L-carnitine delays the killing of cultured hepatocytes by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

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-phenyl-pyridinium 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.

journal_name

Arch Biochem Biophys

authors

Snyder JW,Kyle ME,Ferraro TN

doi

10.1016/0003-9861(90)90019-u

subject

Has Abstract

pub_date

1990-01-01 00:00:00

pages

132-8

issue

1

eissn

0003-9861

issn

1096-0384

pii

0003-9861(90)90019-U

journal_volume

276

pub_type

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