S-Space College of Medicine/School of Medicine (의과대학/대학원) Pharmacology (약리학전공) Journal Papers (저널논문_약리학전공)
In vivo hyperoxic preconditioning prevents myocardial infarction by expressing bcl-2
- Issue Date
- Exp Biol Med (Maywood) 231:463-472
- Animals ; DNA Fragmentation ; Gene Expression Regulation ; In Situ Nick-End Labeling ; Male ; Myocardial Infarction/*prevention & control ; Myocardial Reperfusion Injury/metabolism ; Myocardium/metabolism ; NF-kappa B/metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Hyperoxia
- Preconditioning with oxidative stress has been demonstrated in vitro to stimulate the cellular adaptation to subsequent severe oxidative stress. However, it is uncertain whether this preconditioning works in vivo. In the present study, we examined in vivo the beneficial effect of oxidative preconditioning. After rats were pretreated with whole-body hyperoxygenation (100% O(2) at 3 atmosphere for 20 mins, four cycles with 20-min intermission), isolated hearts were subjected to 45-min ischemia followed by 90-min reperfusion. This hyperoxic preconditioning significantly reduced infarct size, cytochrome-c release, DNA fragmentation, and terminal deoxynucleotidyl transferase-mediated dUTD nick-end labeling-positive cell frequency in the left ventricle, biphasically with an early (30-min) and a delayed (48-hr) effect after the hyperoxygenation. Mechanistically, the NF-kappaB activity and Bcl-2 expression were enhanced in the hearts, and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, abolished the Bcl-2 induction as well as the infarct-limiting effect. An antioxidant, N-acetylcysteine, and protein kinase C (PKC) inhibitors chelerythrine and Go 6983 also blocked the preconditioning effects. These results indicate that hyperoxia induces myocardial tolerance against ischemia-reperfusion injury in association with Bcl-2 induction by NF-kappaB activation through reactive oxygen species and PKC-dependent signaling pathway.
- 1535-3702 (Print)
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