氯丙烯对神经细胞内Ca^(2+),游离钙调蛋白,环腺苷酸含量和钙/钙调蛋白依赖性蛋白激酶Ⅱ活性的影响  

Effects of allyl chloride on intracellular Ca 2+ , Ca 2+ free calmodulin, cyclic AMP contents and Ca 2+ /calmodulin dependent protein kinase Ⅱ activity

作　　者：谢克勤[1] 孙克任[1] 高树君[1] 张磊[1] 

机构地区：[1]山东医科大学毒理学研究室

出　　处：《中国药理学与毒理学杂志》1997年第4期298-301,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金

摘　　要：用培养的鸡胚脑神经细胞研究了１．０２和２．０４ｍｍｏｌ·Ｌ－１氯丙烯作用２４ｈ后细胞内Ｃａ２＋，游离钙调蛋白（ＣａＭ）和环腺苷酸（ｃＡＭＰ）含量及钙／钙调蛋白依赖性蛋白激酶Ⅱ（Ｃａ２＋／ＣａＭ－ＰＫⅡ）活性的改变．结果显示，随着氯丙烯浓度的增加，细胞内Ｃａ２＋分别增加了４．２和６．２倍，ｃＡＭＰ含量增加了２２％和３９％，Ｃａ２＋／ＣａＭ－ＰＫⅡ活性增加了２．８和５．０倍（Ｐ＜０．０１）；而游离ＣａＭ含量则分别减少了５５％和６９％（Ｐ＜０．０１）．结果提示氯丙烯引起病理性神经轴浆内微管和神经微丝堆积与细胞内Ｃａ２＋增加有关．这可能由于细胞内Ｃａ２＋增加，激活ＣａＭ，继而激活Ｃａ２＋／ＣａＭ－ＰＫⅡ，催化微管相关蛋白２和ｔａｕ－蛋白磷酸化，抑制微管组装，使解聚的微管堆积在轴浆内．Using nerve cells from chicken embryo,the effects of allyl chloride on intracellular Ca 2+ , Ca 2+ free calmodulin(CaM) , cyclic AMP(cAMP) contents and Ca 2+ /CaM dependent protein kinase Ⅱ (Ca 2+ /CaM PK Ⅱ) activity were studied. The results showed that as allyl chloride at the concentrations of 1.02 and 2.04 mmol·L 1 added, the contents of Ca 2+ were increased by 4.2 and 6.2 times, cAMP was lifted 22% and 39%, and the activity of Ca 2+ /CaM PK Ⅱ was raised over 2.8 and 5.0 times, compared with the control, respectively(P<0.01). However, the content of Ca 2+ free CaM was markedly decreased by 55% and 69% (P<0.01). The results suggest that the allyl chloride induced accumulations of microtubule and neurofilament in pathological nerve axon may be related to the intracellular Ca 2+ increase, that increased Ca 2+ in cells activates CaM and Ca 2+ /CaM PK Ⅱ, and then induces the microtubule associated protein 2 and tau protein phosphorylation, and eventually inhibits the assembly of microtubule and results in the accumulation of the disassembled microtubule in the nerve axon.

关 键 词：氯丙烯 神经元 钙 钙调蛋白 环腺苷酸 毒理学 

分 类 号：R996[医药卫生—毒理学]