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

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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.

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Abbreviations

I/R:

ischemia-reperfusion

Hig:

higenamine

HO-1:

heme oxygenase-1

INF:

infarct area

LAD:

left anterior descending coronary artery

TTC:

triphenyltetrazolium chloride

TUNEL:

terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling

PN:

peroxynitrite

ZnPP IX:

zinc protoporphyrin IX

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Author notes

  1. Young Jin Kang

    Present address: Department of Pharmacology, College of Medicine, Yeungnam University, Daegu, 705-717

Authors and Affiliations

  1. Department of Pharmacology, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, 660-751, Korea

    Young Soo Lee, Young Jin Kang, Hye Jung Kim, Min Kyu Park, Han Geuk Seo, Jae Heun Lee & Ki Churl Chang

  2. Natural Products Research Institute, Seoul National University, Seoul, 110-460, Korea

    Hye Sook Yun-Choi

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  1. Young Soo Lee
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Correspondence to Ki Churl Chang.

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Lee, Y.S., Kang, Y.J., Kim, H.J. et al. Higenamine reduces apoptotic cell death by induction of heme oxygenase-1 in rat myocardial ischemia-reperfusion injury. Apoptosis 11, 1091–1100 (2006). https://doi.org/10.1007/s10495-006-7110-y

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