- 作者：Kazufumi Nakamura ; Daiji Miura ; Kengo Fukushima Kusano ; Yoshihisa Fujimoto ; Wakako Sumita-Yoshikawa ; Soichiro Fuke ; Nobuhiro Nishii ; Satoshi Nagase ; Yoshiki Hata ; Hiroshi Morita ; Hiromi Matsubara ; Tohru Ohe ; Hiroshi Ito
- 关键词：Reactive oxygen species ; heart failure ; calcium overload
- 刊名：Journal of Cardiac Failure
- 出版年：2009
- 出版时间：October 2009
- 年：2009
- 卷：15
- 期：8
- 页码：709-716
- 全文大小：761 K
BackgroundIt has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca2+ overload.Methods and Results
Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (·OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2′, 7′-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca2+ concentration ([Ca2+]i) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 μmol/L) exposure, hypercontracture was induced in 67 % of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H2O2), significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture. Carvedilol, a β-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca2+]i and completely inhibited hypercontracture, but propranolol had no effect on either [Ca2+]i increase or hypercontracture.
Conclusions
HNE induces the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.