Reduction by lead of hydrocortisone-induced glycerol phosphate dehydrogenase activity in cultured rat oligodendroglia.
Time- and dose-dependent toxic effects of lead (Pb) acetate on astroglia, oligodendroglia, and meningeal fibroblasts cultured from immature rat brain were measured. Cultures were exposed for 3 d to Pb (1, 10, and 100 microM) and then examined immediately (Day 0) or 3 or 10 d after Pb treatment was discontinued. The percentages of astroglia and fibroblasts excluding dye were unaffected by Pb, whereas the percentage of oligodendroglia excluding dye decreased significantly (P less than 0.01) at all time points after exposure to 100 microM Pb. Lead (100 microM) also reduced the total cell numbers of astroglia, oligodendroglia, and meningeal fibroblasts. Amino acid incorporation into protein by oligodendroglia was stimulated after exposure to 100 microM Pb at all time points and also by 1 and 10 microM on Day 3. Incorporation was stimulated in astroglia only on Day 0 by 10 and 100 microM. Hydrocortisone-stimulated glycerolphosphate dehydrogenase (GPDH) activity was assayed in oligodendroglia cultures. A significant decrease in specific activity was seen after a 4-d exposure to lead. Because oligodendroglia are responsible for myelin synthesis in the central nervous system, and GPDH may synthesize a precursor for myelin lipid synthesis, it was proposed that the hypomyelination observed in lead-intoxicated neonatal rats may result partially from a primary toxic effect on oligodendroglia. GPDH activity was not inhibited by Pb in mixed glial cultures containing both astroglia and oligodendroglia. This result suggests that astroglia in culture have the ability to delay the lead-induced inhibition of oligodendroglial GPDH activity and supports the hypothesis that astroglia in culture serve a protective function.
Wu
J N
JN
Department of Veterinary Anatomy, Texas A&M University, College Station 77843.
Tiffany-Castiglioni
E
E
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D003864:Depression, Chemical; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors*; D006854:Hydrocortisone / Q000037:antagonists & inhibitors*; D009457:Neuroglia / Q000201:enzymology*; D009836:Oligodendroglia / Q000187:drug effects / Q000201:enzymology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D009942:Organometallic Compounds; D005954:Glucosephosphate Dehydrogenase; C008261:lead acetate; D006854:Hydrocortisone