The Pivotal Role of Cholesterol and Membrane Lipid Rafts in the Ca2+- Sensitization of Vascular Smooth Muscle Contraction Leading to Vasospasm

Ying Zhang, Hiroko Kishi, Katsuko Kajiya, Tomoka Morita, and Sei Kobayashi

Department of Molecular and Cellular Physiology Yamaguchi University, Graduate School of Medicine,

1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan

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The Rho-kinase (ROK)-mediated Ca2+-sensitization of vascular smooth muscles (VSM) contraction contributes to vasospasm, a major cause of acute-onset sudden death induced by vascular diseases such as ischemic heart and brain diseases. As an upstream signaling molecule of such abnormal vascular contraction leading to vasospasm, we previously identified sphingosylphosphorylcho- line (SPC), which induced the Ca2+-sensitization of VSM contraction in vitro and in vivo through the sequential activation of Fyn (a Src family tyrosine kinase) and ROK. The marked elevation

Muscle Contraction and Cell Motility: Fundamentals and Developments Edited by Haruo Sugi

Copyright © 2017 Pan Stanford Publishing Pte. Ltd.

ISBN 978-981-4745-16-1 (Hardcover), 978-981-4745-17-8 (eBook)

of SPC level was also observed in the vasospastic patients, indicating that SPC is a causal factor of the Ca2+-sensitization leading to vasospasm. Surprisingly we found the significant linkage between the extent of SPC-induced contraction and serum total cholesterol level in both human and rabbits. This review covers the current knowledge of the mechanisms by which SPC induces Ca2+-sensitization leading to vasospasm and the roles of cholesterol and its enriched membrane microdomains, membrane lipid rafts.

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