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malfunction
mice with a disruption in the cholesterol 25-hydroxylase gene regulate cholesterol metabolism normally. Ch25h-/- mice have higher levels of mRNAs coding for immunoglobulin A and immunoglobulin J. Disruption in the Cyp7b1 gene leads to significantly increased levels of 25-hydroxycholesterol in the circulation, and to significantly lower levels of IgA compared to wild-type mice
physiological function
important role for 25-hydroxycholesterol in the immune system. High concentrations of 25-hydroxycholesterol induce apoptosis in a mouse oligodendrocyte cell line 158N in an liver X receptor-independent manner. Treatment of these cells with 25-hydroxycholesterol results in enhanced secreted phospholipase A2 activity
malfunction
loss of function of Ch25h leads to susceptibility to viral infections in vitro
physiological function
cholesterol 25-hydroxylase plays an essential role in cholesterol metabolism in the body by catalysing the formation of 25-hydroxycholesterol from cholesterol which acts to repress cholesterol biosynthesis
physiological function
cholesterol-25-hydroxylase acts as a broadly antiviral interferon-stimulated gene. CH25H converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol. 25-Hydroxycholesterol treatment in cultured cells broadly inhibits growth of enveloped viruses including VSV, HSV, HIV, and MHV68 and acutely pathogenic EBOV, RVFV, RSSEV, and Nipah viruses. The compound inhibits cell entry of viruses HIV and VSV, and inhibits viral protein-mediated cell-cell membrane fusion of virus NIV. 25-Hydroxycholesterol directly modifies membranes
physiological function
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adenovirus-mediated enzyme overexpression in mice improves glucose tolerance and insulin sensitivity and lowers the homeostatic model assessment for insulin resistance score
additional information
25-hydroxycholesterol does not stimulate the sPLA2-IIA promoter in the mouse Schwann cell line MSC80
additional information
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Ch25h expression is controlled primarily by type I IFN signaling, type1 IFN-mediated Ch25h expression is IFNR-dependent, overview
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Russell, D.W.
Oxysterol biosynthetic enzymes
Biochim. Biophys. Acta
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126-135
2000
Homo sapiens (O95992), Mus musculus (Q9Z0F5)
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Lund, E.G.; Kerr, T.A.; Sakai, J.; Li, W.P.; Russell, D.W.
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1998
Homo sapiens (O95992), Mus musculus (Q9Z0F5)
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Diczfalusy, U.; Olofsson, K.; Carlsson, A.; Gong, M.; Golenbock, D.; Rooyackers, O.; Flring, U.; Bjrkbacka, H.
Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide
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Homo sapiens, Mus musculus
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Bauman, D.R.; Bitmansour, A.D.; McDonald, J.G.; Thompson, B.M.; Liang, G.; Russell, D.W.
25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production
Proc. Natl. Acad. Sci. USA
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16764-16769
2009
Mus musculus
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Park, K.; Scott, A.L.
Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons
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2010
Mus musculus, Mus musculus BALB/cJ
brenda
Holmes, R.S.; Vandeberg, J.L.; Cox, L.A.
Genomics and proteomics of vertebrate cholesterol ester lipase (LIPA) and cholesterol 25-hydroxylase (CH25H)
3 Biotech
1
99-109
2011
Bos taurus (Q0P599), Canis lupus familiaris, Equus caballus (F6T000), Gallus gallus, Homo sapiens (O95992), Homo sapiens, Macaca mulatta (F7EC50), Mus musculus (Q9Z0F5), Rattus norvegicus (Q4QQV7), Xenopus tropicalis
brenda
Diczfalusy, U.
On the formation and possible biological role of 25-hydroxycholesterol
Biochimie
95
455-460
2013
Rattus norvegicus, Sus scrofa, Homo sapiens (Q02318), Mus musculus (Q64459)
brenda
Liu, S.Y.; Aliyari, R.; Chikere, K.; Li, G.; Marsden, M.D.; Smith, J.K.; Pernet, O.; Guo, H.; Nusbaum, R.; Zack, J.A.; Freiberg, A.N.; Su, L.; Lee, B.; Cheng, G.
Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol
Immunity
38
92-105
2013
Mus musculus (Q9Z0F5)
brenda
Honda, A.; Miyazaki, T.; Ikegami, T.; Iwamoto, J.; Maeda, T.; Hirayama, T.; Saito, Y.; Teramoto, T.; Matsuzaki, Y.
Cholesterol 25-hydroxylation activity of CYP3A
J. Lipid Res.
52
1509-1516
2011
Homo sapiens (P05177), Homo sapiens (P08684), Homo sapiens (P10635), Homo sapiens (P11712), Mus musculus (Q9Z0F5)
brenda
Li, Z.; Martin, M.; Zhang, J.; Huang, H.Y.; Bai, L.; Zhang, J.; Kang, J.; He, M.; Li, J.; Maurya, M.R.; Gupta, S.; Zhou, G.; Sangwung, P.; Xu, Y.J.; Lei, T.; Huang, H.D.; Jain, M.; Jain, M.K.; Subramaniam, S.; Shyy, J.Y.
Krueppel-like factor 4 regulation of cholesterol-25-hydroxylase and liver X receptor mitigates atherosclerosis susceptibility
Circulation
136
1315-1330
2017
Mus musculus (Q9Z0F5)
brenda
Noebauer, B.; Jais, A.; Todoric, J.; Gossens, K.; Sutterluety-Fall, H.; Einwallner, E.
Hepatic cholesterol-25-hydroxylase overexpression improves systemic insulin sensitivity in mice
J. Diabetes Res.
2017
4108768
2017
Mus musculus
brenda
Mukherjee, P.; Hough, G.; Chattopadhyay, A.; Navab, M.; Fogelman, H.R.; Meriwether, D.; Williams, K.; Bensinger, S.; Moller, T.; Faull, K.F.; Lusis, A.J.; Iruela-Arispe, M.L.; Bostrom, K.I.; Tontonoz, P.; Reddy, S.T.; Fogelman, A.M.
Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-beta and cholesterol 25-hydroxylase in jejunum
J. Lipid Res.
58
1636-1647
2017
Mus musculus
brenda