期刊
CARDIOVASCULAR RESEARCH
卷 77, 期 2, 页码 344-352出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvm050
关键词
mitochondrial K-ATP channel; mitochondrial permeability transition; protein kinase C; protein kinase G; reperfusion injury
资金
- NHLBI NIH HHS [HL36573, HL67842, HL50688, HL20468] Funding Source: Medline
Much of cell death from ischaemia/reperfusion in heart and other tissues is generally thought to arise from mitochondrial permeability transition (MPT) in the first minutes of reperfusion. In ischaemic pre-conditioning, agonist binding to G(i) protein-coupled receptors prior to ischaemia triggers a signalling cascade that protects the heart from MPT We believe that the cytosolic component of this trigger pathway terminates in activation of guanylyl cyclase resulting in increased production of cGMP and subsequent activation of protein kinase G (PKG). PKG phosphorylates a protein on the mitochondrial outer membrane (MOM), which then causes the mitochondrial K-ATP channel (mitoK(ATP)) on the mitochondrial inner membrane to open, leading to increased production of reactive oxygen species (ROS) by the mitochondria. This implies that the protective signal is somehow transmitted from the MOM to its inner membrane. This is accomplished by a series of intermembrane signalling steps that includes protein kinase C (PKC epsilon) activation. The resulting ROS then activate a second PKC pool which, through another signal transduction pathway termed the mediator pathway, causes inhibition of MPT and reduction in cell death.
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