Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

HIF-1α 的过度表达通过降低 miR-134 的表达保护 PC12 细胞免受 OGD/R 引起的损伤

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作者:Hongliang Zhang, Xianming Liu, Fengyu Yang, Dekui Cheng, Wei Liu

Abstract

Nowadays, searching for new therapeutic targets for cerebral stroke treatment are still in urgent need. Our study explored the influences and mechanisms of HIF-1α on OGD/R-evoked injury. OGD/R treatment was conducted on PC12 cells to simulate ischemic injury. CCK-8, flow cytometry and qRT-PCR were conducted to determine the variations of cell viability, apoptosis and gene expression, respectively. Cell transfections were conducted to overexpress HIF-1α and miR-134. Variations of protein levels were evaluated by employing western blot. Results showed that OGD/R treatment induced cell injury through reducing viability, while enhancing apoptosis that was validated by the elevated ratios of C/P-PARP and C/P-caspase-3. HIF-1α expression was markedly increased by OGD/R treatment. HIF-1α overexpression attenuated OGD/R-evoked injury in PC12 cells and remarkably reversed OGD/R-triggered inhibitory effects on ERK1/2 and JAK1/STAT3 pathways. Besides, miR-134 was also down-regulated by HIF-1α overexpression in PC12 cells. Up-regulation of miR-134 notably counteracted HIF-1α overexpression-triggered neuro-protective impacts on OGD/R-evoked injury and ERK1/2 and JAK1/STAT3 pathways. Our present study reported that HIF-1α overexpression protected PC12 cells against OGD/R-evoked injury via down-regulation of miR-134, which making HIF-1α and miR-134 to be promising targets for cerebral stroke therapy.

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