High glucose upregulates CYP24A1 expression which attenuates the ability of 1,25(OH)2D3 to increase NGF secretion in a rat Schwann cell line RSC96

Mol Cell Endocrinol. 2015 Mar 15:404:75-81. doi: 10.1016/j.mce.2015.01.005. Epub 2015 Jan 20.

Abstract

Vitamin D deficiency or insufficiency is an independent risk factor for diabetic peripheral neuropathy (DPN), but the relationship between 1,25(OH)2D3 and DPN remains unknown. We found that 1,25(OH)2D3 stimulated the secretion of nerve growth factor (NGF) in rat Schwann cell line RSC96, but ability of 1,25(OH)2D3 to increase NGF protein was impaired under high glucose conditions. High glucose upregulated the expression of CYP24A1 protein, which catalyzes the conversion of 1,25(OH)2D3 into inactive products, further impairing the ability of 1,25(OH)2D3 to upregulate NGF secretion in Schwann cells. Inhibition of CYP24A1 protein expression ameliorated the secretion of NGF in response to 1,25(OH)2D3. The findings of this study suggest that CYP24A1 protein plays an important role in the relationship between DPN and 1,25(OH)2D3.

Keywords: 1,25(OH)(2)D(3); CYP24A1; High glucose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitriol / pharmacokinetics*
  • Calcitriol / pharmacology
  • Cell Line
  • Cell Proliferation / drug effects
  • Diabetic Neuropathies / enzymology
  • Genistein / pharmacology
  • Glucose / pharmacology*
  • Nerve Growth Factor / metabolism*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Schwann Cells / cytology
  • Schwann Cells / drug effects
  • Schwann Cells / enzymology*
  • Up-Regulation
  • Vitamin D3 24-Hydroxylase / metabolism*

Substances

  • Reactive Oxygen Species
  • Nerve Growth Factor
  • Genistein
  • Cyp24a1 protein, rat
  • Vitamin D3 24-Hydroxylase
  • Calcitriol
  • Glucose