Selective inactivation of redox-sensitive mitochondrial enzymes during cardiac reperfusion

Hesham A. Sadek, Kenneth M. Humphries, Pamela A. Szweda, Luke I. Szweda

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Reperfusion of ischemic myocardial tissue results in an increase in mitochondrial free radical production and declines in respiratory activity. The effects of ischemia and reperfusion on the activities of Krebs cycle enzymes, as well as enzymes involved in electron transport, were evaluated to provide insight into whether free radical events are likely to affect enzymatic and mitochondrial function(s). An in vivo rat model was utilized in which ischemia is induced by ligating the left anterior descending coronary artery. Reperfusion, initiated by release of the ligature, resulted in a significant decline in NADH-linked ADP-dependent mitochondrial respiration as assessed in isolated cardiac mitochondria. Assays of respiratory chain complexes revealed reduction in the activities of complex I and, to a lesser extent, complex IV exclusively during reperfusion, with no alterations in the activities of complexes II and III. Moreover, Krebs cycle enzymes α-ketoglutarate dehydrogenase and aconitase were susceptible to reperfusion-induced inactivation with no decline in the activities of other Krebs cycle enzymes. The decline in α-ketoglutarate dehydrogenase activity during reperfusion was associated with a loss in native lipoic acid on the E2 subunit, suggesting oxidative inactivation. Inhibition of complex I in vitro promotes free radical generation. α-Ketoglutarate dehydrogenase and aconitase are uniquely susceptible to in vitro oxidative inactivation. Thus, our results suggest a scenario in which inhibition of complex I promotes free radical production leading to oxidative inactivation of α-ketoglutarate dehydrogenase and aconitase.

Original languageEnglish (US)
Pages (from-to)222-228
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume406
Issue number2
DOIs
StatePublished - 2002

Fingerprint

Aconitate Hydratase
Reperfusion
Oxidation-Reduction
Free Radicals
Oxidoreductases
Citric Acid Cycle
Enzymes
Electron Transport
Thioctic Acid
Ischemia
Mitochondria
Activity Cycles
Myocardial Reperfusion
NAD
Adenosine Diphosphate
Rats
Assays
Ligation
Tissue
Coronary Vessels

Keywords

  • α-Ketoglutarate dehydrogenase
  • Aconitase
  • Complex I
  • Electron transport
  • Free radicals
  • Ischemia
  • Mitochondria
  • Reperfusion

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Selective inactivation of redox-sensitive mitochondrial enzymes during cardiac reperfusion. / Sadek, Hesham A.; Humphries, Kenneth M.; Szweda, Pamela A.; Szweda, Luke I.

In: Archives of Biochemistry and Biophysics, Vol. 406, No. 2, 2002, p. 222-228.

Research output: Contribution to journalArticle

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