NITRIC OXIDE-MEDIATED INHIBITION OF THE MITOCHONDRIAL RESPIRATORY-CHAIN IN CULTURED ASTROCYTES

JP BOLANOS*, S PEUCHEN, SJR HEALES, JM LAND, JB CLARK

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

370 Citations (Scopus)

Abstract

The Ca2+-independent form of nitric oxide synthase was induced in rat neonatal astrocytes in primary culture by incubation with lipopolysaccharide (1 mu g/ml) plus interferon-gamma (100 U/ml), and the activities of the mitochondrial respiratory chain components were assessed. Incubation for 18 h produced 25% inhibition of cytochrome c oxidase activity. NADH-ubiquinone-1 reductase (complex I) and succinate-cytochrome c reductase (complex II-III) activities were not affected. Prolonged incubation for 36 h gave rise to a 56% reduction of cytochrome c oxidase activity and a 35% reduction in succinate-cytochrome c reductase activity, but NADH-ubiquinone-1 reductase activity was unchanged. Citrate synthase activity was not affected by any of these conditions. The inhibition of the activities of these mitochondrial respiratory chain complexes was prevented by incubation in the presence of the specific nitric oxide synthase inhibitor N-G-monomethyl-L-arginine. The lipopolysaccharide/interferon-gamma treatment of the astrocytes produced an increase in glycolysis and lactate formation. These results suggest that inhibition of the mitochondrial respiratory chain after induction of astrocytic nitric oxide synthase may represent a mechanism for nitric oxide-mediated neurotoxicity.

Original languageEnglish
Pages (from-to)910-916
Number of pages7
JournalJournal of Neurochemistry
Volume63
Issue number3
Publication statusPublished - Sep-1994
Externally publishedYes

Keywords

  • ASTROCYTES
  • LIPOPOLYSACCHARIDE
  • INTERFERON-GAMMA
  • NITRIC OXIDE SYNTHASE
  • NITRIC OXIDE
  • MITOCHONDRIAL RESPIRATORY CHAIN
  • GLIAL-CELLS
  • L-ARGININE
  • SYNTHASE
  • NEUROTOXICITY
  • SUPEROXIDE
  • DISEASE
  • PEROXYNITRITE
  • INDUCTION
  • OXIDATION
  • ISCHEMIA

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