1. The β subunit of soluble guanylyl cyclase GUCY1B3 exerts cardioprotective effects against ischemic injury via the PKCε/Akt pathway
- Author
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Xiaomin Wang, Liu Yang, Jiang Hu, Wei Du, Xianda Meng, Pengxia Dong, Jianping Liu, Yong Zhang, Ruiping Zhao, Kai Sun, Hongyu Li, Meng Li, and Wensi Yi
- Subjects
Male ,0301 basic medicine ,Programmed cell death ,GUCY1B3 ,Myocardial Infarction ,Myocardial Ischemia ,Protein Kinase C-epsilon ,Pharmacology ,Biochemistry ,Nitric oxide ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Soluble Guanylyl Cyclase ,0302 clinical medicine ,Animals ,Myocytes, Cardiac ,Molecular Biology ,Protein kinase B ,Cyclic guanosine monophosphate ,Cells, Cultured ,PI3K/AKT/mTOR pathway ,Cell Death ,Cell Biology ,Rats ,Up-Regulation ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,cardiovascular system ,Soluble guanylyl cyclase ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
The soluble form of guanylyl cyclase (sGC) is the main receptor for the signaling agent nitric oxide (NO), which regulates cardiomyocyte contractile function and attenuates cardiomyocyte hypertrophy. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), a regulator of vascular tone, and cardiac NO-sGC-cGMP signaling modulates cardiac stress responses, including ischemia and reperfusion (IR) injury. Here, we investigated the role of GUCY1B3 (the β subunit of sGC) in cardiomyocyte IR injury and myocardial infarction (MI) in vitro and in vivo. GUCY1B3 was upregulated in neonatal rat ventricular myocytes in response to IR injury, and GUCY1B3 overexpression restored IR-induced cell death and apoptosis. Treatment with specific inhibitors of PKCδ, PKCε, and Akt suggested that the protective effects of GUCY1B3 were mediated by PKCε/Akt signaling. In a mouse model of coronary artery ligation-induced MI, GUCY1B3 silencing aggravated MI-induced cardiac dysfunction and increased infarct size and exacerbated cardiomyocyte apoptosis in association with the inactivation of PKCε and Akt. Our results suggest that GUCY1B3 exerts cardioprotective effects through the modulation of the PKCε/Akt activity and identify a potential mechanism involved in NO-sGC-cGMP signaling in the heart.
- Published
- 2018