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三价铬通过激活鞘磷脂磷酸二酯酶2并提高肾HK2细胞中的细胞神经酰胺水平来诱导自噬。

Trivalent chromium induces autophagy by activating sphingomyelin phosphodiesterase 2 and increasing cellular ceramide levels in renal HK2 cells.

作者信息

Yang Cheng-Lin, Chiou Shiow-Her, Tai Wei-Chun, Joseph Nithila A, Chow Kuan-Chih

机构信息

Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.

Graduate Institute of Microbiology and Public Health, National Chung Hsing University, Taichung, Taiwan.

出版信息

Mol Carcinog. 2017 Nov;56(11):2424-2433. doi: 10.1002/mc.22689. Epub 2017 Sep 15.

Abstract

In this study, we examined the role of autophagy in the initiation of lipid increases in renal epithelial HK2 cells. We found that trivalent chromium [Cr(III)] induced autophagy by activating sphingomyelin phosphodiesterase 2 (SMPD2). SMPD2 increases levels of ceramide and other lipids. Confocal immunofluorescence microscopy showed that signals of ceramide overlapped with LC3, suggesting that ceramide might play an important role in the formation of autophagosome. In conclusion, our data indicate that Cr(III) induces autophagy via structural aberration of organelle membrane, in particular by the increase of lipid compositions in addition to autophagy-associated proteins.

摘要

在本研究中,我们检测了自噬在肾上皮HK2细胞脂质增加起始过程中的作用。我们发现三价铬[Cr(III)]通过激活鞘磷脂磷酸二酯酶2(SMPD2)诱导自噬。SMPD2可增加神经酰胺和其他脂质的水平。共聚焦免疫荧光显微镜显示神经酰胺信号与LC3信号重叠,提示神经酰胺可能在自噬体形成中起重要作用。总之,我们的数据表明Cr(III)通过细胞器膜的结构畸变诱导自噬,特别是除了自噬相关蛋白外,还通过脂质成分的增加来诱导自噬。

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