Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic/reperfusion brain injury (IRI) is a very severe event with the multiple etiopathogenesis. Ischemic preconditioning (IPC) is an important phenomenon of adaptation of CNS to subsequent ischemia. An altered cross-talk between intracellular calcium stores is presumed in the mechanisms of ischemic damage/protection. We show here that IRI leads to the inhibition of mitochondrial respiratory complexes I and IV, however due to the excess of their capacities, the mitochondrial Ca(2+) uptake rate is not significantly depressed. IPC acts at the level of both initiation and execution of IRI-induced mitochondrial apoptosis and protects from IRI-associated changes in integrity of mitochondrial membranes. IPC also activates inhibition of p53 translocation to mitochondria. Inhibition of the mitochondrial p53 pathway might thus provide a potentially important mechanism of neuronal survival after ischemic brain damage. In addition, IRI initiates a time dependent differences in endoplasmic reticular (ER) gene expression of the key UPR proteins at both the mRNA and protein levels. Moreover, gene expression of the UPR proteins is affected by preischemic treatment by the increased expression of Ca(2+) binding protein: GRP 78 and transcriptional factor ATF6 in reperfusion times. Thus, IPC exerts a role in the attenuation of ER stress response, which might be involved in the neuroprotective phenomenon of ischemic tolerance. Hippocampal cells respond to the IRI by the specific expression pattern of the secretory pathways Ca(2+) pump (SPCA1) and this pattern is affected by preischemic challenge. IPC also incompletely suppresses lipo- and protein oxidation of hippocampal membranes and leads to partial recovery of the ischemic-induced depression of SPCA activity. The data suggests the correlation of SPCA function with the role of secretory pathways (Golgi apparatus) in response to preischemic challenge. Documented functional alterations of mitochondria, ER and Golgi apparatus put light into the understanding of cross-talk between intracellular Ca(2+) stores in cerebral ischemia and ischemic tolerance and might suggest for possible targets of future therapeutic interventions to enhance recovery after stroke.
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PMID:Cross-talk of intracellular calcium stores in the response to neuronal ischemia and ischemic tolerance. 2009 20

The present study was designed to investigate the potential role of secretory pathway Ca(2+)-ATPase isoform 1(SPCA1) in experimental focal cerebral ischemia-reperfusion injury. Cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 2h s in Sprague-Dawley rats, and then the expression levels of SPAC1 mRNA and protein were determined. Results showed that SPCA1 level was transiently increased 1 day after reperfusion in peri-infarction area, while markedly increased in infarction core on 3day and 7 day after reperfusion. Then a SPCA1 lentivirus was used to achieve knockdown of SPCA1 gene: Ca(2+) transporting type 2C, member 1 (ATP2C1) gene. It has been observed that SPCA1 knockdown by lentivirus markedly increased cerebral infarction volume in vivo. Meanwhile, SPCA1 knockdown also facilitated per-oxidative production, including nitric oxide (NO) and 3-nitrotyrosine (3-NT) and decreased the expression of total superoxide dismutase (SOD) and manganese superoxide dismutase (MnSOD). Moreover, in vitro study showed that SPCA1 knockdown increased hydrogen peroxide (H2O2)-induced lactate dehydrogenase (LDH) leakage dose-dependently, and elevated caspase3 level in neuro-2a (N2a) cells. In addition, SPCA1 knockdown increased H2O2-induced production of nitric oxide and 3-NT dose-dependently, and reversed the increased activity of total SOD and MnSOD in neuro-2a cells. In conclusion, the present study indicated that SPCA1 could suppress over active Golgi apparatus (GA) stress thus attenuate cerebral ischemia-reperfusion injury.
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PMID:Secretory pathway Ca(2+)-ATPase isoform 1 knockdown promotes Golgi apparatus stress injury in a mouse model of focal cerebral ischemia-reperfusion: In vivo and in vitro study. 2873 34