虚血および麻酔プレコンディショニングにおけるmPTP開口抑制のメカニズムの解明

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Author: 藤井, 優佳ほか

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Publication date: 2017-05-31

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Note (General)：: 金沢大学医薬保健研究域医学系心筋保護作用が知られているSTAT3と,心筋障害に関与していることが知られているCyclophilinD (CypD)の心筋細胞内での関係について検討した．STAT3の種々のリン酸化変異型を作成しCypDとの結合を調べたところ,すべての変異型とCypDは結合を認めた，心筋...

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Material Type: 文書・図像類
Title: 虚血および麻酔プレコンディショニングにおけるmPTP開口抑制のメカニズムの解明
Author/Editor: 藤井, 優佳
Fujii, Yuka
Author Heading: 藤井, 優佳
Fujii, Yuka
Publication Date: 2017-05-31
Publication Date (W3CDTF): 2017-05-31
Alternative Title: Mechanism of mPTP opening in the context of ischemic and/or anesthetic preconditioning
Periodical title: 平成28(2016)年度科学研究費補助金若手研究(B) 研究成果報告書 = 2016 Fiscal Year Final Research Report
No. or year of volume/issue: 2015-04-01 – 2017-03-31
Volume: 2015-04-01 – 2017-03-31
Pages: 4p.-
Text Language Code: jpn
Subject Heading: mitochondria
mPTP
ischemia
cardiomyocyte
Target Audience: 一般
Note (General): 金沢大学医薬保健研究域医学系
心筋保護作用が知られているSTAT3と,心筋障害に関与していることが知られているCyclophilinD (CypD)の心筋細胞内での関係について検討した．STAT3の種々のリン酸化変異型を作成しCypDとの結合を調べたところ,すべての変異型とCypDは結合を認めた，心筋細胞株虚血再灌流モデルにおいてプロポフォールおよびその溶媒脂肪乳剤添加の虚血または虚血再灌流による心筋細胞死への効果を検討したところプロポフォールおよび脂肪乳剤は細胞死を抑制することがわかった．虚血時にプロポフォールおよび脂肪乳剤がCypDのたんぱく質発現を減少させ心筋障害を減少している可能性が示唆された．
Cyclophilin D (CypD) is a known to a constituent of mitochondrial permeability transition pore (mPTP). mPTP opening is a crucial step in ischemia in the heart. We could not show any correlation between phosphorylation of STAT3 and expression of CypD in H9C2 cells as opposed to our hypothesis. I constructed several mutants of STAT3 and conducted pulldown assay but, I could not see any differences in their binding affinity to CypD.I also conducted LDL assay and the result shows propofol and lipid emulsion, which is a solvent of propofol, has inhibitory effect on ischemic cell death of H9C2 cells. Protein expression level of CypD was also decreased in H9C2 cells treated in propofol and lipid emulsion when exposed to hypoxia, but not with hypoxia-reperfusion.These results suggest that propofol and lipid emulsion have a cardio-protective effect by decreasing the expression of CypD with ischemic insult, but not with ischemia-reperfusion injury.
研究課題/領域番号:15K20035, 研究期間(年度):2015-04-01 – 2017-03-31
DOI: 10.24517/00059334
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/ja/search/?kw=20646682
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15K20035/
https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-15K20035/15K20035seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA