Redox regulation of angiotensin receptor signaling in the heart

Motohiro Nishida, Caroline Sunggip, Naoyuki Kitajima, Hitoshi Kurose

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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.

Original languageEnglish
Title of host publicationAngiotensin
Subtitle of host publicationNew Research
PublisherNova Science Publishers, Inc.
Pages165-180
Number of pages16
ISBN (Print)9781621007739
Publication statusPublished - Jan 1 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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