The study of a new target for the effects of volatile anesthetics by immunoblotting.

通过免疫印迹研究挥发性麻醉剂作用的新靶点。

• 批准号: 20591817
• 负责人: SEKINE Syusuke
• 金额: $ 2.83万
• 依托单位: Tokyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591817/
• 关键词: イソフルラン; セボフルラン; プロポフォール; PKC-γ; リン酸化PKC-γ; PKCγ; リン酸化PKCγ; イソフルレン; セボフルレン

Aims : We examined the effects of different types of anesthetics on PKC-γ knockout mice. And we investigated the dynamics of the kinase in brain cells obtained from mice anesthetized with volatile and i.v anesthetics.Method and Results:We measured the required times for loss of righting reflex (rtfLORR) after administration of isoflurane, sevoflurane, or propofol on PKC-γ knockout mice and compared the times with those of wild-type mice. Volatile anesthetics (isoflurane and sevoflurane) significantly prolonged the rtfLORRs in PKC-γ knockout mice compared to those in wild-type mice. On the other hand, no significant difference was observed between knockout and wild-type mice treated with propofol . We also used immunoblotting to investigate the intracellular distribution of PKC-γ and phosphorylated PKC-γ (p-PKC-γ) in brain cell fractions obtained from wild-type mice during the LORR induced by these anesthetics. PKC-γ was significantly decreased in the synaptic membrane fraction (P2), whereas p-PKC-γ was significantly increased in P2. There was no significant change in the supernatant fraction (S). In propofol-treated mice, PKC-γ and p-PKC-γ showed no significant changes in P2 or S.Conclusion : Our results provide new evidence to support the possibility of the involvement of PKC-γ in the actions of volatile anesthetics.

目的：研究不同麻醉药对PKC-γ基因敲除小鼠的麻醉作用。方法和结果：我们测量了PKC-γ基因敲除小鼠给予异氟烷、七氟烷或丙泊酚后翻正反射丧失（rtfLORR）所需的时间，并与野生型小鼠的时间进行了比较。与野生型小鼠相比，挥发性麻醉剂（异氟烷和七氟烷）显著延长了PKC-γ敲除小鼠的rtfLOR。另一方面，用丙泊酚治疗的敲除小鼠和野生型小鼠之间没有观察到显著差异。我们还使用免疫印迹法研究了在这些麻醉剂诱导的LORR期间从野生型小鼠获得的脑细胞组分中PKC-γ和磷酸化PKC-γ（p-PKC-γ）的细胞内分布。PKC-γ在突触膜部分（P2）中显著降低，而p-PKC-γ在P2中显著升高。上清液级分（S）无显著变化。结论：本实验结果为PKC-γ参与挥发性麻醉药的作用提供了新的证据。

项目成果

Isoflurane inhibits protein kinase C gamma and calcium/calumoduline dependent protein kinase II-alfa translocation to synaptic membrane in ischemic mice brains.

异氟醚抑制缺血小鼠大脑中蛋白激酶 C γ 和钙/钙调蛋白依赖性蛋白激酶 II-α 易位至突触膜。

• 发表时间: 2008
• 期刊: Neurochem. Res. 33
• 作者: Shohei Matsumoto;Michihiro Murozono;Daisuke Nagaoka;Shuhei Matsuoka;Akiko Takeda;Hideyuki Narita;Seigo Watanabe;Atsushi Isshiki;Yasuo Watanabe;Koizuka S;Matsumoto S
• 通讯作者: Matsumoto S

プロテインキナーゼCγノックアウトマウスを用いた吸入麻酔薬作用機序の検討

使用蛋白激酶 Cγ 敲除小鼠研究吸入麻醉药的作用机制

• 发表时间: 2009
• 作者: Doi T;Adachi S;Takai S;Matsushima-Nishiwaki R;Kato H;Enomoto Y;Minamitani C;Otsuka T;Tokuda H;Akamatsu S;Iwama T;Kozawa O;Ogura S.;宮下亮一
• 通讯作者: 宮下亮一

Effects of different types of aneathetic arents on cellular PKC γ dynamics in mouse brain

不同类型麻醉剂对小鼠脑细胞 PKC γ 动态的影响

• 发表时间: 2011
• 期刊: Pharmacology 87巻
• 作者: Akiko Takeda;Ryoichi Miyashita;Takeo Nagura;Shusuke Sekine;Michihiro Murozono;Shohei Matsumoto;Hiroyuki Uchino
• 通讯作者: Hiroyuki Uchino

Isoflurane inhibits protein kinase C gamma and calcium/calmoduline dependent protein kinase II-alfa translocation to synaptic membrane in ischemic mice brains.

异氟醚抑制缺血小鼠大脑中蛋白激酶 C γ 和钙/钙调蛋白依赖性蛋白激酶 II-α 易位至突触膜。

• 发表时间: 2008
• 期刊: Neurochemical Res 33巻
• 作者: Shohei Matsumoto;Michihiro Murozono;Daisuke Nagaoka;Shuhei Matsuoka;Akiko Takeda;Hideyuki Narita;Seigo Watanabe;Atsushi Isshiki;Yasuo Watanabe
• 通讯作者: Yasuo Watanabe

プロテインキナーゼC-γノックアウトマウスを用いた吸入麻酔薬作用機序の検討

使用蛋白激酶 C-γ 敲除小鼠研究吸入麻醉药的作用机制

• 发表时间: 2009
• 作者: Enomoto Y;Tokuda H;et al;小幡英章;小幡英章;宮下亮一
• 通讯作者: 宮下亮一