多巴胺D2样受体激动对多巴胺能细胞自噬的调控及其机制研究

来源 :第一届自噬生物学与疾病国际研讨会(The 1st International Symposium on Autophag | 被引量 : 0次 | 上传用户:zybp821
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离体实验中,我们发现多巴胺D2样受体激动剂(普拉克索和喹吡罗)可使PC12、MES23.5、诱导分化的SH-SY5Y细胞内LC3 Ⅱ、Beclin 1蛋白水平增加,P62蛋白水平下降.但普拉克索的对映体(几乎无多巴胺受体激动活性)和未分化的SH-SY5Y(多巴胺D2样受体表达较低)未观察上述现象.特异性多巴胺D2、D3受体抑制剂存在时,普拉克索不能促使多巴胺能细胞中上述自噬相关蛋白水平增加.此外,普拉克索可使PC12细胞内钙离子及c-Fos蛋白含量增加.清除细胞内钙离子或干扰e-Fos后,普拉克索则无法提高PC12细胞的自噬水平.染色质免疫共沉淀证实c-Fos可与Beclin 1上游某个潜在的AP-1 (TGCCTCA)位点结合.荧光素酶双标实验发现普拉克索可使Beclin 1启动子活性增加,去除这个潜在的AP-1位点后则无法增加.
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