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Cardiovascular Research 2007 76(2):204-212; doi:10.1016/j.cardiores.2007.07.014
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Copyright © 2007, European Society of Cardiology

Role of mitochondria in angiotensin II-induced reactive oxygen species and mitogen-activated protein kinase activation

Guo-Xing Zhanga,*, Xiao-Mei Lua,b, Shoji Kimuraa and Akira Nishiyamaa

aDepartment of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
bDepartment of Pathophysiology, College of Basic Medical Science, China Medical University, ShenYang, 110001, China

*Corresponding author. Department of Pharmacology, Medical Faculty, Kagawa University, 1750-1 Miki-cho, Kagawa 761-0793, Japan. Tel.: +81 87 891 2125; fax: +81 87 891 2126. deep_red_maple{at}yahoo.com.cn

Peptide hormone Angiotensin II (Ang II) activates NAD(P)H oxidase, via AT1 receptors leading to increased generation of reactive oxygen species (ROS), such as the superoxide anion (O2). As an important intracellular second messenger, ROS can activate many downstream signaling molecules, including mitogen-activated protein kinases (MAPK), protein tyrosine phosphatases, protein tyrosine kinases, and transcriptional factors. Activation of these signaling cascades is highly related to risk for cardiovascular diseases. Accumulating evidence reveals that membrane-bound NAD(P)H oxidase is the main source responsible for Ang II-induced ROS generation. However, recent novel findings suggest that Ang II stimulation induces opening of mitochondrial KATP channels, depolarizes mitochondrial potential ({Delta}{psi}M), and further amplifies ROS generation from mitochondria, resulting in redox-sensitive activation of MAPK. In this review, we discuss the possible mechanisms of Ang II-induced cardiac pharmacological preconditioning (PC), and focus on the role of mitochondrial KATP channels, mitochondrial ROS production, and MAPK activation in response to Ang II stimulation.

KEYWORDS Angiotensin II (Ang II); Mitochondrial KATP channel; Mitogen-activated protein kinase (MAPK); Reactive oxygen species (ROS); Preconditioning (PC)


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