Trivalent Chromium Induces Autophagy by Activating Sphingomyelin Phosphodiesterase 2 and Increasing Cellular Ceramide Levels in Renal HK2 Cells

博士 === 國立中興大學 === 生物醫學研究所 === 105 === Recently, autophagy has emerged as a major cell response to metabolic stress, drug toxicity, environmental pollutants and lipogenetic disturbance. Most of effort has focused on the proteins and protein interaction in autophagosome formation. However, the role of...

Full description

Bibliographic Details
Main Authors: Cheng-Lin Yang, 楊承琳
Other Authors: Kuan-Chih Chow
Format: Others
Language:en_US
Published: 2017
Online Access:http://ndltd.ncl.edu.tw/handle/92502930268140989690
Description
Summary:博士 === 國立中興大學 === 生物醫學研究所 === 105 === Recently, autophagy has emerged as a major cell response to metabolic stress, drug toxicity, environmental pollutants and lipogenetic disturbance. Most of effort has focused on the proteins and protein interaction in autophagosome formation. However, the role of lipids has not been investigated. 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. Our recent studies found that signals of ceramide overlapped with LC3 demonstrated by confocal immunofluorescence microscopy study, 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.