甲基苯丙胺通过L型钙通道致皮层神经元病理性蛋白APP及p⁃Tau过表达
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国家自然科学基金(81701872,81673213);江苏省自然科学基金(BK20151557)


Involvement of the L⁃type Ca2 + channel in methamphetamine⁃induced APP and p⁃Tau upregulation
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    摘要:

    目的:探讨甲基苯丙胺(methamphetamine,METH)暴露引起的阿尔兹海默病(Alzheimer’s disease,AD)样改变,阐述L型钙通道在该病理样改变中的作用。方法:借助原代培养的神经元,利用Western blot法,观察METH(0、30、100、300、1 000 μmol/L)暴露后引起AD样病理性蛋白淀粉样蛋白前体(amyloid precursor protein,APP)、磷酸化Tau蛋白(p-Tau)的表达,并观察钙通道抑制剂硝苯地平作用后APP、p-Tau表达的改变。结果:APP和p-Tau的表达随METH作用浓度和时间的增加而增高,具有剂量和时间依赖性。钙通道抑制剂硝苯地平(nifedipine,NIF)预先孵育后,METH引起的AD样改变明显改善。结论:METH暴露可引起AD病理性改变,L型钙通道抑制剂可部分逆转上述改变,因而L型钙通道可能作为对METH作用的干预靶点,具有潜在的干预价值。

    Abstract:

    Objective:To investigate the Alzheimer disease(AD)-like changes caused by methamphetamine(METH)exposure,and to elucidate the role of L-type calcium channels in this pathological change. Methods:After primary cultured neurons were exposed to METH(0,30,100,300,and 1 000 μmol/L),Western blotting assay was performed to investigate the expression of AD-like pathological protein amyloid precursor protein(APP)and p-Tau with or without the treatment of nifedipine. Results:After METH treatment,APP and p-Tau increased in a dose-dependent manner. Meanwhile,with a certain concentration of METH cultured with the neurons,the level of APP and p-Tau was increased in a time-dependent manner. After pre-incubation with the calcium channel inhibitor nifedipine(NIF),the METH-induced AD-like changes were significantly improved. Conclusion:METH exposure can cause AD pathological protein changes and L-type calcium channel ihhibitor can partially reverse the adverse changes,therefore,L-type calcium channel may be a potential intervention target for METH with the potential intervention value.

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胡 歆,吕梦倩,王 宇,蒋 雷,王 军,夏峥嵘,夏 雷.甲基苯丙胺通过L型钙通道致皮层神经元病理性蛋白APP及p⁃Tau过表达[J].南京医科大学学报(自然科学版),2019,(4):491-494

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  • 收稿日期:2018-09-28
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  • 在线发布日期: 2019-05-07
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