Higenamine reduces apoptotic cell death by induction of heme oxygenase-1 in rat myocardial ischemia-reperfusion injury

被引:98
作者
Lee, Young Soo
Kang, Young Jin
Kim, Hye Jung
Park, Min Kyu
Seo, Han Geuk
Lee, Jae Heun
Yun-Choi, Hye Sook
Chang, Ki Churl [1 ]
机构
[1] Gyeongsang Natl Univ, Coll Med, Dept Pharmacol, Jinju 660751, South Korea
[2] Gyeongsang Natl Univ, Inst Hlth Sci, Jinju 660751, South Korea
[3] Seoul Natl Univ, Nat Prod Res Inst, Seoul 110460, South Korea
[4] Yeungnam Univ, Coll Med, Dept Pharmacol, Taegu 705717, South Korea
关键词
apoptosis; heme oxygenase; higenamine; ischemia reperfusion injury;
D O I
10.1007/s10495-006-7110-y
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
Pharmacological modulation of heme oxygenase (HO) gene expression may have significant therapeutic potential in oxidant-induced disorders, such as ischemia reperfusion (I/R) injury. Higenamine is known to reduce ischemic damages by unknown mechanism(s). The protective effect of higenamine on myocardial I/R-induced injury was investigated. Ligation of rat left anterior descending coronary artery for 30 min under anesthesia was done and followed by 24 h reperfusion before sacrifice. I/R-induced myocardial damages were associated with mitochondria-dependent apoptosis as evidenced by the increase of cytochrome c release and caspase-3 activity. Administration of higenamine (bolus, i.p) 1 h prior to I/R-injury significantly decreased the release of cytochrome c, caspase-3 activity, and Bax expression but up-regulated the expression of Bcl-2, HO-1, and HO enzyme activity in the left ventricles, which were inhibited by ZnPP IX, an enzyme inhibitor of HO-1. In addition, DNA-strand break-, immunohistochemical-analysis, and TUNEL staining also supported the anti-apoptotic effect of higenamine in I/R-injury. Most importantly, administration of ZnPP IX inhibited the beneficial effect of higenamine. Taken together, it is concluded that HO-1 plays a core role for the protective action of higenamine in I/R-induced myocardial injury.
引用
收藏
页码:1091 / 1100
页数:10
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