Genomes and Genes
Summary: Cholesterol which is substituted by a hydroxy group in any position.
- Rantham Prabhakara J, Feist G, Thomasson S, Thompson A, Schommer E, Ghribi O. Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on tyrosine hydroxylase and alpha-synuclein in human neuroblastoma SH-SY5Y cells. J Neurochem. 2008;107:1722-9 pubmed publisher..As steady state levels of 24-OHC and 27-OHC are tightly regulated in the brain, disturbances in these levels may contribute to the pathogenesis of PD. ..
- Ghribi O. Potential mechanisms linking cholesterol to Alzheimer's disease-like pathology in rabbit brain, hippocampal organotypic slices, and skeletal muscle. J Alzheimers Dis. 2008;15:673-84 pubmed..We also have found pathological hallmarks in the skeletal muscle of cholesterol-fed rabbits that are suggestive of inclusion body myositis, a disease that shares some pathological similarities with AD. ..
- Schule R, Siddique T, Deng H, Yang Y, Donkervoort S, Hansson M, et al. Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis. J Lipid Res. 2010;51:819-23 pubmed publisher..If the accumulation of 27-hydroxycholesterol is an important pathogenetic factor, a reduction of its levels may reduce or prevent the neurological symptoms. A possible strategy to achieve this is discussed. ..
- Xu L, Bai Q, Rodriguez Agudo D, Hylemon P, Heuman D, Pandak W, et al. Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate. Lipids. 2010;45:821-32 pubmed publisher..The current findings suggest that 25HC and 25HC3S serve as potent regulators in cross-talk of lipid metabolism and inflammatory response in the hepatocytes. ..
- Brown A, Jessup W. Oxysterols: Sources, cellular storage and metabolism, and new insights into their roles in cholesterol homeostasis. Mol Aspects Med. 2009;30:111-22 pubmed publisher..We summarise their location, generation, metabolism and elimination, as well as providing insights into the latest research into their regulatory roles in cholesterol homeostasis. ..
- Johnson J, Meliton V, Kim W, Lee K, Wang J, Nguyen K, et al. Novel oxysterols have pro-osteogenic and anti-adipogenic effects in vitro and induce spinal fusion in vivo. J Cell Biochem. 2011;112:1673-84 pubmed publisher..These data suggest that Oxy34 and Oxy49 are effective novel osteoinductive molecules and may be suitable candidates for further development and use in orthopedic indications requiring local bone formation. ..
- Marwarha G, Dasari B, Ghribi O. Endoplasmic reticulum stress-induced CHOP activation mediates the down-regulation of leptin in human neuroblastoma SH-SY5Y cells treated with the oxysterol 27-hydroxycholesterol. Cell Signal. 2012;24:484-92 pubmed publisher..Our study implicates ER stress as the mechanistic link in the 27-OHC-induced negative regulation of leptin, a hormone that has potential therapeutic effects in AD by reducing A? and phosphorylated tau accumulation. ..
- Fakheri R, Javitt N. 27-Hydroxycholesterol, does it exist? On the nomenclature and stereochemistry of 26-hydroxylated sterols. Steroids. 2012;77:575-7 pubmed publisher..Using this molecule as a starting point, this review hopes to establish a common language to keep all investigators on the same page. ..
- Gong Y, Lee J, Lee P, Goldstein J, Brown M, Ye J. Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake. Cell Metab. 2006;3:15-24 pubmed..When the new Insig-1 and cholesterol converge on Scap, Scap/SREBP binds to Insig-1, preventing ubiquitination. The Insig-1/Scap/SREBP complex accumulates in the ER, ready for liberation when the cell is again sterol deprived. ..
- Lutjohann D. Cholesterol metabolism in the brain: importance of 24S-hydroxylation. Acta Neurol Scand Suppl. 2006;185:33-42 pubmed..Within the last 10 years the interest in studying the mechanisms of this and other cholesterol transport systems has increased and the results from these in vivo and in vitro investigations are reviewed. ..
- Choi Y, Kim Y, Choi I, Kim S, Kim W. 25-hydroxycholesterol induces mitochondria-dependent apoptosis via activation of glycogen synthase kinase-3beta in PC12 cells. Free Radic Res. 2008;42:544-53 pubmed publisher..Pharmacological intervention of GSK-3beta-JNK-caspase signalling pathway may be useful for the reduction of cytotoxicity of oxysterols. ..
- Wang Y, Muneton S, Sjövall J, Jovanovic J, Griffiths W. The effect of 24S-hydroxycholesterol on cholesterol homeostasis in neurons: quantitative changes to the cortical neuron proteome. J Proteome Res. 2008;7:1606-14 pubmed publisher..Taken together, this data leads to the hypothesis that, in times of cholesterol excess, 24S-hydroxycholesterols signals down-regulation of cholesterol synthesis enzymes through SREBP-2, but up-regulates apo E synthesis (..
- Bjorkhem I. Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain. J Intern Med. 2006;260:493-508 pubmed..An overview of the above studies is presented and the possibility that the cholesterol 24S-hydroxylase in the brain may be important for memory and learning and that it may be a new drug target is discussed. ..
- Li X, Pandak W, Erickson S, Ma Y, Yin L, Hylemon P, et al. Biosynthesis of the regulatory oxysterol, 5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes. J Lipid Res. 2007;48:2587-96 pubmed..Specific small interfering RNA decreased SULT2B1b mRNA, protein, and activity levels. These findings demonstrate that mitochondria synthesize 25HC, which is subsequently 3beta-sulfated to form 25HC3S. ..
- Leoni V. Oxysterols as markers of neurological disease--a review. Scand J Clin Lab Invest. 2009;69:22-5 pubmed publisher..Compared with other available biomarkers in CSF, such as Total Tau, Phospo-Tau and beta(42) amyloid, the 24S-hydroxycholesterol appears to be the most sensitive biomarker in the evaluation of patients with cognitive impairment disease. ..
- Radhakrishnan A, Ikeda Y, Kwon H, Brown M, Goldstein J. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Proc Natl Acad Sci U S A. 2007;104:6511-8 pubmed..These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells. ..
- Palozza P, Simone R, Catalano A, Monego G, Barini A, Mele M, et al. Lycopene prevention of oxysterol-induced proinflammatory cytokine cascade in human macrophages: inhibition of NF-?B nuclear binding and increase in PPAR? expression. J Nutr Biochem. 2011;22:259-68 pubmed publisher..Taken all together, these data bring new information on the anti-atherogenic properties of lycopene, and on its mechanisms of action in atherosclerosis prevention. ..
- Morello F, Saglio E, Noghero A, Schiavone D, Williams T, Verhovez A, et al. LXR-activating oxysterols induce the expression of inflammatory markers in endothelial cells through LXR-independent mechanisms. Atherosclerosis. 2009;207:38-44 pubmed publisher..At proper dosage, synthetic LXR agonists are safe on endothelial cells and may even transrepress inflammatory reactions. ..
- Diczfalusy U, Olofsson K, Carlsson A, Gong M, Golenbock D, Rooyackers O, et al. Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide. J Lipid Res. 2009;50:2258-64 pubmed publisher..The possibility is discussed that 25-hydroxycholesterol may have a role in the inflammatory response, in addition to its more established role in the regulation of cholesterol homeostasis. ..
- Aghaloo T, Amantea C, Cowan C, Richardson J, Wu B, Parhami F, et al. Oxysterols enhance osteoblast differentiation in vitro and bone healing in vivo. J Orthop Res. 2007;25:1488-97 pubmed..These results identify oxysterols as potential agents in local and systemic enhancement of bone formation. ..
- Suchanek M, Hynynen R, Wohlfahrt G, Lehto M, Johansson M, Saarinen H, et al. The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket. Biochem J. 2007;405:473-80 pubmed..In addition, the ORP1L variant and ORP3, ORP5, and ORP8 were cross-linked with photoCH. The present study identifies ORP1 and ORP2 as OSBPs and suggests that most of the mammalian ORPs are able to bind sterols. ..
- Bai B, Yamamoto K, Sato H, Sugiura H, Tanaka T. Combined effect of 25-hydroxycholesterol and IL-1beta on IL-8 production in human colon carcinoma cell line (Caco-2). Inflammation. 2005;29:141-6 pubmed..These results suggest that 25-hydroxycholesterol enhances IL-1beta-induced IL-8 production, possibly by enhancing promoter activity. ..
- Joffre C, Leclère L, Buteau B, Martine L, Cabaret S, Malvitte L, et al. Oxysterols induced inflammation and oxidation in primary porcine retinal pigment epithelial cells. Curr Eye Res. 2007;32:271-80 pubmed..We conclude that in confluent primary porcine RPE cells, 24-hydroxycholesterol, 25-hydroxycholesterol, and 7-ketocholesterol are potent inducers of oxidation and inflammation. ..
- Ecker J, Liebisch G, Englmaier M, Grandl M, Robenek H, Schmitz G. Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes. Proc Natl Acad Sci U S A. 2010;107:7817-22 pubmed publisher..Therefore induction of fatty acid synthesis is a key requirement for phagocyte development and function. ..
- Bauman D, Bitmansour A, McDonald J, Thompson B, Liang G, Russell D. 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production. Proc Natl Acad Sci U S A. 2009;106:16764-9 pubmed publisher..The suppression of IgA class switching in B cells by a macrophage-derived sterol in response to TLR activation provides a mechanism for local and systemic negative regulation of the adaptive immune response by the innate immune system. ..
- Alkazemi D, Egeland G, Vaya J, Meltzer S, Kubow S. Oxysterol as a marker of atherogenic dyslipidemia in adolescence. J Clin Endocrinol Metab. 2008;93:4282-9 pubmed publisher..Serum oxysterol concentrations increase with obesity, insulin, and ApoB, which are established derangements associated with the metabolic syndrome. ..
- DeBarber A, Lutjohann D, Merkens L, Steiner R. Liquid chromatography-tandem mass spectrometry determination of plasma 24S-hydroxycholesterol with chromatographic separation of 25-hydroxycholesterol. Anal Biochem. 2008;381:151-3 pubmed publisher..The availability of an LC-MS method offers advantages such as simplified sample work-up and analysis. ..
- Yoshida Y, Kodai S, Takemura S, Minamiyama Y, Niki E. Simultaneous measurement of F2-isoprostane, hydroxyoctadecadienoic acid, hydroxyeicosatetraenoic acid, and hydroxycholesterols from physiological samples. Anal Biochem. 2008;379:105-15 pubmed publisher..t8-iso-PGF(2alpha), tHODE, tHETE, and t7-OHCh are measured satisfactorily and inclusively by the current method from biological fluids and tissues, and they can account for a large portion of oxidized lipids in vivo. ..
- Solomon A, Leoni V, Kivipelto M, Besga A, Oksengård A, Julin P, et al. Plasma levels of 24S-hydroxycholesterol reflect brain volumes in patients without objective cognitive impairment but not in those with Alzheimer's disease. Neurosci Lett. 2009;462:89-93 pubmed publisher..The findings on cholesterol agree with previous reports of decreasing plasma cholesterol levels in AD patients, suggesting a CNS-mediated effect on extracerebral cholesterol homeostasis. ..
- Javitt N. Oxysterols: functional significance in fetal development and the maintenance of normal retinal function. Curr Opin Lipidol. 2007;18:283-8 pubmed..This review shifts the focus of attention from studies of their ligand-binding activity to studies of animal models that indicate a number of important biologic effects during fetal development and during the aging process. ..
- Sharma I, Dhaliwal L, Saha S, Sangwan S, Dhawan V. Role of 8-iso-prostaglandin F2alpha and 25-hydroxycholesterol in the pathophysiology of endometriosis. Fertil Steril. 2010;94:63-70 pubmed publisher..To investigate the involvement of 8-iso-PGF(2alpha) and 25-hydroxycholesterol (25-OH-Chol) in the pathophysiology of endometriosis...
- Mitić T, Andrew R, Walker B, Hadoke P. 11?-Hydroxysteroid dehydrogenase type 1 contributes to the regulation of 7-oxysterol levels in the arterial wall through the inter-conversion of 7-ketocholesterol and 7?-hydroxycholesterol. Biochimie. 2013;95:548-55 pubmed publisher..This mechanism may be important in the cardioprotective effects of 11?-HSD1 inhibitors. ..
- Ren S, Li X, Rodriguez Agudo D, Gil G, Hylemon P, Pandak W. Sulfated oxysterol, 25HC3S, is a potent regulator of lipid metabolism in human hepatocytes. Biochem Biophys Res Commun. 2007;360:802-8 pubmed..In contrast, 25-hydroxycholesterol increased SREBP1 and FAS mRNA levels in primary human hepatocytes. The results imply that 25HC3S is a potent regulator of SREBP mediated lipid metabolism. ..
- Larsson H, Böttiger Y, Iuliano L, Diczfalusy U. In vivo interconversion of 7beta-hydroxycholesterol and 7-ketocholesterol, potential surrogate markers for oxidative stress. Free Radic Biol Med. 2007;43:695-701 pubmed..In addition, the biological within-day and between-day variations of the two oxysterols were determined. In summary, the present investigation clearly shows an interconversion of 7beta-hydroxycholesterol and 7-ketocholesterol in humans. ..
- Gale S, Westover E, Dudley N, Krishnan K, Merlin S, Scherrer D, et al. Side chain oxygenated cholesterol regulates cellular cholesterol homeostasis through direct sterol-membrane interactions. J Biol Chem. 2009;284:1755-64 pubmed publisher..These studies implicate oxysterol-membrane interactions in acute regulation of sterol homeostatic responses and provide new insights into the mechanism through which oxysterols regulate cellular cholesterol balance. ..
- Chen W, Chen G, Head D, Mangelsdorf D, Russell D. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab. 2007;5:73-9 pubmed..We conclude that oxysterols are in vivo ligands for LXR. ..
- Sharma S, Prasanthi R P J, Schommer E, Feist G, Ghribi O. Hypercholesterolemia-induced Abeta accumulation in rabbit brain is associated with alteration in IGF-1 signaling. Neurobiol Dis. 2008;32:426-32 pubmed publisher..We suggest that hypercholesterolemia-induced Abeta accumulation may be mediated by 27-hydroxycholesterol, involving IGF-1 signaling...
- Honda A, Miyazaki T, Ikegami T, Iwamoto J, Maeda T, Hirayama T, et al. Cholesterol 25-hydroxylation activity of CYP3A. J Lipid Res. 2011;52:1509-16 pubmed publisher..650, P < 0.0001, n = 78), but did not significantly correlate with the levels of 27-hydroxycholesterol or 24S-hydroxycholesterol. These results demonstrate the significance of CYP3A on the production of 25-hydroxycholesterol. ..
- Travert C, Carreau S, Le Goff D. Induction of apoptosis by 25-hydroxycholesterol in adult rat Leydig cells: protective effect of 17beta-estradiol. Reprod Toxicol. 2006;22:564-70 pubmed..These data suggested that this oxysterol can be used by rat Leydig cells in culture for sterol metabolism, but also induces apoptosis which could be inhibited by 17beta-estradiol. ..
- Nachtergaele S, Mydock L, Krishnan K, Rammohan J, Schlesinger P, Covey D, et al. Oxysterols are allosteric activators of the oncoprotein Smoothened. Nat Chem Biol. 2012;8:211-20 pubmed publisher..Our work suggests that these enigmatic sterols, which have multiple effects on cell physiology, may act as ligands for signaling receptors and provides a generally applicable framework for probing sterol signaling mechanisms. ..
- Riendeau V, Garenc C. Effect of 27-hydroxycholesterol on survival and death of human macrophages and vascular smooth muscle cells. Free Radic Res. 2009;43:1019-28 pubmed publisher..All together, cell survival triggered by LXRs is impaired in the presence of cholesterol or high concentrations of 27-OH in human U937 macrophages and is not effective in HASMC. ..
- Vejux A, Lizard G. Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis. Mol Aspects Med. 2009;30:153-70 pubmed publisher..This basic knowledge on oxysterols contributes to a better understanding of the associated pathologies, so that new treatments and drugs can be designed. ..
- Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira J, et al. Oxysterols direct immune cell migration via EBI2. Nature. 2011;475:524-7 pubmed publisher..This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response. ..
- Ma Y, Xu L, Rodriguez Agudo D, Li X, Heuman D, Hylemon P, et al. 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol Endocrinol Metab. 2008;295:E1369-79 pubmed publisher..We conclude that 25HC3S acts in macrophages as a cholesterol satiety signal, downregulating cholesterol and fatty acid synthetic pathways via inhibition of LXR/SREBP signaling. A possible role of oxysterol sulfation is proposed. ..