Correlation between lead-induced changes in cerebral ornithine decarboxylase and protein kinase C activities during development and in cultured PC 12 cells.
Exposure to lead (Pb) interferes with neurodevelopment and disturbs ornithine decarboxylase (ODC) activity. ODC the key regulatory enzyme of the polyamine pathway, is a potential substrate for protein kinase C (PKC). Therefore, we examined developmental changes in PKC activity and its relationship to ODC activity. Male rats were lactationally exposed to 0.2% Pb-acetate from birth to weaning. PKC and ODC activity were measured on postnatal days (PND) 3, 5, 10, 20 and 30. We found that the basal patterns of ODC and PKC activities resembled each other in both the neocortex and cerebellum and Pb-exposure attenuated both enzymes in a similar manner. To determine whether any link existed between these enzymes, ODC and PKC activities were induced to increase using nerve growth factor (NGF) in the presence and/or absence of ODC (difluoromethylornithine, DFMO) and PKC (staurosporine) inhibitors, in control and Pb-exposed Pheochromocytoma (PC-12) cells. Staurosporine decreased both ODC activity and PKC activity, while DFMO had no effect on PKC activity. These data suggest that ODC may be regulated by PKC and that Pb-induced developmental alterations in ODC activity may be secondary to changes in the integrity of PKC.
Hilliard
A
A
Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA.
Ramesh
A
A
Zawia
N H
NH
D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007854:Lead / Q000633:toxicity; D007855:Lead Poisoning / Q000201:enzymology*; D008297:Male; D019579:Neocortex / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D009498:Neurotoxins / Q000633:toxicity; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D016716:PC12 Cells; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D019311:Staurosporine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009498:Neurotoxins; D007854:Lead; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D019311:Staurosporine