l-Carnitine delays the killing of cultured hepatocytes by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Jack W. Snyder, Marlene E. Kyle, Thomas N. Ferraro

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The role of fatty acid metabolism in chemical-dependent cell injury is poorly understood. Addition of l-carnitine to the incubation medium of cultured hepatocytes delayed cell killing initiated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Protection by l-carnitine was stereospecific and observed as late as 1 h following addition of MPTP. d-Carnitine, but not iodoacetate, reversed the l-carnitine effect. Monoamine oxidase A and B activities, MPTP/N-methyl-4-phenylpyridinium levels, and MPTP-dependent loss of mitochondrial membrane potential measured by release of [3H]triphenylmethylphosphonium were not altered by addition of l-carnitine. Significant changes in MPTP-induced depletion of total cellular ATP did not occur with excess l-carnitine. Although the mechanism of cytoprotection exerted by l-carnitine remains unresolved, the data suggest that l-carnitine does not significantly alter: (i) mitochondrial-dependent bioactivation of MPTP; (ii) MPTP-dependent loss of mitochondrial membrane potential; or (iii) MPTP-mediated depletion of total cellular ATP content. We conclude that alterations of fatty acid metabolism may contribute to the toxic consequences of exposure to MPTP. Moreover, the lack of l-carnitine-mediated cytoprotection of monolayers incubated with 4-phenylpyridine or potassium cyanide suggests: (i) a link between fatty acid metabolism and mitochondrial membrane-mediated, bioactivation-dependent cell killing; and (ii) that inhibition of NADH dehydrogenase may not totally explain the mechanism of MPTP cytotoxicity.

Original languageEnglish (US)
Pages (from-to)132-138
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume276
Issue number1
DOIs
StatePublished - Jan 1990

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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