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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제23권 제1호
- 발행연도
- 2019.1
- 수록면
- 37 - 45 (9page)
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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 -hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-ketoacid 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 KATP channel openers.
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참고문헌 (22)
참고문헌 신청
Yellon DM / 2007 / Myocardial reperfusion injury / N Engl J Med 357:1121~1135
Silachev DN / 2014 / The mitochondrion as a key regulator of ischaemic tolerance and injury / Heart Lung Circ 23:897~904
Abete P / 2011 / Ischemic preconditioning in the younger and aged heart / Aging Dis 2:138~148
Kloner RA / 2006 / Preconditioning, postconditioning and their application to clinical cardiology / Cardiovasc Res 70:297~307
Fukao T / 2014 / Ketone body metabolism and its defects / J Inherit Metab Dis 37:541~551
Silachev DN / 2014 / The mitochondrion as a key regulator of ischaemic tolerance and injury / Heart Lung Circ 23:897~904
Abete P / 2011 / Ischemic preconditioning in the younger and aged heart / Aging Dis 2:138~148
Kloner RA / 2006 / Preconditioning, postconditioning and their application to clinical cardiology / Cardiovasc Res 70:297~307
Fukao T / 2014 / Ketone body metabolism and its defects / J Inherit Metab Dis 37:541~551
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