The involvement of lipid activators of protein kinase C in the induction of ZIF268 in PC12 cells exposed to lead.
Lead (Pb) induces the expression of immediate early genes (IEG) in PC12 cells by a mechanism that involves protein kinase C (PKC). To define the mechanisms, the involvement of two commonly observed lipid activators of PKC, diacylglycerols, and phosphatidylinositols, were examined. A dose-dependent increase in the expression of the IEG zif268 was observed in PC12 cells exposed to Pb. The PKC inhibitor Ro-31-8220 blocked the induction. An increase in levels of diacylglycerols was observed in PC12 cells exposed to Pb, but the increase was inhibited by Ro-31-8220. The phosphatidylinositol 3-kinase inhibitor Wortmannin, but not the inhibitor LY 294002, blocked the induction zif268 in Pb-exposed cells. Small increases in phosphatidylinositol 3-kinase activity were observed after exposure to Pb. In summary, diacylglycerols are elevated in PC12 cells exposed to Pb by a mechanism that requires PKC. It is possible that diacylglycerols contribute to the induction of zif268 by Pb by sustaining PKC activation.
Olivi
Luisa
L
Kennedy Krieger Research Institute, Baltimore, Maryland 21205, USA.
Sisk
Jeanne
J
Bressler
Joseph
J
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004075:Diglycerides / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017874:Immediate-Early Proteins; D007211:Indoles / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D016716:PC12 Cells; D010716:Phosphatidylinositols / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D004268:DNA-Binding Proteins; D004075:Diglycerides; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D007211:Indoles; D009025:Morpholines; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; D007854:Lead; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011493:Protein Kinase C; C064758:Ro 31-8220; D000077191:Wortmannin