Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / antagonists & inhibitors
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Autophagy / drug effects*
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Beclin-1
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Down-Regulation
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Male
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Microtubule-Associated Proteins / antagonists & inhibitors
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Microtubule-Associated Proteins / metabolism
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Myocardial Reperfusion Injury / drug therapy
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Myocardial Reperfusion Injury / genetics
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Myocardial Reperfusion Injury / metabolism
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Myocardial Reperfusion Injury / pathology*
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Propofol / pharmacology*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Rats
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Rats, Sprague-Dawley
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Reperfusion Injury / drug therapy
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Reperfusion Injury / genetics
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Reperfusion Injury / metabolism
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Reperfusion Injury / pathology*
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism
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Up-Regulation
Substances
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Apoptosis Regulatory Proteins
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Beclin-1
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Becn1 protein, rat
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LC3 protein, rat
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Microtubule-Associated Proteins
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Proto-Oncogene Proteins c-bcl-2
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mTOR protein, rat
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TOR Serine-Threonine Kinases
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Propofol