Model study on the bioreduction of paraquat, MPP+, and analogs. Evidence against a "redox cycling" mechanism in MPTP neurotoxicity

Biochem Biophys Res Commun. 1987 Sep 30;147(3):1095-104. doi: 10.1016/s0006-291x(87)80183-3.

Abstract

The ability of paraquat, MPP+, and analogs to be reduced by chemical reductants and by NADPH, as catalyzed by liver microsomes or purified NADPH cytochrome P-450 reductase, is reported. The analogs span a range of electrochemical potential, including values in-between that of paraquat and MPP+. Analogs with an Eo below -.55 V (vs. NHE) are not reduced by either the NADPH-microsomes or NADPH-reductase systems. The inability of MPP+ to be bio-reduced or to stimulate the production of superoxide during aerobic reduction is evidence against a redox-cycling (oxidant stress) role of MPP+ in MPTP neurotoxicity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium
  • Cytochrome P-450 Enzyme System / metabolism
  • Microsomes, Liver / metabolism
  • NADP / metabolism
  • Oxidation-Reduction
  • Paraquat / metabolism*
  • Pyridines / metabolism*
  • Pyridines / toxicity
  • Pyridinium Compounds / metabolism*
  • Pyridinium Compounds / toxicity
  • Structure-Activity Relationship

Substances

  • Pyridines
  • Pyridinium Compounds
  • NADP
  • Cytochrome P-450 Enzyme System
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Paraquat
  • 1-Methyl-4-phenylpyridinium