Wilmarth K R, Viana M E, Abou-Donia M B
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Brain Res. 1993 Nov 19;628(1-2):293-300. doi: 10.1016/0006-8993(93)90967-r.
The Ca2+/calmodulin-dependent phosphorylation of neuronal cytoskeletal proteins was studied in brain supernatants prepared from rats exposed via inhalation to 600 to 800 ppm carbon disulfide (CS2) for 14 days. Exposure to CS2 resulted in increased phosphorylation of endogenous MAP-2 and exogenously added neurofilament triplet proteins. There also was an observed increase in the autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). Slight increases in the binding of a monoclonal antibody to the alpha subunit of CaM kinase II were seen, while large increases in the binding of [125I]calmodulin to the alpha subunit of CaM kinase II also were observed. The finding of large increases in the autophosphorylation and calmodulin-binding to CaM kinase II with only slight increases in the amount of antibody-binding suggests that CS2 exposure results in increased Ca2+/calmodulin-dependent phosphorylation of proteins by inducing an increase in kinase activity.
对通过吸入600至800 ppm二硫化碳（CS2）暴露14天的大鼠所制备的脑匀浆上清液中的神经元细胞骨架蛋白的Ca2+/钙调蛋白依赖性磷酸化进行了研究。暴露于CS2导致内源性微管相关蛋白2（MAP-2）和外源性添加的神经丝三联体蛋白的磷酸化增加。还观察到Ca2+/钙调蛋白依赖性蛋白激酶II（CaM激酶II）的自身磷酸化增加。单克隆抗体与CaM激酶II的α亚基的结合略有增加，同时也观察到[125I]钙调蛋白与CaM激酶II的α亚基的结合大幅增加。抗体结合量仅略有增加，而CaM激酶II的自身磷酸化和钙调蛋白结合大幅增加，这一发现表明，CS2暴露通过诱导激酶活性增加，导致蛋白质的Ca2+/钙调蛋白依赖性磷酸化增加。
