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钙库操纵型钙离子通道阻断剂抑制脂多糖诱导的星形胶质细胞激活。

Store-operated Ca2+ channels blockers inhibit lipopolysaccharide induced astrocyte activation.

机构信息

Department of Physiology, Guangzhou Medical University, Guangzhou, People's Republic of China.

出版信息

Neurochem Res. 2013 Oct;38(10):2216-26. doi: 10.1007/s11064-013-1130-0. Epub 2013 Aug 23.

Abstract

The destruction of calcium homeostasis is an important factor leading to neurological diseases. Store-operated Ca(2+) (SOC) channels are essential for Ca(2+) homeostasis in many cell types. However, whether SOC channels are involved in astrocyte activation induced by lipopolysaccharide (LPS) still remains unknown. In this study, we used LPS as an exogenous stimulation to investigate the role of SOC channels in astrocyte activation. Using calcium imaging technology, we first found that SOC channels blockers, 1-[h-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365) and 2-aminoethyldiphenyl borate (2-APB), inhibited LPS induced [Ca(2+)]i increase, which prompted us to speculate that SOC channels may be involved in LPS induced astrocyte activation. Further experiments confirmed our speculation shown as SOC channels blockers inhibited LPS induced astrocyte activation characterized as cell proliferation by MTS and BrdU assay, raise in glial fibrillary acidic protein expression by immunofluorescence and Western Blot and secretion of interleukin 6 (IL-6) and interleukin 1β (IL-1β) by ELISA. So, our studies showed that SOC channels are involved in LPS-induced astrocyte activation.

摘要

钙稳态的破坏是导致神经退行性疾病的一个重要因素。储存操纵钙(SOC)通道对于许多细胞类型中的钙稳态是必不可少的。然而,SOC 通道是否参与脂多糖(LPS)诱导的星形胶质细胞激活仍然未知。在这项研究中,我们使用 LPS 作为外源性刺激来研究 SOC 通道在星形胶质细胞激活中的作用。使用钙成像技术,我们首先发现 SOC 通道阻断剂 1-[h-[3-(4-甲氧基苯基)丙氧基]-4-甲氧基苯乙基]-1H-咪唑(SKF-96365)和 2-氨基乙基二苯硼酸盐(2-APB)抑制了 LPS 诱导的[Ca(2+)]i 增加,这促使我们推测 SOC 通道可能参与 LPS 诱导的星形胶质细胞激活。进一步的实验证实了我们的推测,SOC 通道阻断剂抑制了 LPS 诱导的星形胶质细胞激活,其特征为 MTS 和 BrdU 测定法中的细胞增殖、免疫荧光和 Western Blot 中神经胶质纤维酸性蛋白表达的增加以及 ELISA 中白细胞介素 6 (IL-6) 和白细胞介素 1β (IL-1β) 的分泌。因此,我们的研究表明 SOC 通道参与 LPS 诱导的星形胶质细胞激活。

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