Effect of cPLA_2 inhibition on the prevention of diabetic macrovascular complication

抑制cPLA_2对预防糖尿病大血管并发症的作用

• 批准号: 21591144
• 负责人: MATSUMURA Takeshi
• 金额: $ 3万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591144/
• 关键词: エネルギー・糖代謝異常; 糖尿病大血管合併症

In the present study, we investigated the mechanism(s) of PPARγ activation by inhibiting cPLA_2 on macrophages, and the anti-atherosclerotic effect of cPLA2 inhibition in macrophages and apoE-deficient mice. We revealed that cPLA_2 inhibition induced cyclooxygenase-2 expression and subsequent 15d-PGJ_2 production, resulting PPARγ activation in macrophages. Inhibition of cPLA2 suppressed LPS-induced TNF-α and MCP-1 expression, and induced ABCA1/G1 expression. Moreover, administration of cPLA_2 inhibitor, AACOCF3 suppressed the progression of atherosclerosis in apoE-deficient mice. These results suggest that cPLA2 inhibition has anti-atherosclerotic effects, and cPLA2 may be one of the therapeutic targets for diabetic macrovascular complications.

本研究通过抑制巨噬细胞上的cPLA_2来探讨其激活过氧化物酶体增殖物激活受体γ（PPARγ）的机制，并在巨噬细胞和apoE缺陷小鼠中研究cPLA_2抑制剂的抗动脉粥样硬化作用。我们发现，抑制cPLA_2可诱导巨噬细胞表达环氧合酶-2和随后的15 d-PGJ_2产生，导致PPARγ活化。抑制cPLA 2可抑制LPS诱导的TNF-α和MCP-1表达，并诱导ABCA 1/G1表达。此外，给予cPLA_2抑制剂AACOCF 3可抑制apoE缺陷小鼠动脉粥样硬化的进展。这些结果表明，cPLA 2抑制剂具有抗动脉粥样硬化作用，cPLA 2可能是糖尿病大血管并发症的治疗靶点之一。

项目成果

Thiazolidinedione-independent activation of peroxisome proliferator-activated receptor γ is a potential target for diabetic macrovascular complications.

• DOI: 10.1111/j.2040-1124.2011.00182.x
• 发表时间: 2012-02-20
• 期刊: Journal of diabetes investigation
• 影响因子: 3.2
• 作者: Matsumura T;Taketa K;Shimoda S;Araki E
• 通讯作者: Araki E

短期血糖コントロール指標としての血中可溶性インスリン受容体αサブユニットの有用性

血可溶性胰岛素受体α亚基作为短期血糖控制指标的有用性

• 发表时间: 2010
• 作者: 本島寛之;他
• 通讯作者: 他

Telmisartan exerts anti-atherosclerotic effects by activating PPARγin macrophages

替米沙坦通过激活巨噬细胞中的 PPARγ 发挥抗动脉粥样硬化作用

• 发表时间: 2011
• 期刊: Arterioscler Thromb Vasc Biol
• 作者: Matsumura T;Kinoshita H;Ishii N;Fukuda K;Motoshima H;Senokuchi T;Taketa K;Kawasaki S;Nishimaki-Mogami T;Kawada T;Nishikawa T;Araki E
• 通讯作者: Araki E

TZDs reduce mitochondrial ROS production and enhance mitochondrial biogenesis

• DOI: 10.1016/j.bbrc.2008.11.141
• 发表时间: 2009-01-30
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Fujisawa, Kazuo;Nishikawa, Takeshi;Araki, Eiichi
• 通讯作者: Araki, Eiichi

Caloric restriction decreases ER stress in liver and adipose tissue in ob/ob mice.

热量限制可降低 ob/ob 小鼠肝脏和脂肪组织的 ER 应激。

• DOI: 10.1016/j.bbrc.2010.11.120
• 发表时间: 2011
• 期刊: Biochem Biophys Res Commun
• 作者: Tsutsumi A;Motoshima H;Kondo T;Kawasaki S;Matsumura T;Hanatani S;Igata M;Ishii N;Kinoshita H;Kawashima J;Taketa K;Furukawa N;Tsuruzoe K;Nishikawa T;Araki E
• 通讯作者: Araki E