The cross roles of sphingosine kinase 1/2 and ceramide glucosyltransferase in cell growth and death

Biochem Biophys Res Commun. 2018 Jun 7;500(3):597-602. doi: 10.1016/j.bbrc.2018.04.110. Epub 2018 Apr 23.

Abstract

Sphingosine-1-phosphate is synthesized by two sphingosine kinases, cytosolic SK1 and nuclear SK2 but SK2 expression was much higher than SK1in mouse skin fibroblasts. However, in SK2-/- cells, SK1 expression was markedly increased to SK2 levels whereas in SK1-/- cells, SK2 expression was unaffected. Ceramide, glucosylceramide and sphingosine levels were all increased in SK1-/- but less so in SK2-/- cells and S1P levels were not significantly reduced in either SK1-/- or SK2-/- cells. Greatly increased Ceramide glucosyltransferase expression was observed in SK1-/- cells but less so in SK2-/- cells suggested a role in drug resistance. SK2-/- cells grew faster than control and SK1-/-. The cell division gene PCNA was significantly overexpressed in SK2-/- cells, suggesting a cross regulation between SKs and Ceramide glucosyltransferase.

Keywords: Anti-cancer; Cell cycle; Ceramide; Ceramide glucosyltransferase; S1P; Sphingosine; Sphingosine kinases 1 and 2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Death
  • Cell Line
  • Cell Proliferation
  • Chromatography, High Pressure Liquid
  • Fibroblasts / cytology*
  • Fibroblasts / enzymology*
  • Glucosylceramides / metabolism
  • Glucosyltransferases / metabolism*
  • Mice
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Skin / cytology
  • Sphingolipids / metabolism
  • Tandem Mass Spectrometry

Substances

  • Glucosylceramides
  • Sphingolipids
  • Glucosyltransferases
  • ceramide glucosyltransferase
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase