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

Micro-RNAs (miRs) have emerged as key gene regulators in many diseases, including stroke. We recently reported that miR-30a protects N2A cells against ischemic injury, in part through enhancing beclin 1-mediated autophagy. The present study explores further the involvement of miR-30a in ischemia-induced apoptosis and its possible mechanisms in primary cortical neurons and stroked mouse brain. We demonstrate that miR-30a level is significantly decreased in cortical neurons after 1-hr oxygen-glucose deprivation (OGD)/24-hr reoxygenation. Overexpression of miR-30a aggravated the OGD-induced neuronal cell death, whereas inhibition of miR-30a attenuated necrosis and apoptosis as determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-di-phenyl-2H-tetrazolium bromide, lactate dehydrogenase, TUNEL, and cleaved caspase-3. The amount of HSPA5 protein, which is predicted to be a putative target of miR-30a by TargetScan, could be reduced by pre-miR-30a, whereas it was increased by anti-miR-30a. Furthermore, the luciferase reporter assay confirmed that miR-30a directly binds to the predicted 3'-UTR target sites of the hspa5 gene. The cell injury regulated by miR-30a in OGD-treated cells could be aggravated by HSPA5 siRNA. We also observed an interaction of HSPA5 and caspase-12 by coimmunoprecipitation and speculate that HSPA5 might be involved in endoplasmic reticulum stress-induced apoptosis. In vivo, reduced miR-30a increased the HSPA5 level and attenuated ischemic brain infarction in focal ischemia-stroked mice. Downregulation of miR-30a could prevent neural ischemic injury through upregulating HSPA5 protein expression, and decreased ER stress-induced apoptosis might be one of the mechanisms underlying HSPA5-mediated neuroprotection.
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PMID:Micro-RNA-30a regulates ischemia-induced cell death by targeting heat shock protein HSPA5 in primary cultured cortical neurons and mouse brain after stroke. 2630 16