NADH-linked substrate dependence of peroxide-induced respiratory inhibition and calcium efflux in isolated renal mitochondria

Angelo Vlessis

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Peroxide-induced state 3 respiratory inion and Ca2+ efflux in isolated renal mitochondria exhibited a NADH-linked substrate dependence. ADP-stimulated respiratory rates in the presence of various concentrations of tert-butyl hydroperoxide (tBOOH, 0-1000 nmol/mg protein) were determined using glutamate, β-hydroxybutyrate, or pyruvate as substrates. Pyruvate-driven respiration was most sensitive to inhibition (K(i) ~ 75 nmol of tBOOH/mg protein) followed by β-hydroxybutyrate and glutamate (K (i) ~ 150 nmol/mg tBOOH/mg protein for each). Calcium (5-10 nmol/mg protein) potentiated tBOOH-induced respiratory inhibition using all three substrates. Mitochondrial Ca2+ efflux, induced by tBOOH, was most pronounced with pyruvate as substrate. Glutamate prevented Ca2+ efflux while the efflux rate with β-hydroxybutyrate was intermediate between glutamate and pyruvate. The substrate-dependent pattern of tBOOH-induced NAD(P)H (NADH plus NADPH) and cytochrome b oxidation was similar to that seen for respiratory inhibition and Ca2+ efflux suggesting that NAD(P)H may be a common factor in both responses. Low tBOOH concentrations inhibited pyruvate dehydrogenase flux while higher concentrations enhanced pyruvate dehydrogenase flux and activation. The results are discussed in relation to currently proposed theories of reactive oxygen-induced respiratory inion, Ca2+ efflux, and reperfusion injury.

Original languageEnglish (US)
Pages (from-to)1448-1453
Number of pages6
JournalJournal of Biological Chemistry
Volume265
Issue number3
StatePublished - 1990

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Mitochondria
Peroxides
Pyruvic Acid
NAD
Hydroxybutyrates
Calcium
Kidney
Glutamic Acid
Substrates
NADP
Oxidoreductases
Proteins
Fluxes
tert-Butylhydroperoxide
Cytochromes b
Respiratory Rate
Reperfusion Injury
Adenosine Diphosphate
Respiration
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

NADH-linked substrate dependence of peroxide-induced respiratory inhibition and calcium efflux in isolated renal mitochondria. / Vlessis, Angelo.

In: Journal of Biological Chemistry, Vol. 265, No. 3, 1990, p. 1448-1453.

Research output: Contribution to journalArticle

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