Lead alters the developmental profile of the galactolipid metabolic enzymes in cultured oligodendrocyte lineage cells

Lead is a neurotoxicant that can cause myelin deficits. Galactolipids are e xpressed during differentiation of oligodendrocyte lineage cells and accumu late in myelin. To examine the impact of lead on oligodendroglial different iation, galactolipid metabolism in cultured oligodendrocyte lineage cells e xposed to the metal was studied. Oligodendrocyte progenitor cells obtained from newborn rat pups were exposed to 1 muM lead acetate for 24 h prior to maintenance of the cells in medium containing the metal salt for 0, 2, or 6 days of differentiation. Lead caused approximately 50% reduction in levels of the galactolipid biosynthetic transferases, UDP-galactose:ceramide gala ctosyltransferase and 3-phosphoadenosine-5'-phosphosulfate:galactocerebrosi de sulfotransferase, as compared to sodium-treated controls, in cultures of oligodendrocyte lineage cells following 2 days of differentiaition. The ac tivities of the galactolipid catabolic hydrolases, galactocerebroside-beta -galactosidase and arylsulfatase A, were reduced by 20%. Following 6 days o f differentiation, lead-exposed cells exhibited levels of all the enzymes, except for arylsulfatase A, similar to those of the control cells. These re sults are consistent with the lead-induced delay of oligodendrocyte differe ntiation, as evidenced by the emergence of stage-specific immunochemical ma rkers and the observed change in the developmental activity profile of 2',3 '-cyclic nucleotide 3'-phosphohydrolase. The activity of arylsulfatase A in lead-treated 6-day oligodendrocytes was significantly less than that found in control cultures. This effect is consistent with the lead-induced reduc tion of arylsulfatase A in human fibroblasts caused by mis-sorting the newl y-synthesized enzyme. The perturbation of galactolipid metabolism by lead d uring developmental maturation of oligodendrocytes may represent a contribu ting mechanism for lead-induced neurotoxicity. (C) 2001 Elsevier Science In c. All rights reserved.