SRIEBP-1c expression in Schwann cells is affected by diabetes and nutritional status

Anne-Sophie de Preux, Katinka Goosen, Weixian Zhang, Anders A. F. Sima, Hitoshi Shimano, D. Margriet Ouwens, Michaela Diamant, Jan-Luuk Hillebrands, Jan Rozing, Greg Lemke, Jacques S. Beckmann, August B. Smit, Mark H. G. Verheijen*, Roman Chrast

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Our previous work demonstrated that the sterol response element binding proteins (SREBP)-1 and SREBP-2, which are the key regulators of storage lipid and cholesterol metabolism respectively, are highly expressed in Schwann cells of adult peripheral nerves. In order to evaluate the role of Schwann cell SREBPs in myelination and functioning of peripheral nerves we have determined their expression during development, after fasting and refeeding, and in a rodent model of diabetes. Our results show that SREBP-le and SREBP-2, unlike SREBP-la, are the major forms of SREBPs present in peripheral nerves. The expression profile of SREBP-2 follows the expression of genes involved in cholesterol biosynthesis, while SREBP-1c is co-expressed with genes involved in storage lipid metabolism. In addition, the expression of SREBP-1c in the endoneurial compartment of peripheral nerves depends on nutritional status and is disturbed in type I diabetes. In line with this, insulin elevates the expression of SREBP-1c in primary cultured Schwann cells by activating the SREBP-le promoter. Taken together, these findings reveal that SREBP-1c expression in Schwann cells responds to metabolic stimuli including insulin and that this response is affected in type I diabetes mellitus. This suggests that disturbed SREBP-1c regulated lipid metabolism may contribute to the pathophysiology of diabetic peripheral neuropathy. (c) 2007 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)525-534
Number of pages10
JournalMolecular and Cellular Neuroscience
Volume35
Issue number4
DOIs
Publication statusPublished - Aug-2007

Keywords

  • Schwann cell
  • diabetic peripheral neuropathy
  • lipid metabolism
  • ELEMENT-BINDING PROTEIN-1C
  • AXO-GLIAL DYSJUNCTION
  • ESSENTIAL FATTY-ACIDS
  • GAMMA-LINOLENIC ACID
  • BIO-BREEDING RAT
  • GENE-EXPRESSION
  • PERIPHERAL-NERVE
  • C-PEPTIDE
  • CULTURED-CELLS
  • NEUROPATHY

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