Roles of microRNA-1 in hypoxia-induced apoptotic insults to neuronal cells

Chia Yu Chang, Tai-Ngar Lui, Jia-Wei Lin, Yi Ling Lin, Chung-Hsi Hsing, Jhi Joung Wang, Ruei-Ming Chen

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Hypoxia is a common occurrence in brain tumors and traumatic brain injury. microRNA (miR)-1 participates in the regulation of brain development and neuronal function. Interestingly, miR-1 can mediate ischemia-induced injury to cardiomyocytes. This study was designed to evaluate the roles of miR-1 in hypoxia-induced insults to neurons and the possible mechanisms. Exposure of neuro-2a cells to oxygen/glucose deprivation (OGD) or cobalt chloride decreased cell viability and induced cell apoptosis in time-dependent manners. In parallel, OGD caused augmentation of cellular Bax and cytochrome c levels, a reduction in the mitochondrial membrane potential (MMP), activation of caspase-3, and fragmentation of DNA. miR-1 was induced in neuro-2a cells by OGD. Knocking down miR-1 expression using specific antisense inhibitors significantly alleviated OGD-induced neuronal death. Administration of OGD to neuro-2a cells induced heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search revealed that miR-1-specific binding elements exist in the 3′-untranslated region of HSP-70 mRNA. Overexpression of miR-1 simultaneously attenuated OGD-induced HSP-70 mRNA and protein expressions. In comparison, knocking down miR-1 expression synergistically enhanced OGD-induced HSP-70 mRNA. As to the mechanism, reducing miR-1 expression lowered OGD-induced alterations in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study shows that miR-1 can target HSP-70 expression and consequently mediate hypoxia-induced apoptotic insults to neuro-2a cells via an intrinsic Bax–mitochondrion–caspase protease pathway.

Original languageEnglish
Pages (from-to)191-202
JournalArchives of Toxicology
Volume90
Issue number1
DOIs
Publication statusAccepted/In press - Sep 20 2014

Keywords

  • HSP-70
  • Hypoxia
  • Intrinsic mechanism
  • miR-1
  • Neural apoptosis

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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