Effect of peroxide, sodium, and calcium on brain mitochondrial respiration in vitro: Potential role in cerebral ischemia and reperfusion

Angelo Vlessis, L. L. Widener, D. Bartos

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Mitochondrial pyruvate-supported respiration was studied in vitro under conditions known to exist following ischemia, i.e., elevated extramitochondrial Ca 2+, Na +, and peroxide. Ca 2+ 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 Ca 2+ dramatically altered respiration. Respiratory inhibition induced by Ca 2+ 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 Ca 2+ uptake because ruthenium red addition before Ca 2+ addition negated the effect. The increase in state 4 respiration involved Ca 2+ cycling since ruthenium red immediately returned state 4 rates back to control values. The mechanisms for the observed Ca 2+-, 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
StatePublished - 1990

Fingerprint

Brain Ischemia
Pyruvic Acid
Reperfusion
Brain
Respiration
Ruthenium Red
Oxidoreductases
Sodium
Calcium
tert-Butylhydroperoxide
Cytochromes b
Peroxides
NAD
Respiratory Rate
Fluxes
Oxidation
Oxidation-Reduction
calcium peroxide
sodium peroxide
In Vitro Techniques

Keywords

  • Brain mitochondria
  • calcium
  • ischemia-reperfusion injury
  • NAD(P)H oxidation
  • peroxide metabolism
  • sodium

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Effect of peroxide, sodium, and calcium on brain mitochondrial respiration in vitro : Potential role in cerebral ischemia and reperfusion. / Vlessis, Angelo; Widener, L. L.; Bartos, D.

In: Journal of Neurochemistry, Vol. 54, No. 4, 1990, p. 1412-1418.

Research output: Contribution to journalArticle

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