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)

Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after 2, 5 and 15 min of transient global ischemia in gerbil forebrain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Morphological studies were also performed at the dorsal hippocampal level of coronal sections from the identical brains until 7 days after the reperfusion. Following 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal dentate granule cells at 1 and 3 h of the reperfusion. No histological change was observed in brain cells. Following 5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The induction of HSP70 mRNA in hippocampal CA1 cells sustained until 2 days, while that of HSC70 mRNA declined gradually. Only CA1 cells were lost at 7 days of the reperfusion. Following 15 min of ischemia, the mRNAs were induced in more extensive brain regions including neocortex and thalamic nuclei. In hippocampal CA1 cells, inductions of HSP70 and HSC70 mRNAs diminished by 2 days corresponding with the neuronal damage. HSC70 mRNA induction was not so much as HSP70 mRNA induction especially in hippocampal CA1 and thalamic cells. Our results showed that HSP70 and HSC70 mRNAs were generally induced together after transient ischemia, but that the inductions were spatially and chronologically different after different periods of ischemia. The dissociation of the induction was also found in cells severely injured after 5 and 15 min of ischemia.
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PMID:Temporal profile of the induction of heat shock protein 70 and heat shock cognate protein 70 mRNAs after transient ischemia in gerbil brain. 843 64

A significant dissociation of HSP70 and HSC70 heat shock mRNAs after a 10-min transient forebrain ischemia in gerbil was found only in the hippocampal CA1 neurons which eventually die after the initial ischemic insult, while other hippocampal neurons such as the dentate granule and the CA3 cells which survive ischemia expressed both mRNAs cooperatively. The dissociation was observed as early as after 8 h of reperfusion, a period far shorter than 3-4 days, when the cell death becomes pathologically evident. Thus, the dissociation may serve as a set of early biochemical markers for ischemic neuronal cell death.
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PMID:Dissociation of HSP70 and HSC70 heat shock mRNA inductions as an early biochemical marker of ischemic neuronal death. 847 91

The effect of pentobarbital on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brains was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. In sham control brains, HSP70 mRNA was scarcely present, whereas HSC70 mRNA was present in most cell populations. After a 5-min occlusion of bilateral common carotid arteries, HSP70 and HSC70 mRNAs were induced together in several cells and were especially dense in hippocampal dentate granule cells at 3 h, but the strong hybridization of the mRNAs continued only in hippocampal CA1 cells by 2 days. At 7 days after the ischemia, CA1 neuronal cell death was apparent, and the HSP70 mRNA disappeared and HSC70 mRNA content returned to the sham level, except for in the CA1 cells. Pretreatment with pentobarbital (40 mg/kg, i.p.) greatly reduced or inhibited the induction of HSP70 and HSC70 mRNAs at both early (3-h) and late (2-day) phases after ischemia. The drug also prevented CA1 cell death at 7 days along with the maintenance of expression of HSC70 mRNA at the sham control level. Hypothermic effects of pentobarbital were noted at 30 and 60 min after the reperfusion, whereas at 2 h there was no statistical significance between the control and drug-treated groups. The great reduction of HSP70 and HSC70 mRNA induction at both early and late phases after ischemia suggests that pentobarbital reduces intra-and/or postischemic stress and may protect CA1 cells from ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of HSP70 and HSC70 heat shock mRNA induction by pentobarbital after transient global ischemia in gerbil brain. 851 71

Paraplegia is a serious complication that sometimes results from operation on the thoracic aorta. The mechanism of spinal cord injury has been thought to involve tissue ischemia, and spinal motor neurons are suggested to be vulnerable to ischemia. The exact mechanism, however, is not fully understood. To evaluate the mechanism of such vulnerability of motor neurons, we attempted to make a reproducible model for spinal cord ischemia and statistically analyzed cell damage. With this model, induction of heat shock protein 70 (HSP70) and heat shock cognate protein (HSC70) messenger ribonucleic acid molecules were investigated with Northern blot analysis for up to 7 days of reperfusion after 5 or 15 minutes of ischemia. Immunohistochemical studies of their proteins were also done. (heat shock proteins are a set of markers of neuronal injury after ischemia.) After 5 minutes of ischemia, there was no induction of HSP70 and HSC70 messenger ribonucleic acid molecules or their proteins, and all cells remained intact. In contrast, after 15 minutes of ischemia, HSP70 messenger ribonucleic acid was induced at 8 hours of reperfusion, and HSC70 messenger ribonucleic acid was expressed continuously at the control level. Immunoreactivity of HSP70 protein was slightly induced at 8 hours of reperfusion selectively in motor neurons, and about 70% of motor neuron cells showed selective cell death after 7 days of reperfusion. This study demonstrated induction of HSP70 messenger ribonucleic acid and its protein in motor neuron cells after transient ischemia in the spinal cord. This phenomenon was not accompanied by HSC70 induction.
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PMID:Selective motor neuron death and heat shock protein induction after spinal cord ischemia in rabbits. 901 85

Rats were subjected to transient cerebral ischemia by four-vessel occlusion of 30 min duration, followed by 2, 4, 8 or 24 h of recovery. Total RNA was isolated from the cerebral cortex and hippocampus, and reverse transcribed into cDNA. Hsp40 mRNA levels of samples were evaluated by quantitative PCR. Transient cerebral ischemia caused a marked increase in hsp40 mRNA levels to about 250% and 500% of control in the cortex and hippocampus respectively. Since hsp40 exerts a critical regulatory function in the HSC70/HSP70 ATPase cycle, an ischemia-induced rise of hsp40 mRNA levels could mark the onset of the recovery process after transient ischemia. On the other hand, the inhibitory action of hsp40 on P58 (a protein that activates protein synthesis by blocking the interferon-induced double-stranded RNA-activated protein kinase PKR) implies that the rise in hsp40 expression may equally well contribute to the post-ischemic suppression of protein synthesis.
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PMID:Effects of transient cerebral ischemia on hsp40 mRNA levels in rat brain. 958 51

Acute myocardial ischemia initiates a cascade of cellular events that lead to irreversible injury. We previously described the transient nature of heat-shock induced cardioprotection; treatment with a catalase inhibitor abolished the cytoprotective actions without affecting expression levels of HSP71. Repeated, transient ischemic episodes augment the ischemic tolerance of affected myocardium but the fundamental cytoprotective mechanism(s) for both "early" and "delayed" preconditioning remains unclear. Increased cellular induction of protooncogenes, heat shock genes, and downstream effector proteins might play critical roles in the cytoprotection afforded by delayed preconditioning. We measured c-fos, c-jun, c-myc, and hsp70 induction in preconditioned (2 x 5-min ischemia/10-min reperfusion) and control rabbit hearts that either underwent 30- or 120-min coronary occlusion and 60-min reperfusion, or did not undergo subsequent sustained ischemia; the latter hearts were allowed to recover for 0, 1, 3, 6, 24, 48, 72, or 96 hours. Both c-fos and c-jun in ischemic tissue were strongly induced by ischemia-reperfusion injury and preconditioning pretreatment. However, expression levels diminished significantly by 1-h reperfusion and remained depressed during the 96-h recovery period. Hsp70 (inducible) mRNA expression levels were highest primarily in ischemic myocardium after 6-h recovery post-preconditioning; Hsp70 levels in ischemic myocardium were slightly stronger after 48-h recovery but subsequently diminished to barely detectable levels by 96-h post-preconditioning. Induction of c-fos and c-jun preceded that of Hsp70. These findings support the concept that upregulation of immediate early genes and heat shock genes plays an important role in myocardial adaptation to acute ischemic stress.
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PMID:Cardiac adaptation to ischemia-reperfusion injury. 1041 23

Extracellular adenosine (Ado) accumulates during brain ischemia. To investigate the pathophysiological role of Ado on glial cells under ischemic conditions, we examined the effect of Ado on the survival of C6 glial cells exposed to chemical ischemia (CI). Treatment with Ado during exposure to CI showed a marked protective effect, that was mediated via intracellular transport and conversion of Ado to inosine (Ino). In contrast, Ado exacerbated CI-mediated cell death when it was added during the recovery time after exposure to CI. Ado cytotoxicity was largely mediated via intracellular transport, but conversion of Ado to Ino abolished its toxicity. Ado-induced cell death was characteristic of apoptosis, and Ado increased the expression of a pro-apoptotic product Bax but decreased that of an anti-apoptotic product Bcl-2. Ado also suppressed the induction of two stress proteins HSC70 and HSP27. Furthermore, Ado induced cytochrome c release and increased caspase-3-like activity. These results indicate the dual opposing effects of Ado on glial cell survival. Intracellular accumulation of Ado can be both cytoprotective and cytotoxic, depending on its metabolic pathway.
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PMID:Opposing effects of adenosine on the survival of glial cells exposed to chemical ischemia. 1107 Apr 97

To test the hypothesis that heat-shock proteins (HSPs) mediate delayed cardioprotection of prior kappa-opioid receptor (kappa-OR) stimulation, we first correlated cellular injury and viability with the expression of HSP70s in isolated rat ventricular myocytes subjected to prior kappa-OR stimulation with the selective agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U-50488H) and delayed lethal simulated ischemia (LSI). Cell injury and viability were indicated by lactate dehydrogenase release and trypan blue exclusion, respectively. The reduced injury and increased viability after pretreatment with U-50488H were concentration dependent and correlated directly with the expression of both stress-inducible (HSP70) and constitutive (HSC70) proteins. The effects mimic those with metabolic inhibition preconditioning (MIP). The cardioprotection against LSI by pretreatment with U-50488H and MIP was abolished and antagonized, respectively, via blockade of the kappa-OR by its selective antagonist, nor-binaltorphimine. We also found that blockade of the production of HSP70 but not HSC70 blocked the inhibitory effect of pretreatment with U-50488H on injury and viability. These observations provide evidence that stress-inducible HSP70 mediates delayed cardioprotection of prior kappa-OR stimulation.
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PMID:Inducible HSP70 mediates delayed cardioprotection via U-50488H pretreatment in rat ventricular myocytes. 1140 66

We examined the effects of 3 days of exercise in a cold environment on the expression of left ventricular (LV) heat shock proteins (HSPs) and contractile performance during in vivo ischemia-reperfusion (I/R). Sprague-Dawley rats were divided into the following three groups (n = 12/group): 1) control, 2) exercise (60 min/day) at 4 degrees C (E-Cold), and 3) exercise (60 min/day) at 25 degrees C (E-Warm). Left anterior descending coronary occlusion was maintained for 20 min, followed by 30 min of reperfusion. Compared with the control group, both the E-Cold and E-Warm groups maintained higher (P < 0.05) LV developed pressure, first derivative of pressure development over time (+dP/dt), and pressure relaxation over time (-dP/dt) throughout I/R. Relative levels of HSP90, HSP72, and HSP40 were higher (P < 0.05) in E-Warm animals compared with both control and E-Cold. HSP10, HSP60, and HSP73 did not differ between groups. Exercise increased manganese superoxide dismutase (MnSOD) activity in both E-Warm and E-Cold hearts (P < 0.05). Protection against I/R-induced lipid peroxidation in the LV paralleled the increase in MnSOD activity whereas lower levels of lipid peroxidation were observed in both E-Warm and E-Cold groups compared with control. We conclude that exercise-induced myocardial protection against a moderate duration I/R insult is not dependent on increases in myocardial HSPs. We postulate that exercise-associated cardioprotection may depend, in part, on increases in myocardial antioxidant defenses.
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PMID:Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins. 1151 6

An ischemia-induced gene was screened using a differential display technique in mouse transient forebrain ischemia. One of the ischemia-responsive clones was found to encode mouse hsp40. HSP40 has a critical regulatory function in the HSC70 ATPase activity. Expression of hsp40 mRNA was low in the nonischemic mouse hippocampus, but it was significantly upregulated 4 hr after ischemia by Northern blot analysis. In situ hybridization analysis revealed hsp40 mRNA induction in the neuron. HSP40 protein expression was also enhanced in the pyramidal and dentate granular neurons from 2 to 4 days after ischemia. The temporal expression and distribution profile of HSC70 protein was similar to that of HSP40, and both proteins were colocalized in ischemic hippocampal neurons. In the gerbil transient forebrain ischemia model, both HSP40 and HSC70 proteins were expressed strongly in ischemia-resistant CA3 neurons and dentate granule cells 1 day after 5 min ischemia, but were not expressed in vulnerable CA1 neurons. However, both proteins were in parallel expressed in the tolerance-acquired CA1 neurons. Based on the current observation that both HSP40 and HSC70 proteins were synergistically expressed in the ischemia-resistant and tolerance-acquired neurons, cochaperone HSP40 may play a significant role against postischemic neuronal response and lead to cell survival through interaction with simultaneously induced HSC70.
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PMID:Synergistic induction of HSP40 and HSC70 in the mouse hippocampal neurons after cerebral ischemia and ischemic tolerance in gerbil hippocampus. 1175 79


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