Inhibition of brain protein kinase C subtypes by lead.
Protein kinase C (PKC) is an important enzyme in mediating cellular signal transduction and neuronal plasticity. Extremely low concentrations (picomolar range) of Pb++ have been reported to activate partially purified PKC from rat brain (Markovac and Goldstein, 1988). However, the lead activation of PKC at such low concentrations is still a matter of discussion (Simons, 1989). To clarify this point, we have examined the lead effect on highly purified PKC subtypes. Pb++ was found to be a potent inhibitor for all three PKC subtypes (types I, II and III) with IC50 of 2 to 10 microM. Characterization of this lead inhibition of PKC suggests that 1) the inhibition is not due to the competition with Ca++, 2) the site of action of lead is on the catalytic domain of PKC, 3) the inhibition is not dependent on the mode of activation (phosphatidylserine/diacylglycerol vs. cis-unsaturated fatty acid) and 4) the inhibition is totally reversible.
Murakami
K
K
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo.
Feng
G
G
Chen
S G
SG
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007854:Lead; D011493:Protein Kinase C; D002118:Calcium