TY - JOUR
T1 - Diverse functions of 24(S)-hydroxycholesterol in the brain
AU - Noguchi, Noriko
AU - Saito, Yoshiro
AU - Urano, Yasuomi
N1 - Funding Information:
This work was supported in part by JSPS KAKENHI Grant-in-Aid for Young Scientists (B) 23700428, 25830041 to Y.U. and the Takeda Science Foundation to Y.U. and the MEXT-Supported Program for the Strategic Research Foundation at Private Universities in Japan for the years 2012–2016.
PY - 2014/4/11
Y1 - 2014/4/11
N2 - 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.
AB - 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.
KW - 24(S)-hydroxycholesterol
KW - 7-Ketocholesterol
KW - Adaptive response
KW - Necroptosis
KW - Neurodegenerative disease
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UR - http://www.scopus.com/inward/citedby.url?scp=84898825097&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2014.02.010
DO - 10.1016/j.bbrc.2014.02.010
M3 - Review article
C2 - 24530911
AN - SCOPUS:84898825097
SN - 0006-291X
VL - 446
SP - 692
EP - 696
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
