Molecular mechanisms underlying cytotoxic edema induced by methylmercury

甲基汞诱导细胞毒性水肿的分子机制

• 批准号: 23790157
• 负责人: HIROOKA Takashi
• 金额: $ 2.83万
• 依托单位: Tokyo University of Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790157/
• 关键词: メチル水銀; 浮腫仮説; 細胞性浮腫; ポリオール経路; アルドース還元酵素; ソルビトール脱水素酵素; p38 MAPK; Nrf2; MAPK経路; Nrf2経路

Selective damage of the cerebrum in the patients with Minamata disease is attributed to methylmercury induced-cerebral edema. The purpose of the present study was to investigate the molecular mechanisms of cytotoxic edema caused by methylmercury. Aldose reductase dysfunction in polyol pathway is known to causes cytotoxic edema. We founded that methylmercury induced aldose reductase expressionvia p38 MAPK and transcription factor Nrf2 activation in cultured human brain microvascular pericytes. These resultssuggest the possibility that induction of aldose reductase expression might be one of the molecular mechanism underling cytotoxic edema induced by methylmercury.

结论甲基汞所致的脑水肿是水俣病患者脑的选择性损害。本研究的目的是探讨甲基汞引起细胞毒性水肿的分子机制。已知多元醇途径中的醛糖还原酶功能障碍可引起细胞毒性水肿。我们发现甲基汞通过激活p38 MAPK和转录因子Nrf2诱导培养的人脑微血管周细胞表达醛糖还原酶。这些结果表明，诱导醛糖还原酶的表达可能是甲基汞诱导细胞毒性水肿的分子机制之一。

项目成果

The cytotoxicity of methylmercury in human brain microvascular endothelial cells and pericytes in culture

甲基汞对培养的人脑微血管内皮细胞和周细胞的细胞毒性

• 发表时间: 2012
• 期刊: Biol. Pharm. Bull
• 作者: Hirooka Takashi;Kaji Toshiyuki
• 通讯作者: Kaji Toshiyuki

メチル水銀がヒト脳組織において誘発する浮腫性変化のメカニズムとしてのポリオール経路の機能障害

多元醇途径功能障碍是甲基汞引起人脑组织水肿变化的机制

• 发表时间: 2012
• 作者: 津川仁;鈴木秀和;平田明成(廣岡孝志)
• 通讯作者: 平田明成(廣岡孝志)

Hypoxia potentiates the inhibitory effect of methylmercury on the repair of damaged monolayers of human microvascular endothelial cells

缺氧增强甲基汞对人微血管内皮细胞受损单层修复的抑制作用

• 发表时间: 2012
• 作者: Takahiro Tanji;Kenji Nishikori;Hirohisa Shiraishi;Masatomo Maeda;Ayako Ohashi-Kobayashi;Takashi Hirooka
• 通讯作者: Takashi Hirooka

Hypoxia potentiates the inhibitory effect of methylmercury on the repair of damaged monolayers of human brain microvascular endothelial cells

缺氧增强甲基汞对人脑微血管内皮细胞受损单层修复的抑制作用

• 作者: Wada;T.;Ihunnah;C.A.;Gao;J.;Chai;X.;Zeng;S.;Philips;B.J.;Rubin;J.P.;Marra;K.G.;and Xie;W. Mol;Takashi Hirooka
• 通讯作者: Takashi Hirooka

東京理科大学 薬学部 環境健康学

东京理科大学药学部环境健康学部