Propofol protects the autophagic cell death induced by the ischemia/reperfusion injury in rats

被引：66
作者：
Noh, Hae Sook [1 ]
Shin, Il Woo [2 ]
Ha, Ji Hye [1 ]
Hah, Young-Sool [3 ]
Baek, Seon Mi [1 ]
Kim, Deok Ryong [1 ]
机构：
[1] Gyeongsang Natl Univ, Sch Med, Dept Biochem, Jinju 660751, South Korea
[2] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Jinju 660751, South Korea
[3] Gyeongsang Natl Univ, Clin Res Inst, Jinju 660751, South Korea
来源：
MOLECULES AND CELLS | 2010年 / 30卷 / 05期
关键词：
autophagy; Beclin-1/Bcl-2; interaction; cell death; ischemia/reperfusion; propofol; APOPTOSIS; BECLIN; ACTIVATION; MECHANISMS; MYOCYTES; BNIP3; HEART; H9C2;
D O I：
10.1007/s10059-010-0130-z
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：455 / 460
页数：6
相关论文
共 21 条
[1]   Diphtheria toxin-induced autophagic cardiomyocyte death plays a pathogenic role in mouse model of heart failure [J].
Akazawa, H ;
Komazaki, S ;
Shimomura, H ;
Terasaki, F ;
Zou, YZ ;
Takano, H ;
Nagai, T ;
Komuro, I .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (39) :41095-41103
[2]   Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardiomyocyte-derived cell line H9c2 [J].
Aki, T ;
Yamaguchi, K ;
Fujimiya, T ;
Mizukami, Y .
ONCOGENE, 2003, 22 (52) :8529-8535
[3]   The reduced catalase expression in TrkA-induced cells leads to autophagic cell death via ROS accumulation [J].
Dadakhujaev, Shorafidinkhuja ;
Noh, Hae Sook ;
Jung, Eun Joo ;
Hah, Young-Sool ;
Kim, Chang Jae ;
Kim, Deok Ryong .
EXPERIMENTAL CELL RESEARCH, 2008, 314 (17) :3094-3106
[4]   Molecular basis of Bcl-xL's target recognition versatility revealed by the structure of Bcl-xL in complex with the BH3 domain of beclin-1 [J].
Feng, Wei ;
Huang, Siyi ;
Wu, Hao ;
Zhang, Mingjie .
JOURNAL OF MOLECULAR BIOLOGY, 2007, 372 (01) :223-235
[5]   Determination of in vitro antioxidant and radical scavenging activities of propofol [J].
Gülçin, I ;
Alici, HA ;
Cesur, M .
CHEMICAL & PHARMACEUTICAL BULLETIN, 2005, 53 (03) :281-285
[6]   Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy [J].
Hamacher-Brady, A. ;
Brady, N. R. ;
Logue, S. E. ;
Sayen, M. R. ;
Jinno, M. ;
Kirshenbaum, L. A. ;
Gottlieb, R. A. ;
Gustafsson, A. B. .
CELL DEATH AND DIFFERENTIATION, 2007, 14 (01) :146-157
[7]   The interplay hetween pro-death and pro-survival signaling pathways in myocardial ischemia/reperfusion injury: Apoptosis meets autophagy [J].
Hamacher-Brady, Anne ;
Brady, Nathan Ryan ;
Gottlieb, Roberta Anne .
CARDIOVASCULAR DRUGS AND THERAPY, 2006, 20 (06) :445-462
[8]   Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes [J].
Hamacher-Brady, Anne ;
Brady, Nathan R. ;
Gottlieb, Roberta A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (40) :29776-29787
[9]   Propofol limits rat myocardial ischemia and reperfusion injury with an associated reduction in apoptotic cell death in vivo [J].
Jin, Yong Chun ;
Kim, WooYeol ;
Ha, Yu Mi ;
Shin, Il Woo ;
Sohn, Ju Tae ;
Kim, Hye Jung ;
Seo, Han Geuk ;
Lee, Jea Heun ;
Chang, Ki Churl .
VASCULAR PHARMACOLOGY, 2009, 50 (1-2) :71-77
[10]   Myocytes die by multiple mechanisms in failing human hearts [J].
Kostin, S ;
Pool, L ;
Elsässer, A ;
Hein, S ;
Drexler, HCA ;
Arnon, E ;
Hayakawa, Y ;
Zimmermann, R ;
Bauer, E ;
Klövekorn, WP ;
Schaper, J .
CIRCULATION RESEARCH, 2003, 92 (07) :715-724
123