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22R-Hydroxycholesterol induces differentiation of human NT2 precursor (Ntera2/D1 teratocarcinoma) cells.

Abstract
Recently, we have shown that 22R-hydroxycholesterol, a steroid intermediate in the pathway of pregnenolone formation from cholesterol, is present at lower levels in Alzheimer's disease (AD) hippocampus and frontal cortex tissue specimens than in age-matched controls, and that this substance protects against cell death induced by amyloid beta-peptide in both rat sympathetic nerve pheochromocytoma (PC12) and differentiated human Ntera2/D1 teratocarcinoma neurons. Herein we report that 22R-hydroxycholesterol inhibits the proliferation of human Ntera2/D1 teratocarcinoma precursor cells (NT2) and induces these cells to differentiate into "neuron-like" or "astrocyte-like" cells. 22R-Hydroxycholesterol-induced differentiation of NT2 cells is associated with increases in the expression of neurofilament protein NF200, the cytoskeletal proteins microtubule-associated protein type II (MAP2) a and MAP2b, glial fibrillary acidic protein (GFAP) and glial cell line-derived neurotrophic factor receptor-alpha 2 (GFRalpha2). These effects of 22R-hydroxycholesterol are considered to be stereospecific because its enantiomer 22S-hydroxycholesterol and other steroids failed to induce differentiation of NT2 cells. 22R-Hydroxycholesterol was found to lack specific binding for numerous receptors, including all steroid receptors tested. However, using a cholesterol protein binding blot assay we demonstrated the presence of a 22R-hydroxycholesterol-binding protein in NT2 cells distinct from the human oxysterol receptors liver X receptor LXRalpha and beta.
AuthorsZ-X Yao, Z Han, J Xu, J Greeson, L Lecanu, V Papadopoulos
JournalNeuroscience (Neuroscience) Vol. 148 Issue 2 Pg. 441-53 (Aug 24 2007) ISSN: 0306-4522 [Print] United States
PMID17689017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • GFR protein, human
  • Guanine Nucleotide Exchange Factors
  • Hydroxycholesterols
  • Nerve Tissue Proteins
  • Tetrazolium Salts
  • Thiazoles
  • Tritium
  • 22-hydroxycholesterol
  • thiazolyl blue
  • Cholesterol
  • L-Lactate Dehydrogenase
  • Bromodeoxyuridine
Topics
  • Bromodeoxyuridine
  • Cell Death (drug effects)
  • Cell Differentiation (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cholesterol (metabolism, pharmacology)
  • Dose-Response Relationship, Drug
  • Flow Cytometry (methods)
  • Gene Expression Regulation (drug effects)
  • Guanine Nucleotide Exchange Factors (metabolism)
  • Humans
  • Hydroxycholesterols (metabolism, pharmacology)
  • L-Lactate Dehydrogenase
  • Nerve Tissue Proteins (metabolism)
  • Neurons (drug effects, physiology)
  • Teratocarcinoma
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors
  • Tritium (metabolism)

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