Fatty acid amide hydrolase is a key regulator of endocannabinoid-induced myocardial tissue injury.
Fatty acid amide hydrolase is a key regulator of endocannabinoid-induced myocardial tissue injury.
复制标题
DOI：
10.1016/j.freeradbiomed.2010.11.002
复制
发表时间：
2011-01-01
影响因子：
7.4
通讯作者：
Pacher, Pal
中科院分区：
文献类型：
--
作者：
Mukhopadhyay, Partha;Horvath, Bela;Rajesh, Mohanraj;Matsumoto, Shingo;Saito, Keita;Batkai, Sandor;Patel, Vivek;Tanchian, Galin;Gao, Rachel Y.;Cravatt, Benjamin F.;Hasko, Gyoergy;Pacher, Pal
关键词：
Previous studies have suggested that increased levels of endocannabinoids in various cardiovascular disorders (e.g. different forms of shock, cardiomyopathies, atherosclerosis) through the activation of CB1 cannabinoid receptors may promote cardiovascular dysfunction and tissue injury. We have investigated the role of the main endocannabinoid anandamide metabolizing enzyme (fatty acid amide hydrolase; FAAH) in the myocardial injury induced by an important chemotherapeutic drug doxorubicin (DOX; known for its cardiotoxicity mediated by increased reactive oxygen and nitrogen species generation) using well-established acute and chronic cardiomyopathy models in mice. The DOX-induced myocardial oxidative/nitrative stress (increased 4-hydroxynonenal(HNE), protein carbonyl, nitrotyrosine levels, decreased glutathione content) correlated with multiple cell death markers, which were enhanced in FAAH knockout mice exhibiting significantly increased DOX-induced mortality and cardiac dysfunction compared to their wild types. The effects of DOX in FAAH knockouts were attenuated by CB1 receptor antagonists. Furthermore, anandamide induced enhanced cell death in human cardiomyocytes pretreated by FAAH inhibitor, and enhanced sensitivity to ROS generation in inflammatory cells of FAAH knockouts. These results suggest that in pathological conditions associated with acute oxidative/nitrative stress FAAH plays a key role in controlling the tissue injury, which is, at least in part, mediated by the activation of CB1 receptors by endocannabinoids.
登录
查看更多内容
内源性大麻素和心脏收缩功能：病理生理学影响。
影响因子：
9.3
作者：
Batkai, Sandor;Pacher, Pal
通讯作者：
Pacher, Pal
影响因子：
15.9
作者：
DOROSHOW, JH;LOCKER, GY;MYERS, CE
通讯作者：
MYERS, CE
影响因子：
3.4
作者：
Chandran, Karunakaran;Aggarwal, Deepika;Kalyanaraman, B.
通讯作者：
Kalyanaraman, B.
影响因子：
3.9
作者：
Konorev, EA;Kennedy, MC;Kalyanaraman, B
通讯作者：
Kalyanaraman, B
影响因子：
4.1
作者：
Kalivendi, SV;Konorev, EA;Kalyanaraman, B
通讯作者：
Kalyanaraman, B