemia have been identified in the etiology of pressure ulcer, the cellular and molecular mechanisms that contribute to the development of pressure ulcer are unclear. This study tested the hypothesis that the early-onset molecular regulation of pressure ulcer involves apoptosis in muscle tissue. Adult Sprague-Dawley rats were subjected to an in vivo protocol to mimic pressure-induced deep tissue injury. Static pressure was applied to the tibialis region of the right limb of the rats for 6 h each day on two consecutive days. The compression force was continuously monitored by a three-axial force transducer equipped in the compression indentor. The contralateral uncompressed limb served as intra-animal control. Tissues underneath the compressed region were collected for histological analysis, terminal dUTP nick-end labeling (TUNEL), cell death ELISA, immunocytochemical staining, and real-time RT-PCR gene expression analysis. The compressed muscle tissue generally demonstrated degenerative characteristics. TUNEL/dystrophin labeling showed a significant increase in the apoptotic muscle-related nuclei, and cell death ELISA demonstrated a threefold elevation of apoptotic DNA fragmentation in the compressed muscle tissue relative to control. Positive immunoreactivities of cleaved caspase-3, Bax, and Bcl-2 were evident in compressed muscle. The mRNA contents of Bax, caspase-3, caspase-8, and caspase-9 were found to be higher in the compressed muscle tissue than control. These results demonstrated that apoptosis is activated in muscle tissue following prolonged moderate compression. The data are consistent with the hypothesis that muscle apoptosis is involved in the underlying mechanism of pressure-induced deep tissue injury.
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PMID:Muscle apoptosis is induced in pressure-induced deep tissue injury. 1964 27


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