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APP17肽对糖尿病小鼠微管结构和tau蛋白磷酸化有关酶类的影响
引用本文:赵咏梅!100053,赵志炜!100053,姬志娟!100053,钱玉英!100053,孙异临,晋志高,盛树力!100053. APP17肽对糖尿病小鼠微管结构和tau蛋白磷酸化有关酶类的影响[J]. 中华老年医学杂志, 1999, 0(5)
作者姓名:赵咏梅!100053  赵志炜!100053  姬志娟!100053  钱玉英!100053  孙异临  晋志高  盛树力!100053
作者单位:北京宣武医院脑老化研究实验室(赵咏梅!100053,赵志炜!100053,姬志娟!100053,钱玉英!100053,盛树力!100053),北京市神经外科研究所(孙异临),中国中医研究院针灸所(晋志高)
基金项目:北京脑老化研究实验室课题
摘    要:
目的 观察APP17 肽对糖尿病小鼠微管结构及tau 蛋白磷酸化有关酶类变化的影响。 方法 用链脲佐菌素(STZ)诱发小鼠糖尿病模型,并皮下注射APP17 肽对糖尿病小鼠进行保护。4周后,小鼠灌注固定。取各组小鼠的海马CA1 区组织进行光镜和电镜观察。行冰冻切片,做糖原合成激酶(GSK3)、细胞周期动态激酶(CDK5)、蛋白磷酸酶1(PP1)、蛋白磷酸酶2A(PP2A)、微管蛋白(tubulin)免疫组化染色。 结果 (1)糖尿病小鼠海马神经元的微管结构出现明显的断裂或溶解现象,而用APP17 肽保护可使这种现象得到明显改善;(2)糖尿病小鼠海马内表达磷酸化tau 蛋白的两种蛋白激酶GSK3、CDK5 及表达脱tau 蛋白磷酸化的磷酸酯酶PP1、PP2A 均明显减少,用APP17 肽保护的糖尿病小鼠上述酶类表达均恢复至正常水平。 结论 糖尿病小鼠脑组织代谢紊乱,蛋白质合成降低。APP17 肽可能是一种能量代谢激动剂,通过保持糖尿病小鼠海马神经元tau 蛋白的正常磷酸化而维护微管的正常结构。

关 键 词:糖尿病  能量代谢  微管  淀粉样β蛋白前体

The effect of APP peptide on microtubular structure and enzymes related to phosphorylation of tau proteins in diabetic mice
ZHAO Yongmei,ZHAO Zhiwei,JI Zhijuan,et al.. The effect of APP peptide on microtubular structure and enzymes related to phosphorylation of tau proteins in diabetic mice[J]. Chinese Journal of Geriatrics, 1999, 0(5)
Authors:ZHAO Yongmei  ZHAO Zhiwei  JI Zhijuan  et al.
Affiliation:ZHAO Yongmei,ZHAO Zhiwei,JI Zhijuan,et al. Beijing Research Laboratory for Brain Aging,Beijing Xuanwu Hospital,Beijing 100053
Abstract:
Objective To study the changes in microtubular structure and enzymes related to phosphorylation of tau proteins in diabetic mice and observe the effects of APP 17 peptide on the foregoing changes. APP 17 peptide is the 319 335 peptide sequence of beta amyloid precursor protein. Methods Mouse diabetic model was produced with streptozotocin and APP 17 peptide was injected subcutaneously as a protective. Four weeks later,fixative was injected intravascularly into the mice. Tissue specimens for each group were removed from the hippocampus CA1 area for light and electron microscopy studies. Cryostat sections were studied with immunohistochemistry for glycogen synthase kinase 3(GSK 3),cyclic dynamic kinase 5 (CDK 5),protein phosphatase 1 (PP 1) ,protein phosphatase 2A (PP 2A),and tubulin. Results (1) The microtubules of hippocampal neurons of diabetic mice showed pronounced changes of fragmentation and dissolution,while the use of APP 17 peptide can significantly ameliorate these changes.(2)The hippocampal neurons of diabetic mice showed significant intracellular decrease in the two different kinds of tau phosphokinase,GSK 3 and CDK 5,and in the tau dephosphorylating enzymes,PP 1 and PP 2A. Protection with APP 17 peptide normalizes the expression of the foregoing enzymes in diabetic mice. Conclusions APP 17 peptide maintains the structural integrity of mictrotubules through preserving a normal state of phosphorylation of tau protein in hippocampal neurons of diabetic mice. Brain tissue of diabetic mice shows decrease in protein synthesis; APP 17 peptide is probably an energy agonist and can ameliorate all the metabolic abnormalities of diabetic mice.
Keywords:Diabetes mellitus Energy metabolism Microtubule Amyloid beta protein precursor
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