Effect of Cholesterol on Sphingosylphosphorylcholine-Rho-kinase -mediated Cerebral Vasospasm

2012 Fiscal Year Final Research Report

• Project/Area Number: 22791346
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Yamaguchi University
• Principal Investigator: SHIRAO Satoshi 山口大学, 大学院・医学系研究科, 助教 (70448281)
• Project Period (FY): 2010 – 2012
• Keywords: ラフト / コレステロール / スフィンゴ脂質 / 脳血管攣縮

Research Abstract

Lipid rafts are cholesterol-enriched membrane microdomains that influence signal transduction. In this study, hypercholesterolemia increased vascular smooth muscle (VSM) cholesterol (but not PC, a major component of nonraft membranes) and sphingosylphosphorylcholine(SPC)-ROK-mediated VSM contraction. Depletion of VSM cholesterol (but not PC) byβ-cyclodextrin(β-CD) inhibited SPC-induced contraction. Treatment with β-CD decreased the mean % filipin III staining intensity of Human brain VSM cells. Depletion of VSM cholesterol by β -CD also decreased the raft marker ganglioside GM1 count per unit membrane length and inhibited SPC-induced contraction. These results indicate that cholesterol potentiates SPC-ROK-mediated contractions of importance in cerebral vasospasm and are compatible with a role for lipid rafts in this process.

Research Products

• [Journal Article] Sphingosylphosphorylcholine-Rho-kinasemediated smooth muscle contraction in the rat basilar artery is regulated by the serum total cholesterol or vascular tissue cholesterol level: a mechanistic role for lipid rafts (2011)
  • Author(s): Satoshi Shirao, Hiroshi Yoneda, Mizuya Shinoyama, Yoshihiko Maeda, Hiroyasu Koizumi, Hideyuki Ishihara, Fumiaki Oka, Hirokazu Sadahiro, Sadahiro Nomura, Koji Kajiwara, and Michiyasu Suzuki
  • Journal Title: Stroke Volume: 42(3) Pages: e134
  • Peer Reviewed
• [Journal Article] Sphingosylphosphorylcholine が引き起こす脳血管攣縮におけるコレステロールの役割 (2010)
  • Author(s): 白尾敏之、米田 浩、篠山瑞也、藤井正美、野村貞宏、加藤祥一、鈴木倫保
  • Journal Title: 脳血管攣縮 Volume: 26巻 Pages: 79-81
  • Peer Reviewed
• [Presentation] コレステロールの役割について (2011)
  • Author(s): 白尾敏之
  • Organizer: 日本脳神経外科学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜)
  • Year and Date: 2011-10-14
• [Presentation] Sphingosylphosphorylcho lineRho-kinase-mediated smooth muscle contraction in the rat basilar artery is regulated by the serum total cholesterol or vascular tissue cholesterol level : amechanistic role for lipid rafts (2011)
  • Author(s): Satoshi Sirao
  • Organizer: International Stroke Conference
  • Place of Presentation: Los Angeles, California, USA
  • Year and Date: 2011-02-09
• [Presentation] くも膜下出血後の脳血管攣縮に対する前向き実態調査 STROKE 2010 (2010)
  • Author(s): 米田 浩、白尾敏之、石原秀行、末廣栄一、加藤祥一、鈴木倫保
  • Organizer: 第26回スパズム・シンポジウム
  • Place of Presentation: 岩手県民会館(岩手県盛岡)
  • Year and Date: 2010-04-15