Manganese superoxide dismutase protects mitochondrial complex I against adriamycin-induced cardiomyopathy in transgenic mice

Hsiu Chuan Yen, Terry D. Oberley, C. Gary Gairola, Luke I. Szweda, Daret K. St. Clair

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

Adriamycin (ADR) is a potent anticancer drug that causes severe cardiomyopathy. We have previously demonstrated that ADR-induced ultrastructural mitochondrial injury in the heart was attenuated in manganese superoxide dismutase (MnSOD) transgenic mice. To further investigate the biochemical mechanisms by which MnSOD protected mitochondria against ADR- induced damage, cardiac mitochondrial function and activities were evaluated. The results showed that ADR caused significant decrease in state 3 respiration and respiratory control ratio using both complex I and II substrates in nontransgenic mice. In transgenic mice, state 3 respiration for complex I substrates remained unaffected by ADR, but was reduced for complex II substrate. Complex I activity was significantly decreased in nontransgenic, but not in transgenic mice after ADR treatment, suggesting that mitochondrial complex I is sensitive to inactivation by superoxide radicals. The activities of complex II and mitochondrial creatine kinase were decreased by ADR in both nontransgenic and transgenic mice. These results support our previous observations on the protective role of MnSOD on the ultrastructural damage of the heart after ADR treatment and extend the understanding of its mechanisms in mitochondria.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume362
Issue number1
DOIs
StatePublished - Feb 1 1999

Bibliographical note

Funding Information:
We thank the Electron Microscope laboratory for performing electron microscopy on isolated mitochondria, Ms. Joan Sempt for performing immunogold labeling, and Ms. May Fu for technical assistance on mitochondrial respiration. This study is supported by NIH Grants CA 49797, CA 59835, and HL 03544; by the Kentucky affiliate of American Heart Association; and by Veterans Administration Research Service.

Keywords

  • Adriamycin
  • Heart
  • Mitochondria
  • MnSOD

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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