Basic Research in Cardiology

, 112:60 | Cite as

MicroRNA-143 promotes cardiac ischemia-mediated mitochondrial impairment by the inhibition of protein kinase Cepsilon

  • Hong Hong
  • Ting Tao
  • Si Chen
  • Chaoqi Liang
  • Yue Qiu
  • Yuhong Zhou
  • Rong ZhangEmail author
Original Contribution


The cardioprotection of protein kinase Cepsilon (PKCε) against myocardial infarction (MI) mediated by its anti-apoptotic property and underlying mechanism of targeted regulation by microRNA (miRNA) are not established. MI-induced injury, PKCε expression, and targeted regulation of miRNA-143 (miR-143) to PKCε have been evaluated using animal MI and cellular hypoxic models conjugated with series of state-of-art molecular techniques. The results demonstrated that PKCε significantly downregulated along with increased infarcted area and apoptotic and necrotic damage in MI model, and the targeted relationship and potential binding profile were established between miR-143 and PKCε. Both in vivo and in vitro ischemic tests showed that miR-143 induced apoptosis and necrosis, which was reversed by antagomiR-143 or AMO-143. The upregulation of miR-143 by transfection of miR-143 in vitro also induced cell loss, and this effect of miR-143 was completely reversed by co-transfection of miR-143 with AMO-143. The identically deleterious action of miR-143 on mitochondrial membrane potential and ATP synthesis was also observed in both animal MI and cellular hypoxic models, as well as miR-143 overexpressed models and converted by either antagomiR or AMO. Importantly, overexpression of miR-143 downregulated PKCε in all tested models and this downregulation was reversed in the presence of antagomiR or AMO. The direct targeted regulation of miR-143 on PKCε was confirmed by luciferase reporter and miRNA-masking tests. In conclusion, MI-mediated upregulation of miR-143 inhibits PKCε expression and consequently interference with the cardioprotection of PKCε to mitochondrial, and leads to mitochondrial membrane potential dissipation and myocardial death eventually.


MicroRNA-143 Myocardial infarction PKCε Mitochondria Apoptosis Necrosis 



Protein kinase Cepsilon






Myocardial infarction


Transmission electron microscopy


Neonatal rat ventricular cardiomyocytes


Mitochondrial ATP-sensitive K(+) channel


Mitochondrial permeability transition pore


Mitochondrial membrane potential



Financial support was provided by the National Natural Science Foundation of China (81102434, 81470523, and 81673425).

Compliance with ethical standards

Conflict of interest

All the authors declare no competing financial interests.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of PharmacyHarbin Medical UniversityHarbinChina

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