Genomes and Genes
Summary: Cholesterol substituted in any position by a keto moiety. The 7-keto isomer inhibits cholesterol uptake in the coronary arteries and aorta by blocking 3-hydroxy-3-methylglutaryl-CoA reductase activity.
- Kahn E, Baarine M, Dauphin A, Ragot K, Tissot N, Seguin A, et al. Impact of 7-ketocholesterol and very long chain fatty acids on oligodendrocyte lipid membrane organization: evaluation via LAURDAN and FAMIS spectral image analysis. Cytometry A. 2011;79:293-305 pubmed publisher..Only 7KC was capable to induce a green emission with LAURDAN. Thus, at concentrations inducing oligodendrocyte cell death, 7KC (25 ?M) is more efficient than C24:0 and C26:0 (20 ?M), to trigger lateral lipid membrane disorganization. ..
- Ferderbar S, Pereira E, Apolinario E, Bertolami M, Faludi A, Monte O, et al. Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus. Diabetes Metab Res Rev. 2007;23:35-42 pubmed..ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients. ..
- Odermatt A, Atanasov A, Balazs Z, Schweizer R, Nashev L, Schuster D, et al. Why is 11beta-hydroxysteroid dehydrogenase type 1 facing the endoplasmic reticulum lumen? Physiological relevance of the membrane topology of 11beta-HSD1. Mol Cell Endocrinol. 2006;248:15-23 pubmed..These aspects may be relevant for understanding the physiological role of 11beta-HSD1 and for developing therapeutic interventions to control glucocorticoid reactivation. ..
- Wamil M, Andrew R, Chapman K, Street J, Morton N, Seckl J. 7-oxysterols modulate glucocorticoid activity in adipocytes through competition for 11beta-hydroxysteroid dehydrogenase type. Endocrinology. 2008;149:5909-18 pubmed publisher..Thus, the activity and reaction direction of adipose 11beta-HSD1 is altered under conditions of oxysterol excess, and could impact upon the pathophysiology of obesity and its complications. ..
- Martinet W, Schrijvers D, Timmermans J, Bult H. Interactions between cell death induced by statins and 7-ketocholesterol in rabbit aorta smooth muscle cells. Br J Pharmacol. 2008;154:1236-46 pubmed publisher..This further illustrates that drug effects in normal SMCs are not necessarily predictive for activities in atherosclerotic settings. ..
- Endo K, Oyama T, Saiki A, Ban N, Ohira M, Koide N, et al. Determination of serum 7-ketocholesterol concentrations and their relationships with coronary multiple risks in diabetes mellitus. Diabetes Res Clin Pract. 2008;80:63-8 pubmed publisher..3+/-7.0 ng/ml). Furthermore, s-7KCHO increased according to the number of concurrent coronary risk factors. These results suggest that serum 7-ketocholesterol levels may depend on the multiple risk factors and serum LDL-C levels. ..
- Steffen Y, Wiswedel I, Peter D, Schewe T, Sies H. Cytotoxicity of myeloperoxidase/nitrite-oxidized low-density lipoprotein toward endothelial cells is due to a high 7beta-hydroxycholesterol to 7-ketocholesterol ratio. Free Radic Biol Med. 2006;41:1139-50 pubmed..The dietary polyphenol (-)-epicatechin inhibited not only formation but also cytotoxic actions of both oxLDL and oxysterols. ..
- Lizard G, Gueldry S, Sordet O, Monier S, Athias A, Miguet C, et al. Glutathione is implied in the control of 7-ketocholesterol-induced apoptosis, which is associated with radical oxygen species production. FASEB J. 1998;12:1651-63 pubmed..Taken together, our data demonstrate that GSH is implied in the control of 7-ketocholesterol-induced apoptosis associated with the production of ROS. ..
- Schweizer R, Z rcher M, Balazs Z, Dick B, Odermatt A. Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, and hamster enzyme. J Biol Chem. 2004;279:18415-24 pubmed publisher..Together, our results suggest that 11beta-HSD1 efficiently catalyzes the first step in the rapid hepatic metabolism of dietary 7KC, which may explain why dietary 7KC has little or no effect on the development of atherosclerosis...
- Deckert V, Duverneuil L, Poupon S, Monier S, Le Guern N, Lizard G, et al. The impairment of endothelium-dependent arterial relaxation by 7-ketocholesterol is associated with an early activation of protein kinase C. Br J Pharmacol. 2002;137:655-62 pubmed
- Rodriguez I, Alam S, Lee J. Cytotoxicity of oxidized low-density lipoprotein in cultured RPE cells is dependent on the formation of 7-ketocholesterol. Invest Ophthalmol Vis Sci. 2004;45:2830-7 pubmed..The formation of 7KCh seems to be responsible for most of the cytotoxicity associated with oxLDL internalization in ARPE19 cells. ..
- Huang J, Amaral J, Lee J, Larrayoz I, Rodriguez I. Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization. Biochim Biophys Acta. 2012;1821:637-46 pubmed publisher..Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration...
- Ostroumova O, Kaulin Y, Gurnev P, Schagina L. Effect of agents modifying the membrane dipole potential on properties of syringomycin E channels. Langmuir. 2007;23:6889-92 pubmed..Overall, the results support the model of the small SRE channel synchronization in the cluster as voltage-dependent orientation of the lipid dipoles associated with the channel pores. ..
- Balazs Z, Nashev L, Chandsawangbhuwana C, Baker M, Odermatt A. Hexose-6-phosphate dehydrogenase modulates the effect of inhibitors and alternative substrates of 11beta-hydroxysteroid dehydrogenase 1. Mol Cell Endocrinol. 2009;301:117-22 pubmed publisher..In conclusion, cellular factors such as H6PDH can significantly modulate the effect of inhibitors and alternative 7-oxygenated substrates on intracellular glucocorticoid availability. ..
- Kiss L, Chen M, Gero D, Módis K, Lacza Z, Szabo C. Effects of 7-ketocholesterol on the activity of endothelial poly(ADP-ribose) polymerase and on endothelium-dependent relaxant function. Int J Mol Med. 2006;18:1113-7 pubmed..Our experimental results suggest that although 7-ketocholesterol can activate PARP enzyme in endothelial cells, it is not sufficient on its own to cause impairment in the endothelium-dependent vascular reactivity. ..
- Li X, Momsen M, Brockman H, Brown R. Sterol structure and sphingomyelin acyl chain length modulate lateral packing elasticity and detergent solubility in model membranes. Biophys J. 2003;85:3788-801 pubmed
- Hitsumoto T, Takahashi M, Iizuka T, Shirai K. Clinical significance of serum 7-ketocholesterol concentrations in the progression of coronary atherosclerosis. J Atheroscler Thromb. 2009;16:363-70 pubmed..01, <0.05, <0.05, respectively). These results indicate that high s-7KCHO is closely associated with the progression of coronary atherosclerosis and inflammation. ..
- 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. ..
- Vejux A, Lizard G, Tourneur Y, Riedinger J, Frouin F, Kahn E. Effects of caspase inhibitors (z-VAD-fmk, z-VDVAD-fmk) on Nile Red fluorescence pattern in 7-ketocholesterol-treated cells: investigation by flow cytometry and spectral imaging microscopy. Cytometry A. 2007;71:550-62 pubmed..They also favor the hypothesis of relationships between caspase activity and polar lipid accumulation. ..
- Seye C, Knaapen M, Daret D, Desgranges C, Herman A, Kockx M, et al. 7-Ketocholesterol induces reversible cytochrome c release in smooth muscle cells in absence of mitochondrial swelling. Cardiovasc Res. 2004;64:144-53 pubmed..The reversibility of these events suggests that the apoptotic cascade could be arrested before a point of no return. ..
- Berthier A, Lemaire Ewing S, Prunet C, Montange T, Vejux A, Pais de Barros J, et al. 7-Ketocholesterol-induced apoptosis. Involvement of several pro-apoptotic but also anti-apoptotic calcium-dependent transduction pathways. FEBS J. 2005;272:3093-104 pubmed..Therefore, it appears that 7-ketocholesterol-induced apoptosis is a complex phenomenon resulting from calcium-dependent activation of several pro-apoptotic pathways and also one survival pathway. ..
- Rodriguez I, Larrayoz I. Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration. J Lipid Res. 2010;51:2847-62 pubmed publisher..The chronic mode of formation and the potent inflammatory properties of 7KCh indicate it may be an "age-related" risk factor in aging diseases such as atherosclerosis, Alzheimer's, and age-related macular degeneration. ..
- Cladera J, O Shea P, Hadgraft J, Valenta C. Influence of molecular dipoles on human skin permeability: Use of 6-ketocholestanol to enhance the transdermal delivery of bacitracin. J Pharm Sci. 2003;92:1018-27 pubmed
- 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. ..
- Vejux A, Guyot S, Montange T, Riedinger J, Kahn E, Lizard G. Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosis. J Nutr Biochem. 2009;20:45-61 pubmed publisher..Thus, 7KC-induced apoptosis is a PI3-K-dependent event, and Vit-E up- and down-regulates PI3-K activity and phospholipidosis, respectively. ..
- Smondyrev A, Berkowitz M. Effects of oxygenated sterol on phospholipid bilayer properties: a molecular dynamics simulation. Chem Phys Lipids. 2001;112:31-9 pubmed..Results of our simulations are in a good agreement with the data available from the experiment. ..
- Jessup W, Wilson P, Gaus K, Kritharides L. Oxidized lipoproteins and macrophages. Vascul Pharmacol. 2002;38:239-48 pubmed..Here we review macrophage responses to oxidized lipoproteins and provide novel data on the effects of a major oxidation product, 7-ketocholesterol, on high-density lipoprotein (HDL) function in cholesterol removal from macrophages. ..
- 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. ..
- Moreira E, Larrayoz I, Lee J, RodrÃguez I. 7-Ketocholesterol is present in lipid deposits in the primate retina: potential implication in the induction of VEGF and CNV formation. Invest Ophthalmol Vis Sci. 2009;50:523-32 pubmed publisher..The pathway for VEGF induction seems to be independent of HIF-1alpha and NF-kappaB but seems to be partially regulated by LXRs. ..
- 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. ..
- Terasaka N, Wang N, Yvan Charvet L, Tall A. High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1. Proc Natl Acad Sci U S A. 2007;104:15093-8 pubmed..These findings indicate a specific role for ABCG1 in promoting efflux of 7-ketocholesterol and related oxysterols from macrophages onto HDL and in protecting these cells from oxysterol-induced cytotoxicity...
- Larrayoz I, Huang J, Lee J, Pascual I, Rodriguez I. 7-ketocholesterol-induced inflammation: involvement of multiple kinase signaling pathways via NF?B but independently of reactive oxygen species formation. Invest Ophthalmol Vis Sci. 2010;51:4942-55 pubmed publisher..The results of this study suggest that 7KCh activates these pathways through interactions in the plasma membrane, but the mechanism(s) remains unknown. ..
- Luchian T, Mereuta L. Phlorizin- and 6-ketocholestanol-mediated antagonistic modulation of alamethicin activity in phospholipid planar membranes. Langmuir. 2006;22:8452-7 pubmed
- Leonarduzzi G, Vizio B, Sottero B, Verde V, Gamba P, Mascia C, et al. Early involvement of ROS overproduction in apoptosis induced by 7-ketocholesterol. Antioxid Redox Signal. 2006;8:375-80 pubmed..In fact, two metabolic inhibitors of NADPH-oxidase and the antioxidant epicatechin very well counteracted 7-ketocholesterol-induced apoptosis by preventing the oxysterol pro-oxidant action. ..
- Freeman N, Rusinol A, Linton M, Hachey D, Fazio S, Sinensky M, et al. Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages. J Lipid Res. 2005;46:1933-43 pubmed..These results suggest that 7KC not only initiates the apoptosis pathway by activating cPLA2, as we have reported previously, but also participates in the downstream signaling pathway when esterified by ACAT to form 7KC-arachidonate. ..
- Royer M, Lemaire Ewing S, Desrumaux C, Monier S, Pais de Barros J, Athias A, et al. 7-ketocholesterol incorporation into sphingolipid/cholesterol-enriched (lipid raft) domains is impaired by vitamin E: a specific role for alpha-tocopherol with consequences on cell death. J Biol Chem. 2009;284:15826-34 pubmed publisher..Akt-PKB dephosphorylation was prevented by alpha-tocopherol, but not gamma-tocopherol pretreatment. ..
- Massey J, Pownall H. The polar nature of 7-ketocholesterol determines its location within membrane domains and the kinetics of membrane microsolubilization by apolipoprotein A-I. Biochemistry. 2005;44:10423-33 pubmed..Compared to cholesterol, 7-ketocholesterol can differentially modulate membrane properties involved in protein-membrane association and function. ..
- Amaral J, Lee J, Chou J, Campos M, Rodriguez I. 7-Ketocholesterol induces inflammation and angiogenesis in vivo: a novel rat model. PLoS ONE. 2013;8:e56099 pubmed publisher..In summary this study demonstrates two important things: 1) 7KCh is pro-angiogenic and pro-inflammatory in vivo and 2) implants containing 7KCh may be used to create a novel angiogenesis model in rats. ..
- Seet R, Lee C, Loke W, Huang S, Huang H, Looi W, et al. Biomarkers of oxidative damage in cigarette smokers: which biomarkers might reflect acute versus chronic oxidative stress?. Free Radic Biol Med. 2011;50:1787-93 pubmed publisher..Thus, different biomarkers do not measure identical aspects of oxidative stress. ..
- Wong D, Wang M. Inhibitory activities of some vitamins on the formation of cholesterol oxidation products in beef patties. J Agric Food Chem. 2013;61:8471-6 pubmed publisher..This type of reaction was also found to occur in beef patties by chromatographic and spectral analyses. ..
- Berliner J, Zimman A. Future of toxicology--lipidomics, an important emerging area for toxicologists: focus on lipid oxidation products. Chem Res Toxicol. 2007;20:849-53 pubmed
- Vitha M, Clarke R. Comparison of excitation and emission ratiometric fluorescence methods for quantifying the membrane dipole potential. Biochim Biophys Acta. 2007;1768:107-14 pubmed..Di-8-ANEPPS can, thus, only be used via an excitation ratiometric method to quantify the dipole potential. ..
- Vejux A, Kahn E, Dumas D, Bessède G, Menetrier F, Athias A, et al. 7-Ketocholesterol favors lipid accumulation and colocalizes with Nile Red positive cytoplasmic structures formed during 7-ketocholesterol-induced apoptosis: analysis by flow cytometry, FRET biphoton spectral imaging microscopy, and subcellular fracti. Cytometry A. 2005;64:87-100 pubmed..During 7KC-induced apoptosis, 7KC modifies the cellular content of neutral and polar lipids, favors free cholesterol accumulation, and colocalizes with neutral and polar lipids that are inside NR-stained cytoplasmic structures. ..
- Csallany A, Hee Lee J, Shoeman D. Protection of superoxide-induced cholesterol oxidation by antioxidants in protic conditions. Int J Food Sci Nutr. 2002;53:403-9 pubmed..The presence of antioxidants markedly retarded the formation of 7-ketocholesterol. The formation of 7beta-hydroxycholesterol or 7alpha-hydroxycholesterol was also reduced, but to a lesser degree. ..
- Lee C, Park W, Han E, Bang H. Differential modulation of 7-ketocholesterol toxicity against PC12 cells by calmodulin antagonists and Ca2+ channel blockers. Neurochem Res. 2007;32:87-98 pubmed
- Suh M, Yoo S, Chang P, Lee H. Antioxidative activity of microencapsulated gamma-oryzanol on high cholesterol-fed rats. J Agric Food Chem. 2005;53:9747-50 pubmed..Therefore, this microencapsulation can be a good potential technique to protect the antioxidant activity of gamma-OZ from heat-induced lipid oxidation. ..
- Kasperczyk S, Birkner E, Kasperczyk A, Kasperczyk J. Lipids, lipid peroxidation and 7-ketocholesterol in workers exposed to lead. Hum Exp Toxicol. 2005;24:287-95 pubmed..4, 95%CI 1.4-14.5) was found more often. LP significantly increased by about 71% and concentration of 7-ketocholesterol by about 122% in hypertensives when compared with normotensives in the HL group. ..
- Skrzep Poloczek B, Tomasik A, Tarnawski R, Hyla Klekot L, Dyduch A, Wojciechowska C, et al. Nephrotic origin hyperlipidemia, relative reduction of vitamin E level and subsequent oxidative stress may promote atherosclerosis. Nephron. 2001;89:68-72 pubmed..We suggest that this may constitute an important link between nephrotic syndrome and atherosclerosis. ..
- Lyons M, Brown A. 7-Ketocholesterol delivered to mice in chylomicron remnant-like particles is rapidly metabolised, excreted and does not accumulate in aorta. Biochim Biophys Acta. 2001;1530:209-18 pubmed..Indeed, the data encourage further investigation into the contribution that dietary oxysterols may or may not make to atherogenesis. ..
- Saldanha T, Bragagnolo N. Cholesterol oxidation is increased and PUFA decreased by frozen storage and grilling of Atlantic hake fillets (Merluccius hubbsi). Lipids. 2007;42:671-8 pubmed