cytochrome-c-t and higenamine

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.

Topics: Alkaloids; Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Cardiotonic Agents; Caspase 3; Caspases; Cytochromes c; Cytochromes c2; Enzyme Inhibitors; Glutathione; Heme Oxygenase (Decyclizing); In Situ Nick-End Labeling; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidation-Reduction; Peroxynitrous Acid; Proto-Oncogene Proteins c-bcl-2; Protoporphyrins; Rats; Rats, Sprague-Dawley; Tetrahydroisoquinolines