Faculty Collaboration Database

Paradoxical effects of metalloporphyrins on doxorubicin-induced apoptosis: scavenging of reactive oxygen species versus induction of heme oxygenase-1. Free Radic Biol Med 2002 Oct 01;33(7):988

Date

10/04/2002

Pubmed ID

12361808

DOI

10.1016/s0891-5849(02)00989-9

Scopus ID

2-s2.0-0036801924 (requires institutional sign-in at Scopus site)   60 Citations

Abstract

The cytoprotective effects of redox-active metalloporphyrins (e.g., FeTBAP and MnTBAP) were generally attributed to their ability to scavenge reactive oxygen and nitrogen species. In this study, we evaluated the pro- and antiapoptotic potentials of different metalloporphyrins containing iron, cobalt, zinc, and manganese in adult rat cardiomyocytes exposed to doxorubicin (DOX), an anticancer drug that forms superoxide and hydrogen peroxide via redox-cycling of DOX semiquinone in the presence of molecular oxygen. We used electron spin resonance/spin trapping and cytochrome c reduction to assess the scavenging of superoxide anion by metalloporphyrins. Superoxide anion was effectively scavenged by FeTBAP and MnTBAP but not by CoTBAP and ZnTBAP. FeTBAP efficiently scavenged H(2)O(2). Both CoTBAP and FeTBAP inhibited DOX-induced cardiomyocyte apoptosis. These findings implicate that mechanisms other than oxy-radical scavenging may account for their antiapoptotic property. In addition, CoTBAP and FeTBAP induced heme oxygenase-1 more potently than did MnTBAP and ZnTBAP. Inhibition of heme oxygenase abolished the protective effect of CoTBAP and reduced the protection by FeTBAP against DOX-induced cardiomyocyte apoptosis. We propose that metalloporphyrins can inhibit apoptosis either by inducing heme oxygenase-1 and antiapoptotic protein signaling or by scavenging reactive oxygen species.

Author List

Konorev EA, Kotamraju S, Zhao H, Kalivendi S, Joseph J, Kalyanaraman B

Author

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Doxorubicin
Electron Spin Resonance Spectroscopy
Free Radical Scavengers
Heart
Heart Ventricles
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Kinetics
Male
Metalloporphyrins
Muscle Cells
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Superoxides