期刊
CURRENT DRUG TARGETS
卷 11, 期 8, 页码 1032-1040出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138945010791591331
关键词
Cardiomyocyte; hypertrophy; apoptosis; mini-gene inhibitor; C-terminal peptide; proline-rich domains; phospholipase C; Gq
资金
- Australian National Health and Medical Research Council [418935, 317801, 317802, 317803]
- Australian National Heart Foundation [G09M3965]
- Baker IDI Heart and Diabetes Institute
Heart failure, the common end-point of many cardiac diseases, is a major contributor to mortality and morbidity and contributes considerably to health care costs. Current treatment regimens include beta-adrenergic antagonists, angiotensin converting enzyme inhibitors, and inotropic agents are used by some patients. Studies in experimental animals have demonstrated that inhibition of signaling pathways downstream of the heterotrimeric G protein Gq reduces ventricular hypertrophy and protects from the development of heart failure. However, targets identified, to date, have been limited by a lack of tissue specificity. In cardiomyocytes, Gq activates only one splice variant of one subtype of phospholipase C beta, specifically phospholipase C beta 1b (PLC beta 1b) and PLC beta 1b is responsible for Gq mediated hypertrophic and apoptotic responses. PLC beta 1b targets the sarcolemma via its unique C-terminal sequence and its activation can be inhibited by expressing the C-terminal sequence to compete for sarcolemmal binding. Inhibition of PLC beta 1b by the C-terminal peptide reduces hypertrophic responses in cardiomyocytes. We present the evidence that inhibition of the sarcolemmal association of PLC beta 1b provides a cardiac-specific target for the development of drugs to reduce pathological cardiac hypertrophy and thereby to reduce the burden of heart failure.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据