Redox regulation of angiotensin receptor signaling in the heart

Motohiro Nishida, Caroline Sunggip, Naoyuki Kitajima, Hitoshi Kurose

研究成果: Chapter in Book/Report/Conference proceedingChapter

抄録

Cardiovascular diseases are leading cause of morbidity and mortality in developed countries. Renin-angiotensin system (RAS) and its effector molecule, angiotensin (Ang) II, play an important role in the pathophysiology of cardiovascular and kidney diseases. Most of the known pathophysiological effects of Ang II are mediated by Ang type 1 receptors (AT1Rs), and up-regulation of AT1Rs is an important event involves in undesired cardiovascular-renal crosstalk. Many lines of evidences have shown that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play significant roles in regulation of AT1R signaling. In our study, we reveal that AT1R-stimulated ROS production mediates activation of mitogen-activated protein kinases (MAPKs), leading to hypertrophic growth of cardiomyocytes and excessive cytokine production by cardiac fibroblasts. These findings indicate that ROS work as a crucial second messenger in Ang II-induced signaling. Endogenous ROS apparently increase AT1R expression level, while RNS down-regulates the expression of AT1R. The differences in the effects of ROS and RNS on AT1R expression can be explained by the local covalent modification of cysteine thiols that are found at active or allosteric sites of effector proteins. This review introduces the recent findings on molecular mechanisms underlying reduction/oxidation (redox)-dependent post-translational regulation of AT1R signaling in the cardiovascular system. These findings will provide a new understanding on the importance of cross talk between Ang II signaling and ROS/RNS in the development of heart failure.

本文言語英語
ホスト出版物のタイトルAngiotensin
ホスト出版物のサブタイトルNew Research
出版社Nova Science Publishers, Inc.
ページ165-180
ページ数16
ISBN(印刷版)9781621007739
出版ステータス出版済み - 1 1 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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