Nicorandil alleviated cardiac hypoxia/reoxygenation-induced cytotoxicity via upregulating ketone body metabolism and ACAT1 activity.
10.4196/kjpp.2019.23.1.37
- Author:
Yan Ping BAI
1
;
Lei Sen HAN
Author Information
1. Department of Cardiology, The Affiliated Hospital of Yan'an University, Yan'an 716000, China.
- Publication Type:Original Article
- Keywords:
Acetyl-CoA acetyltransferase;
Hypoxia reoxygenation;
Ketone body;
Nicorandil;
OXCT1
- MeSH:
Acetyl-CoA C-Acetyltransferase;
Apoptosis;
Calcium;
Cell Line;
Coenzyme A;
Gene Expression;
Metabolism*;
Myocytes, Cardiac;
Nicorandil*;
Reactive Oxygen Species;
Transferases
- From:The Korean Journal of Physiology and Pharmacology
2019;23(1):37-45
- CountryRepublic of Korea
- Language:English
-
Abstract:
To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly β-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-keto-acid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other K(ATP) channel openers.
