Fluorescent analogues of plasma membrane sphingolipids are sorted to different intracellular compartments in astrocytes: Harmful effects of chronic ethanol exposure on sphingolipid trafficking and metabolism

Mónica Tomás, Juan M. Durán, Francisco Lázaro-Diéguez, Teresa Babià, Jaime Renau-Piqueras, Gustavo Egea

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Sphingolipids are basic constituents of cellular membranes and are essential for numerous functions such as intracellular signalling. They are transported along the exocytic and endocytic pathways in eukaryotic cells. After endocytosis, fluorescent-labelled sphingolipids are sorted to distinct intracellular organelles prior to recycling (via early/recycling endosomes) or degradation (late endosomes/lysosomes). Here we examine, in primary cultures of rat astrocytes, the internalisation routes followed by C6-NBD- glucosylceramide (NBD-GlcCer) and C6-NBD-sphingomyelin (NBD-SM) and the effects of ethanol on their endocytic trafficking. Endocytosed plasma membrane NBD-GlcCer and NBD-SM are diverted to the Golgi apparatus and lysosomes, respectively. These different internalisation pathways are maintained regardless of the differentiation stage of astrocytes. Chronic ethanol exposure did not alter this endocytic sorting, but delayed the internalisation of both NBD-sphingolipids. Moreover, ethanol also stimulated the in situ metabolism of NBD-ceramide to NBD-GlcCer and NBD-SM. We conclude that in rat astrocytes internalised plasma membrane NBD-sphingolipids are sorted to different subcellular compartments. The exposure to chronic ethanol perturbed the lipid endocytic process and stimulated the de novo synthesis of NBD-sphingolipids, shifting the balance of sphingolipid metabolism in favour of the sphingomyelin pathway.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalFEBS Letters
Volume563
Issue number1-3
DOIs
StatePublished - Apr 9 2004

Keywords

  • Alcohol
  • Endocytosis
  • Endosome
  • Glial cell
  • Golgi apparatus
  • NBD-lipid

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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