566-26-7Relevant articles and documents
Additional pathways of sterol metabolism: Evidence from analysis of Cyp27a1?/? mouse brain and plasma
Griffiths, William J.,Crick, Peter J.,Meljon, Anna,Theofilopoulos, Spyridon,Abdel-Khalik, Jonas,Yutuc, Eylan,Parker, Josie E.,Kelly, Diane E.,Kelly, Steven L.,Arenas, Ernest,Wang, Yuqin
, p. 191 - 211 (2019/01/03)
Cytochrome P450 (CYP) 27A1 is a key enzyme in both the acidic and neutral pathways of bile acid biosynthesis accepting cholesterol and ring-hydroxylated sterols as substrates introducing a (25R)26-hydroxy and ultimately a (25R)26-acid group to the sterol side-chain. In human, mutations in the CYP27A1 gene are the cause of the autosomal recessive disease cerebrotendinous xanthomatosis (CTX). Surprisingly, Cyp27a1 knockout mice (Cyp27a1?/?) do not present a CTX phenotype despite generating a similar global pattern of sterols. Using liquid chromatography – mass spectrometry and exploiting a charge-tagging approach for oxysterol analysis we identified over 50 cholesterol metabolites and precursors in the brain and circulation of Cyp27a1?/? mice. Notably, we identified (25R)26,7α- and (25S)26,7α-dihydroxy epimers of oxysterols and cholestenoic acids, indicating the presence of an additional sterol 26-hydroxylase in mouse. Importantly, our analysis also revealed elevated levels of 7α-hydroxycholest-4-en-3-one, which we found increased the number of oculomotor neurons in primary mouse brain cultures. 7α-Hydroxycholest-4-en-3-one is a ligand for the pregnane X receptor (PXR), activation of which is known to up-regulate the expression of CYP3A11, which we confirm has sterol 26-hydroxylase activity. This can explain the formation of (25R)26,7α- and (25S)26,7α-dihydroxy epimers of oxysterols and cholestenoic acids; the acid with the former stereochemistry is a liver X receptor (LXR) ligand that increases the number of oculomotor neurons in primary brain cultures. We hereby suggest that a lack of a motor neuron phenotype in some CTX patients and Cyp27a1?/? mice may involve increased levels of 7α-hydroxycholest-4-en-3-one and activation PXR, as well as increased levels of sterol 26-hydroxylase and the production of neuroprotective sterols capable of activating LXR.
Effect of Eleven Antioxidants in Inhibiting Thermal Oxidation of Cholesterol
Xu, Guihua,Liu, Donghong,Zhao, Gongling,Chen, Shiguo,Wang, Jun,Ye, Xingqian
, p. 215 - 225 (2016/02/03)
Eleven antioxidants including nine phenolic compounds (rutin, quercetin, hesperidin, hesperetin, naringin, naringenin, chlorogenic acid, caffeic acid, ferulic acid), vitamin E (α-tocopherol), and butylated hydroxytoluene (BHT) were selected to investigate their inhibitory effects on thermal oxidation of cholesterol in air and lard. The results indicated that the unoxidized cholesterol decreased with heating time whilst cholesterol oxidation products (COPs) increased with heating time. The major COPs produced were 7α-hydroxycholesterol, 7β-hydroxycholesterol, 5,6β-epoxycholesterol, 5,6α-epoxycholesterol, and 7-ketocholesterol. When cholesterol was heated in air for an hour, rutin, quercetin, chlorogenic acid, and caffeic acid showed a strong inhibitory effect. When cholesterol was heated in lard, caffeic acid, quercetin, and chlorogenic acid demonstrated inhibitory action during the initial 0.5 h (p a high flame is recommended. If baking or deep fat frying food in oil, it is best to limit cooking time to within 0.5 h.
Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4α- and 4β-hydroxycholesterol) and C7 (7-ketocholesterol, 7α- and 7β-hydroxycholesterol) on cells of the central nervous system
Nury, Thomas,Samadi, Mohammad,Zarrouk, Amira,Riedinger, Jean Marc,Lizard, Gérard
, p. 558 - 567 (2013/12/04)
Whereas the biological activities of oxysterols oxidized at C7 (7-ketocholesterol (7KC), 7β-hydroxycholesterol (7β-OHC), 7α-hydroxycholesterol (7α-OHC)) are well documented, those of oxysterols oxidized at C4 (4β-hydroxycholesterol (4β-OHC), 4α-hydroxycholesterol (4α-OHC)) are not well known, especially on the cells of the central nervous system. Therefore, an improved methodology has been validated for 4β-OHC and 4α-OHC synthesis, and the effects on cell viability and cell growth of these molecules were studied on immortalized, tumoral and normal brain cells (158N, C6 and SK-N-BE cells, and mixed primary cultures of astrocytes and oligodendrocytes). Whereas inhibition of cell growth with 7KC, 7β-OHC, and 7α-OHC is associated with a decrease of cell viability (cytotoxic activities), our data establish that 4β-OHC and 4α-OHC have no effect on cell viability, and no or minor effect on cell growth evocating cytostatic properties. Thus, comparatively to oxysterols oxidized at C7, the toxicity of oxysterols oxidized at C4 is in the following range of order: 7KC ≥ 7β-OHC > 7α-OHC > (4β-OHC ≥ 4α-OHC). Interestingly, to date, 4β-OHC and 4α-OHC are the only oxysterols identified with cytostatic properties suggesting that these molecules, whereas not cytotoxic, may have some interests to counteract cell proliferation.
