TY - JOUR
T1 - The involvement of lipid activators of protein kinase C in the induction of zif268 in PC12 cells exposed to lead
AU - Olivi, Luisa
AU - Sisk, Jeanne
AU - Bressler, Joseph
N1 - Funding Information:
We thank Ms. Pamela D. Jones for help in manuscript preparation. This research was supported by NIH grants PO1 ES08131 (GG) and RO1 ES08785 (JB).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - 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.
AB - 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.
KW - Lead, protein kinase C
KW - Phosphatidylinositol 3-kinase
KW - zif268, diacylglycerol
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U2 - 10.1023/A:1021696011920
DO - 10.1023/A:1021696011920
M3 - Article
C2 - 12587664
AN - SCOPUS:0037267175
VL - 28
SP - 65
EP - 71
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 1
ER -