Diverse functions of 24(S)-hydroxycholesterol in the brain

Noriko Noguchi, Yoshiro Saito, Yasuomi Urano

Research output: Contribution to journalReview articlepeer-review

39 Citations (Scopus)

Abstract

24(S)-hydroxycholesterol (24S-OHC) which is enzymatically produced in the brain plays important physiological roles in maintaining brain cholesterol homeostasis. We found that 24S-OHC at sub-lethal concentrations down-regulated amyloid precursor protein (APP) trafficking via enhancement of the complex formation of APP with up-regulated glucose-regulated protein 78, an endoplasmic reticulum chaperone. In accordance with this mechanism, 24S-OHC suppressed amyloid-β production in human neuroblastoma SH-SY5Y cells. Furthermore, 24S-OHC at sub-lethal concentrations induced adaptive responses via transcriptional activation of the liver X receptor signaling pathway, thereby protecting neuronal cells against the forthcoming oxidative stress induced by 7-ketocholesterol. On the other hand, we found that high concentrations of 24S-OHC induced apoptosis in T-lymphoma Jurkat cells which endogenously expressed caspase-8, and induced necroptosis - a form of programmed necrosis - in neuronal SH-SY5Y cells which expressed no caspase-8. In this Article, we show the diverse functions of 24S-OHC and consider the possible importance of controlling 24S-OHC levels in the brain for preventing neurodegenerative diseases.

Original languageEnglish
Pages (from-to)692-696
Number of pages5
JournalBiochemical and biophysical research communications
Volume446
Issue number3
DOIs
Publication statusPublished - 2014 Apr 11
Externally publishedYes

Keywords

  • 24(S)-hydroxycholesterol
  • 7-Ketocholesterol
  • Adaptive response
  • Necroptosis
  • Neurodegenerative disease

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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