IA-2 modulates dopamine secretion in PC12 cells.

IA-2 modulates dopamine secretion in PC12 cells.
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DOI:
10.1016/j.mce.2009.09.023
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发表时间:
2010-02-05
影响因子:
4.1
通讯作者:
Notkins, Abner Louis
Notkins, Abner Louis
中科院分区:
医学2区
文献类型:
--
作者:
Nishimura, Takuya;Harashima, Shin-ichi;Hu Yafang;Notkins, Abner Louis

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胰岛素从β细胞的分泌受致密核心囊泡跨膜蛋白IA-2的表达调节。由于IA-2存在于全身的神经内分泌细胞中,因此开始本实验以确定IA-2的表达是否也调节神经递质的分泌。使用多巴胺分泌的嗜铬细胞瘤细胞系PC 12,我们发现IA-2的过度表达增加了细胞内多巴胺的含量和分泌,而通过siRNA敲低IA-2则降低了细胞内多巴胺的含量和分泌。IA-2的过表达或敲低均不影响PC 12细胞对[H3]多巴胺的摄取,但确实影响[H3]多巴胺的分泌量。IA-2的过表达还增加了致密核心囊泡相关蛋白Rab 3A、IA-2β和分泌颗粒蛋白II的水平,而IA-2的敲低降低了这些蛋白的水平。我们的结论是,IA-2的表达深刻地影响致密核心囊泡的功能,并有广泛的调节作用,对细胞内容物和分泌的激素和神经递质。
The secretion of the hormone insulin from beta cells is modulated by the expression of the dense core vesicle transmembrane protein IA-2. Since IA-2 is found in neuroendocrine cells throughout the body, the present experiments were initiated to determine whether the expression of IA-2 also modulates the secretion of neurotransmitters. Using the dopamine-secreting pheochromocytoma cell line PC12, we found that the overexpressions of IA-2 increased the cellular content and secretion of dopamine, whereas the knockdown of IA-2 by siRNA decreased the cellular content and secretion of dopamine. Neither the overexpression nor knockdown of IA-2 influenced the uptake of [H3]dopamine by PC12 cells, but did influence the amount of [H3]dopamine secreted. Overexpression of IA-2 also increased the level of the dense core vesicle-associated proteins Rab3A, IA-2β and secretogranin II, whereas the knockdown of IA-2 decreased the level of these proteins. We conclude that the expression of IA-2 profoundly influences the function of dense core vesicles and has a broad modulating effect on the cellular content and secretion of both hormones and neurotransmitters.
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