镧对大鼠海马CA3区cAMP应答元件结合蛋白磷酸化和及刻早期基因表达的影响  

Effects of lanthanum on the phosphorylation of cAMP response element binding protein and expression of immediate early genes in the hippocampual CA3 area of rats

作　　者：杨敬华[1] 刘秋芳[1] 巫生文[1] 张立丰[1] 齐鸣[1] 鲁帅[1] 蔡原[1] 

机构地区：[1]中国医科大学公共卫生学院卫生毒理学教研室,沈阳110001

出　　处：《卫生研究》2011年第3期299-303,311,共6页Journal of Hygiene Research

基　　金：国家自然科学基金资助项目(No.30800925);辽宁省科技厅基金资助项目(No.2005225008-3)

摘　　要：目的研究镧(La)对大鼠海马CA3区钙调蛋白(CaM)活性、钙调蛋白依赖性蛋白激酶IV(CaMKIV)和cAMP应答元件结合蛋白(CREB)磷酸化以及c-fos、c-jun和egr1基因表达的影响。方法 40只成年雌性大鼠随机分成对照组和低、中、高剂量LaCl3染毒组,LaCl3组仔鼠在出生至断乳前通过母乳染毒,断乳后通过自由饮水的方式染毒1个月。采用磷酸二酯酶法检测仔鼠海马CA3区CaM活性,Western blot法检测仔鼠海马CA3区p-CaMK IV和p-CREB蛋白表达水平,RT-PCR法检测仔鼠海马CA3区c-fos、c-jun和egr1mRNA表达水平。结果各LaCl3染毒组海马CA3区CaM活性和p-CaMK IV、p-CREB蛋白表达水平均显著低于对照组,且具有一定的剂量-反应关系。低、中剂量LaCl3染毒组c-fos和c-jun mRNA表达显著低于对照组,中剂量LaCl3染毒组egr1 mRNA表达显著低于对照和低剂量LaCl3染毒组,高剂量LaCl3染毒组c-fos、c-jun和egr1 mRNA表达显著低于对照和低、中剂量LaCl3染毒组。结论镧可通过降低海马CA3区CaM活性和CaMK IV、CREB磷酸化以及c-fos、c-jun和egr1基因转录水平,从而损害大鼠的学习记忆能力。Objective To study the effects of lanthanum（La） on calmodulin（CaM） activity,phosphorylation of CaM dependent protein kinase IV（CaMK IV）,cAMP response element binding protein（CREB） and expression of c-fos,c-jun and egr1 in the hippocampal CA3 area of rats.Methods Forty Wistar rats in pregnancy were divided randomly into four groups： control,0.25%,0.5% and 1.0% LaCl3-administrated groups.After birth,pups of LaCl3-administrated groups were administrated with La by lactation before weaning,and then given with La by drinking water for one month.CaM activity was determined by phosphodiesterase.The protein expression levels of p-CaMK IV and p-CREB were measured by Western blotting,and c-fos,c-jun and egr1 mRNA expression levels were detected by RT-PCR.Results CaM activity and protein expression levels of p-CaMK IV and p-CREB in the hippocampal CA3 area of three LaCl3-administrated groups were lower significantly than those of control group,and presented dose-effect relationship to a certain extent.The expression levels of c-fos and c-jun mRNA in the hippocampal CA3 area of low and middle LaCl3-administrated groups were lower significantly than those of control group,and the expression levels of egr1 mRNA in the hippocampal CA3 area of middle LaCl3-administrated group were lower significantly than those of control and low LaCl3-administrated groups.The expression levels of c-fos,c-jun and egr1 mRNA in the hippocampal CA3 area of high LaCl3-administrated group were lower significantly than those of control,low and middle LaCl3-administrated groups.Conclusion La could decrease CaM activity,CaMK IV and CREB phosphorylation,c-fos,c-jun and egr1 mRNA expression in the hippocampal CA3 area and therefore cause learning and memory impairment of rats.

关 键 词：镧 海马 cAMP应答元件结合蛋白 

分 类 号：Q593.2[生物学—生物化学]