期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 724, 期 -, 页码 58-66出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2013.12.027
关键词
Sevoflurane; Preconditioning; Autophagy; Ischemia-reperfusion; Chloramphenicol
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan (Masami Miyamae) (Tokyo, Japan) [23593008]
- Grants-in-Aid for Scientific Research [23593008, 25463159] Funding Source: KAKEN
Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 mm ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 mu M) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45 + CAP). To inhibit autophagy, 3-methyladenine (10 mu M) was administered during sevoflurane administration in SEVO-45 + CAR Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained before ischemia to determine autophagy-related protein (microtubule-associated protein light chain I and II: LC3-I, II), Ala and glycogen synthase kinase 3 beta (GSK3 beta) expression using Western blot analysis. The effect of autophagy on calcium-induced mitochondrial permeability transition pore (MPTP) opening in isolated calcein-loaded mitochondria was assessed. Electron microscopy was used to detect autophagosomes. Infarct size was significantly reduced in SEVO-30, but not in SEVO-45. Chloramphenicol restored sevoflurane preconditioning lost by 45 min ischemia. There were more abundant autophagozomes and LC3-II expression was significantly increased in SEVO-45 + CAP. Induction of autophagy before ischemia enhanced GSK3 beta phosphorylation and inhibition of calcium-induced MPTP opening. These effects were abolished by 3-methyladenine. Pre-ischemic induction of autophagy restores sevoflurane preconditioning lost by longer ischemic insult. This effect is associated with enhanced inhibition of MPTP by autophagy. (C) 2013 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据