Propofol protects the autophagic cell death induced by the ischemia/reperfusion injury in rats.
Autophagy has been implicated in cardiac cell death during ischemia/reperfusion (I/R). In this study we investigated how propofol, an antioxidant widely used for anesthesia, affects the autophagic cell death induced by the myocardial I/R injury. The infarction size in the myocardium was dramatically reduced in rats treated with propofol during I/R compared with untreated rats. A large number of autophagic vacuoles were observed in the cardiomyocytes of I/R-injured rats but rarely in I/R-injured rats treated with propofol. While LC3-II formation, an autophagy marker, was up-regulated in the I/R-injured myocardium, it was significantly down-regulated in the myocardial tissues of I/R-injured and propofol-treated rats. Moreover, propofol inhibited the I/R-induced expression of Beclin-1, and it accelerated phosphorylation of mTOR during I/R and Beclin-1/Bcl-2 interaction in cells, which indicates that it facilitates the inhibitory pathway of autophagy. These data suggest that propofol protects the autophagic cell death induced by the myocardial I/R injury.
Noh
Hae Sook
HS
Department of Biochemistry, Gyeongsang National University School of Medicine, Jinju, 660-751, Korea.
Shin
Il Woo
IW
Ha
Ji Hye
JH
Hah
Young-Sool
YS
Baek
Seon Mi
SM
Kim
Deok Ryong
DR
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D015536:Down-Regulation; D008297:Male; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015742:Propofol / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D015742:Propofol; D019253:Proto-Oncogene Proteins c-bcl-2; D058570:TOR Serine-Threonine Kinases; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C546845:mTOR protein, rat