Murakami K, Feng G, Chen S G
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo.
J Pharmacol Exp Ther. 1993 Feb;264(2):757-61.
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.
蛋白激酶C（PKC）是介导细胞信号转导和神经元可塑性的一种重要酶。据报道，极低浓度（皮摩尔范围）的Pb++可激活大鼠脑组织中部分纯化的PKC（马尔科瓦茨和戈尔茨坦，1988年）。然而，如此低浓度下铅对PKC的激活作用仍存在争议（西蒙斯，1989年）。为阐明这一点，我们研究了铅对高度纯化的PKC亚型的影响。发现Pb++是所有三种PKC亚型（I型、II型和III型）的有效抑制剂，IC50为2至10微摩尔。对铅对PKC的这种抑制作用的特性分析表明：1）抑制作用不是由于与Ca++竞争；2）铅的作用位点在PKC的催化结构域上；3）抑制作用不依赖于激活方式（磷脂酰丝氨酸/二酰基甘油与顺式不饱和脂肪酸）；4）抑制作用完全可逆。
