Knockout mice heterozygous for Sod2 show alterations in cardiac mitochondrial function and apoptosis

Holly Van Remmen, Melissa D. Williams, Zhongmao Guo, Larry Estlack, Hong Yang, Elaine J. Carlson, Charles J. Epstein, Ting Ting Huang, Arlan Richardson

Research output: Contribution to journalArticlepeer-review

170 Scopus citations


Heart mitochondria from heterozygous (Sod2-/+) knockout mice have a 50% reduction in manganese superoxide dismutase (MnSOD) activity. The decrease in MnSOD activity was associated with increased mitochondrial oxidative damage as demonstrated by a decrease in the activities of iron sulfhydryl proteins sensitive to oxygen stress (aconitase and reduced nicotinamide adenine dinucleotide-oxidoreductase). Mitochondrial function was altered in the Sod2-/+ mice, as shown by decreased respiration by complex I and an increase in the sensitivity of the permeability transition to induction by calcium and t-butylhydroperoxide. The increased induction of the permeability transition in heart mitochondria from Sod2-/+ mice was associated with increased release of cytochrome c and an increase in DNA fragmentation. Cardiomyocytes isolated from neonatal Sod2-/+ and Sod2-/- mice were more sensitive to cell death than cardiomyocytes from Sod2+/+ mice after t-butylhydroperoxide treatment, and this increased sensitivity was prevented by inhibiting the permeability transition with cyclosporin A. These experiments demonstrate that MnSOD may play an important role in the induction of the mitochondrial pathway of apoptosis in the heart, and this appears to occur primarily through the permeability transition.

Original languageEnglish (US)
Pages (from-to)H1422-H1432
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3 50-3
StatePublished - 2001


  • Oxidative stress
  • Permeability transition

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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