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

Abstract

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.

• Authors: Young Soo Lee, Young Jin Kang, Hye Jung Kim, Min Kyu Park, Han Geuk Seo, Jae Heun Lee, Hye Sook Yun-Choi, Ki Churl Chang
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 11 Issue 7 Pg. 1091-100 (Jul 2006) ISSN: 1360-8185 [Print] Netherlands
• PMID: 16703264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Antioxidants
• Bax protein, rat
• Cardiotonic Agents
• Enzyme Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• Protoporphyrins
• Tetrahydroisoquinolines
• bcl-2-Associated X Protein
• Peroxynitrous Acid
• zinc protoporphyrin
• Cytochromes c
• Cytochromes c2
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• Casp3 protein, rat
• Caspase 3
• Caspases
• Glutathione
• higenamine

Topics

• Alkaloids (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cardiotonic Agents (pharmacology)
• Caspase 3
• Caspases (metabolism)
• Cytochromes c (metabolism)
• Cytochromes c2 (metabolism)
• Enzyme Inhibitors (pharmacology)
• Glutathione (metabolism)
• Heme Oxygenase (Decyclizing) (metabolism)
• In Situ Nick-End Labeling
• Male
• Myocardial Infarction (etiology, metabolism, prevention & control)
• Myocardial Reperfusion Injury (complications, physiopathology, prevention & control)
• Oxidation-Reduction (drug effects)
• Peroxynitrous Acid (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Protoporphyrins (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Tetrahydroisoquinolines (pharmacology)
• bcl-2-Associated X Protein (metabolism)