Nitric oxide enhances MPP(+) inhibition of complex I

FEBS Lett. 2001 Aug 24;504(1-2):50-2. doi: 10.1016/s0014-5793(01)02763-6.

Abstract

There is evidence that 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) toxicity is mediated through both inhibition of mitochondrial complex I and free radical generation. 7-Nitroindazole protects against MPTP toxicity in vitro and in vivo, and this appears to be related to its inhibition of nitric oxide (NO(*-)) synthase. We now show that the NO(*-) generator, glutathione-N-oxide, enhances the inhibitory action of 1-methyl-4-phenylpyridinium (MPP(+)) on complex I activity in brain submitochondrial particles. We propose that the NO(*-)-induced reversible inhibition of complex IV (cytochrome oxidase) potentiates the MPP(+)-induced irreversible free radical-mediated inhibition of complex I. Thus, NO(*-) may 'prime' the respiratory chain to the effects of MPP(+). These data provide evidence for an interaction between NO(*-) and MPP(+) at the level of the respiratory chain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacology*
  • Animals
  • Brain / drug effects
  • Brain / enzymology
  • Electron Transport Complex I
  • Enzyme Inhibitors / pharmacology*
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors*
  • Nitric Oxide / physiology*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Rats

Substances

  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Nitric Oxide
  • Nitric Oxide Synthase
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex I
  • 1-Methyl-4-phenylpyridinium