title: Lead alters the developmental profile of the galactolipid metabolic enzymes in cultured oligodendrocyte lineage cells.
abstract: Lead is a neurotoxicant that can cause myelin deficits. Galactolipids are expressed during differentiation of oligodendrocyte lineage cells and accumulate in myelin. To examine the impact of lead on oligodendroglial differentiation, galactolipid metabolism in cultured oligodendrocyte lineage cells exposed to the metal was studied. Oligodendrocyte progenitor cells obtained from newborn rat pups were exposed to 1 microM 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 galactosyltransferase and 3'-phosphoadenosine-5'-phosphosulfate:galactocerebroside sulfotransferase, as compared to sodium-treated controls, in cultures of oligodendrocyte lineage cells following 2 days of differentiation. The activities of the galactolipid catabolic hydrolases, galactocerebroside-beta-galactosidase and arylsulfatase A, were reduced by 20%. Following 6 days of differentiation, lead-exposed cells exhibited levels of all the enzymes, except for arylsulfatase A, similar to those of the control cells. These results are consistent with the lead-induced delay of oligodendrocyte differentiation, as evidenced by the emergence of stage-specific immunochemical markers 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 reduction of arylsulfatase A in human fibroblasts caused by mis-sorting the newly-synthesized enzyme. The perturbation of galactolipid metabolism by lead during developmental maturation of oligodendrocytes may represent a contributing mechanism for lead-induced neurotoxicity.
authors.affiliation: Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ 08901-8525, USA.
authors.forename: W
authors.initials: W
authors.lastname: Deng
authors.forename: R D
authors.initials: RD
authors.lastname: Poretz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000378:metabolism; D038983:Galactolipids; D005698:Galactosylceramidase / Q000378:metabolism; D006017:Glycolipids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D009942:Organometallic Compounds / Q000633:toxicity*; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D038983:Galactolipids; D006017:Glycolipids; D009942:Organometallic Compounds; D002553:Cerebroside-Sulfatase; D005698:Galactosylceramidase; C008261:lead acetate