慢性铝暴露对大鼠海马神经元PKC、CaMKⅡ、Ng的影响  

Effect of Chronic Aluminum Exposure on PKC,CaMK Ⅱ and Neurogranin in Hippocampus of Rat

作　　者：邢伟[1] 王彪[1] 郝凤进[1] 许金华[1] 赵岩[1] 刘素媛[1] 时利德[1] 

机构地区：[1]中国医科大学基础医学院生物化学与分子生物学教研室,沈阳110001

出　　处：《中国生物化学与分子生物学报》2007年第5期410-414,共5页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金资助项目(No.30371229)~~

摘　　要：通过研究慢性铝暴露对大鼠学习记忆和海马长时程增强(long-term potentiation,LTP)的影响,并检测海马神经元蛋白激酶C(protein kinasec,PKC)活性及Ca2+-钙调蛋白激酶Ⅱ(Ca2+-calmodulin dependent protein kinaseⅡ,CaMKⅡ)和神经颗粒素(neurogranin,Ng)蛋白表达的变化,探讨铝暴露损害学习记忆的作用机制.选用断乳后Wistar大鼠,以含有不同浓度AlCl3的蒸馏水进行饲养.3个月后,测定铝暴露组大鼠脑内和血中的铝含量;测量记录大鼠海马群体峰电位(population spike,PS)LTP;用改良Takai法测定海马神经元PKC活性变化;Western印迹法检测CaMKⅡ和Ng的蛋白表达.结果显示,与对照组相比,铝暴露组的PKC活性降低,差异有统计学意义(P<0·01);与对照组相比,铝暴露组的CaMⅡ蛋白表达降低,差异有统计学意义(P<0·05);与对照组相比,铝暴露组的Ng蛋白表达降低,且差异有统计学意义(P<0·05).实验结果说明:慢性铝暴露可以降低大鼠海马神经元PKC的活性及Ng和CaMKⅡ的蛋白表达,可能影响Ng磷酸化水平,从而影响CaM与Ng之间的亲和性,也影响Ca2+-CaM对CaMKⅡ的调节,抑制LTP的形成,损害学习记忆的功能.To investigate the mechanism of aluminum-induced impairments to learning and memory, the effects of chronic aluminum exposure on long term potentiation （LTP） were studied. The activity of protein kinase C （PKC） was determined and the Effect of aluminum on protein expressions of Ca^2＋/calmodulin dependent protein kinase Ⅱ（ CaMK Ⅱ ） and neurogranin （Ng） were detected. The ablactated Wistar rats were used to establish the chronic aluminium exposure models by the garage of AlCl3 of different concentrations in the drinking water. And 3 months later, the concentrations of aluminum in brain and blood were measured, PS （population spilke） LTP in hippocampus of the rat was recorded, and then the activity of PKC was determined by modified Takai Method. Western blotting was used to determine the protein expressions of CaMK Ⅱ and Ng in hippocampus. The PKC activity of AlCl3 exposure groups is obviously lower than that of control groups （ P 〈 0.01 ）. The protein expression of Ng in the hippocampi of AlCl3-exposure groups falls down comparing with that of control groups in a dose dependent manner （ P 〈 0.05 ）. The protein expression of CaMK Ⅱ in the hippocampi of AlClz -exposure groups is lower than that of control groups in a dose dependent manner too （ P 〈 0.05）. Chronic aluminum exposure can reduce not only the activity of PKC but also the protein expressions of CaMK Ⅱ and Ng and the phosphorylation level of Ng, thus affecting the affinity between Ng and calmodulin （CAM）. The adjustment and modulation of Ca^2＋ -CaM complex to CaMK Ⅱ were also impacted, inhibiting the formation of LTP and damaging learning and memory.

关 键 词：铝 蛋白激酶C(PKC) Ca^2+-钙调蛋白激酶Ⅱ(CaMKⅡ) 神经颗粒素(Ng) 学习记忆 

分 类 号：Q959.837[生物学—动物学]