Psychosine is as potent an inducer of cell death as C6-ceramide in cultured fibroblasts and in MOCH-1 cells

Neurochem Res. 2001 Jun;26(6):667-71. doi: 10.1023/a:1010991420942.

Abstract

Cytotoxic capacity of psychosine (galactosylsphingosine) was evaluated in comparison with C6-ceramide in cultured fibroblasts and the glia-derived MOCH-1 cells that have characteristics of myelinating cells (1). Psychosine caused cytotoxic cell death and DNA fragmentation at concentrations similar to C6-ceramide and MOCH-1 cells were substantially more sensitive to their cytotoxic effects than fibroblasts. In this system, pretreatment with GM1-ganglioside failed to protect the cells from the deleterious effects of these compounds. These findings are consistent with the hypothesis that psychosine is the cytotoxic metabolite that causes apoptotic death of the oligodendrocyte in globoid cell leukodystrophy (Krabbe disease). They further suggest that the protective capacity of GM1-ganglioside is unlikely to be the explanation for the paradoxical improvement of the phenotype of globoid cell leukodystrophy in the mouse simultaneously deficient in two lysosomal beta-galactosidases, galactosylceramidase and GM1-ganglioside beta-galactosidase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Ceramides / antagonists & inhibitors
  • Ceramides / pharmacology*
  • DNA Fragmentation / drug effects
  • Fibroblasts / drug effects*
  • Fibroblasts / physiology*
  • G(M1) Ganglioside / pharmacology
  • Mice
  • Neuroglia / drug effects*
  • Neuroglia / physiology*
  • Psychosine / antagonists & inhibitors
  • Psychosine / pharmacology*
  • Tetrazolium Salts / pharmacology*

Substances

  • Ceramides
  • Tetrazolium Salts
  • N-caproylsphingosine
  • Psychosine
  • G(M1) Ganglioside