Attenuation of miR-34a protects cardiomyocytes against hypoxic stress through maintenance of glycolysis. Issue 6 (6th November 2017)

• Record Type: Journal Article
• Authors: Zhang, Ying; Liu, Gang; Gao, Xiaogang
• Is Part Of: Bioscience reports. Volume 37:Issue 6(2017)
• Publication Date: 2017-11-06
• Subjects: cardiomyocytes dysfunction -- glycolysis -- hypoxic stress -- LDHA -- miR-34a; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20170925
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : MiRNAs are a class of endogenous, short, single-stranded, non-coding RNAs, which are tightly linked to cardiac disorders such as myocardial ischemia/reperfusion (I/R) injury. MiR-34a is known to be involved in the hypoxia-induced cardiomyocytes apoptosis. However, the molecular mechanisms are unclear. In the present study, we demonstrate that under low glucose supply, rat cardiomyocytes are susceptible to hypoxia. Under short-time hypoxia, cellular glucose uptake and lactate product are induced but under long-time hypoxia, the cellular glucose metabolism is suppressed. Interestingly, an adaptive up-regulation of miR-34a by long-time hypoxia was observed both in vitro and in vivo, leading to suppression of glycolysis in cardiomyocytes. We identified lactate dehydrogenase-A (LDHA) as a direct target of miR-34a, which binds to the 3′-UTR region of LDHA mRNA in cardiomyocytes. Moreover, inhibition of miR-34a attenuated hypoxia-induced cardiomyocytes dysfunction through restoration of glycolysis. The present study illustrates roles of miR-34a in the hypoxia-induced cardiomyocytes dysfunction and proposes restoration of glycolysis of dysfunctional cardiomyocytes by inhibiting miR-34a during I/R might be an effectively therapeutic approach against I/R injury.