Effect of Peroxide, Sodium, and Calcium on Brain Mitochondrial Respiration In Vitro: Potential Role in Cerebral Ischemia and Reperfusion

Angelo A. Vlessis, Linda L. Widener, Dagmar Bartos

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Mitochondrial pyruvate‐supported respiration was studied in vitro under conditions known to exist following ischemia, i.e., elevated extramitochondrial Ca2+, Na+, and peroxide. Ca2+ alone (7–10 nmol/mg) decreased state 3 and increased state 4 respiration to 81 and 141% of control values, respectively. Sodium (15 mM) and/or tert‐butyl hydroperoxide (tBOOH; up to 2,000 nmol/mg protein) alone had no effect on respiration; however, Na+ or tBOOH in combination with Ca2+ dramatically altered respiration. Respiratory inhibition induced by Ca2+ and tBOOH does not involve pyruvate dehydrogenase (PDH) inhibition since PDH flux increased linearly with tBOOH concentration (R= 0.96). Calcium potentiated tBOOH‐induced mitochondrial NAD(P)H oxidation and shifted the redox state of cytochrome b from 67 to 47% reduced. Calcium (5.5 nmol/mg) plus Na+ (15 mM) decreased state 3 and increased state 4 respiratory rates to 55 and 202% of control values, respectively. Sodium‐ as well as tBOOH‐induced state 3 inhibition required mitochondrial Ca2+ uptake because ruthenium red addition before Ca2+ addition negated the effect. The increase in state 4 respiration involved Ca2+ cycling since ruthenium red immediately returned state 4 rates back to control values. The mechanisms for the observed Ca2+‐, Na+‐, and tBOOH‐induced alterations in pyruvate‐supported respiration in vitro are discussed and a multifactorial etiology for mitochondrial respiratory dysfunction following cerebral ischemia in vivo is proposed.

Original languageEnglish (US)
Pages (from-to)1412-1418
Number of pages7
JournalJournal of neurochemistry
Volume54
Issue number4
DOIs
StatePublished - Apr 1990

Keywords

  • Brain mitochondria
  • Calcium
  • Ischemia–reperfusion injury
  • NAD(P)H oxidation
  • Peroxide metabolism
  • Sodium

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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