BDM inhibition of cardiac mitochondrial respiration

R. C. Scaduto, L. W. Grotyohann

Research output: Contribution to journalArticle

Abstract

BDM (Butanedione monoxime) was used to suppress work output by the Langendorff perfused rat heart. Hearts were perfused with buffer containing BDM and elevated concentrations of perfusate calcium (BDM plus Ca2+) in order to maintain rates of cardiac work and oxygen consumption at levels identical to hearts perfused with a normal calcium concentration (control). BDM plus Ca2+ hearts displayed higher levels of NADH surface fluorescence, indicating an activating effect of calcium on mitochondrial enzymes. BDM plus Ca2+ hearts, however, displayed 20% lower tissue levels of phosphocreatine (PCr). Isolated mitochondria were incubated with BDM to study this effect. BDM suppressed rates of State 3 respiration. Fifty percent inhibition occurred with 5 mM BDM. Uncoupled and State 4 respiration rates were not affected. Similar results were obtained with mitochondria from liver. Steady state levels of mitochondrial NADH were not affected at any respiration rate. Double inhibitor experiments with BDM and carboxyatractyloside (CAT) were performed to identify the site of BDM inhibition. Low levels of BDM (0 to 5 mM) suppressed respiration in a near linear fashion. In the presence of CAT, at levels which inhibit respiration by 60%, low levels of BDM were without effect. The fact the effects of BDM and CAT were not additive indicates that BDM does not inhibit adenine nucleotide transport. These data indicate that BDM inhibits oxidative phosphorylation at a site on the mitochondrial ATPase.

Original languageEnglish (US)
Pages (from-to)A999
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Scaduto, R. C., & Grotyohann, L. W. (1998). BDM inhibition of cardiac mitochondrial respiration. FASEB Journal, 12(5), A999.