title: The acute effect of lead acetate on glucocorticoid receptor binding in C6 glioma cells.
abstract: Lead exerts significant toxic effects on the nervous system, the hematopoietic system and the kidney. Specific cellular sites of action of this environmental pollutant have not been elucidated in the central nervous system. The present investigations were conducted to test the hypothesis that lead exposure perturbs glucocorticoid-mediated events in central nervous system hormonal target tissues. Utilizing the C6 glioma cell culture model in these studies, glucocorticoid receptor binding to its cytosolic receptor was investigated. Receptor binding studies yielded a Kd= 10.5 +/- 0.5 nM and a Bmax = 486 +/- 27 fmol/mg protein in untreated cells versus a Kd = 23.1 +/- 2.6 nM and Bmax = 472 +/- 35 fmol/mg protein in cells exposed to 10 microM lead acetate for 24 h. Presence of lead in these glial cells may decrease affinity of the glucocorticoid for its receptor without affecting receptor number. Treatment with 10 microM lead acetate for 48 h, resulted in a significant reduction in glucocorticoid-regulated glycerol phosphate dehydrogenase (GPDH) specific activity. These effects were not due to cell cytotoxicity assessed as cell number growth curves, [3H]thymidine incorporation or trypan blue exclusion. In protein kinase C (PKC) activity assays, treatment of cells with sodium or lead acetate and dexamethasone indicated that both lead and dexamethasone affect the distribution of PKC. In lead-treated cells cytosolic PKC activity was reduced 48% when compared to sodium acetate treated controls. Taken together, these results suggest that acute exposure of C6 cells to lead may inhibit processes involved in glucocorticoid-mediated signal transduction events within central nervous system hormonal target cells. Lead may perturb initial glucocorticoid binding events possibly by affecting PKC-mediated phosphorylations in the glucocorticoid signal transduction system.
authors.affiliation: Environmental Toxicology Program, College of Pharmacy and Pharmaceutical Sciences, Florida A and M University, Tallahassee 32307, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Tonner
authors.forename: D I
authors.initials: DI
authors.lastname: Katz
authors.forename: A S
authors.initials: AS
authors.lastname: Heiman
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000378:metabolism; D004789:Enzyme Activation; D004790:Enzyme Induction / Q000187:drug effects; D005910:Glioma / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure*; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis / Q000378:metabolism; D007700:Kinetics; D009942:Organometallic Compounds / Q000633:toxicity*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D009942:Organometallic Compounds; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D005993:Glycerolphosphate Dehydrogenase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C008261:lead acetate