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

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


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.

Keywords: ATAD3A; autophagy; ceramide; dihydrodiol dehydrogense; reactive oxygen species; sphingomyelin phosphodiesterase 2.

MeSH terms

  • Autophagy / drug effects*
  • Cell Line
  • Ceramides / metabolism*
  • Chromium / pharmacology*
  • Enzyme Activation / drug effects*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • Kidney / cytology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Reactive Oxygen Species / metabolism
  • Sphingomyelin Phosphodiesterase / metabolism*


  • Ceramides
  • Reactive Oxygen Species
  • Chromium
  • Sphingomyelin Phosphodiesterase