铅对大鼠脑突触体钙调素的抑制作用

Inhibition of lead on calmoduin of rat brain synaptosomes

用体外法,将大鼠脑突触体膜,在不同浓度的Pb^(2+)作用下分别测定CaM依赖的Ca^(2+)-ATP酶和CaM活性的IC_(50)值。结果表明,Pb^(2+)对Ca^(2+)-ATP酶活性IC_(50)为 1.62mM;对CaM活性IC_(50)为3.85mM。当向不含CaM的脑突触体加入3.0～10.0μg的外源性CaM后,被Pb^(2+)抑制的Ca^(2+)-ATP酶活性均有显著的逆转而恢复或接近正常水平。推测Pb^(2+)主要直接作用在脑突触体膜的CaM,通过CaM分子构象改变,抑制Ca^(2+)-ATP酶,这可能是铅神经毒性的分子基础。

In vitro effects of lead on Ca^(2+)-ATPase of rat brain synaptosomes in the absence andpresence of calmoduin (CaM) were studied. The rat synaptic membrances were prepared andCaM was depleted by washing with 1mM EGTA. Pb^(2+). inhibited the basal as well as CaM-stimulated Ca^(2+)-ATPase in a concentration-dependent manner, suggesting the Pb^(2+) interactionwith calcium pump. Further, the inhibition of CaM-stimulated Ca^(2+)-ATPase activity by Pb^(2+)could be reversed by excessive addition of CaM. Exogenous CaM restored the Pb^(2+) inhibitedCa^(2+)-ATPase activity approximate the original level. These results suggest that Pb^(2+) mayalter calmodulin-regalated synaptic processes in the brain and could constitute a possiblemolecular mechanism for the lead nurotoxicity.