Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis

Véjux, Anne; Lizard, Gérard

doi:10.1016/j.mam.2009.02.006

Cited by 250 publications

(212 citation statements)

References 266 publications

(298 reference statements)

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“…If deuterated 7-DHC is added to a plasma sample when it is taken, the ratio of a deuterated ( d 7 ) to undeuterated ( d 0 ) oxysterol in the sample, when compared with the ratio endothelial growth factor (29)(30)(31). Levels of 7-ketocholesterol are also elevated in patients with Niemann-Pick disease type C1 ( 32 ).…”

Section: Ex Vivo Oxidation and Sterol Oxysterols In Slos Plasmamentioning

confidence: 99%

Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients

Liu

Lamberson

et al. 2013

Journal of Lipid Research

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Section: Ex Vivo Oxidation and Sterol Oxysterols In Slos Plasmamentioning

confidence: 99%

Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients

Liu

Lamberson

et al. 2013

Journal of Lipid Research

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“…7KCh is an oxidized form of cholesterol commonly found in oxidized LDL (oxLDL) associated with atherosclerotic plaques (1)(2)(3)(4)(5)(6)(7)(23)(24)(25). 7KCh has been shown to have potent proinfl ammatory and cell death properties and has been implicated in foam cell formation in macrophages ( 2,4,7,(23)(24)(25).…”

Section: What Is 7kch?mentioning

confidence: 99%

Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration

Rodríguez

Larráyoz

2010

Journal of Lipid Research

121

115

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Journal of Lipid Research Volume 51, 20102847 their actions affect the retina and the retinal pigment epithelium (RPE) ( 8-10 ). One particular oxysterol, 7-ketocholesterol (7KCh), has been found more abundantly than other oxysterols in the retina ( 9, 10 ). This oxysterol is known to have potent pharmacological properties that lead to infl ammation and cell death in a variety of cell types ( 1-10 ). This review will focus on what is known about this molecule and the potential implications of its presence in the retina. The retina is a light-capturing tissue that contains at least 5 cell classes and more than 50 different cell types, each performing unique functions that ultimately provide the visual centers in the brain the information to achieve image formation and visual perception. The retina faces a unique photooxidative environment that generates challenges not encountered by other neurological tissues or organs. Phototransduction requires the retina to have a high metabolic rate ( 11 ) and multiple and complex membrane structures ( 12 ). The photoreceptor outer segments are enriched in the highly photosensitive docosahexaenoic acid and other Abstract This review will discuss the formation and potential implications of 7-ketocholesterol (7KCh) in the retina. 7KCh is a proinfl ammatory oxysterol known to be present in high amounts in oxidized LDL deposits associated with atheromatous plaques. 7KCh is generated in situ in these lipoprotein deposits where it can accumulate and reach very high concentrations. In normal primate retina, 7KCh has been found associated with lipoprotein deposits in the choriocapillaris, Bruch's membrane, and the retinal pigment epithelium (RPE). In photodamaged rats, 7KCh has been found in the neural retina in areas of high mitochondrial content, ganglion cells, photoreceptor inner segments and synapses, and the RPE. Intermediates found by LCMS indicate 7KCh is formed via a free radical-mediated mechanism catalyzed by iron. 7KCh seems to activate several kinase signaling pathways that work via nuclear factor B and cause the induction of vascular endothelial growth factor, interleukin (IL)-6, and IL-8. There seems to be little evidence of 7KCh metabolism in the retina, although some form of effl ux mechanism may be active. The chronic mode of formation and the potent infl ammatory 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. -Rodríguez, I. R., and I. M. Larrayoz. Cholesterol oxidation in the retina: implications of 7-KCh formation in chronic infl ammation and age-related macular degeneration. J. Lipid Res . 2010. 51: 2847-2862. Supplementary key words 7-ketocholesterol • cytokines • oxysterolsIn the past year, numerous reviews have been published that extensively discuss the multiple functions of oxysterols and their complex relationships to diseases ( 1-7 ). However, the formation and function of oxysterols in the retina has not been well studied. Emerging studies are...

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“…With regard to oxysterols, there is considerable interest in this general class of compounds because of their presence in humans and their biological properties (15)(16)(17)(18)(19). One oxysterol of interest is 7-ketocholesterol, which is a strong inhibitor of cytochrome P450 7A1, the cholesterol 7␣-hydroxylase (IC 50 ϳ 1 M) (20).…”

mentioning

confidence: 99%

“…7-Ketocholesterol can also exert biological activities, e.g. regulation of cholesterol homeostasis, cytotoxicity, and apoptosis and induction of inflammation, growth inhibition, and vascular endothelial growth factor (16,19,(21)(22)(23)(24). The level of 7-ketocholesterol in human plasma is about one-half that of 7␣-hydroxycholesterol, the product of the first committed step of bile acid synthesis (16,(25)(26)(27).…”

mentioning

confidence: 99%

Conversion of 7-Dehydrocholesterol to 7-Ketocholesterol Is Catalyzed by Human Cytochrome P450 7A1 and Occurs by Direct Oxidation without an Epoxide Intermediate

Shinkyo

Tallman

et al. 2011

Journal of Biological Chemistry

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Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis

Cited by 250 publications

References 266 publications

Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients

Assays of plasma dehydrocholesteryl esters and oxysterols from Smith-Lemli-Opitz syndrome patients

Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration

Conversion of 7-Dehydrocholesterol to 7-Ketocholesterol Is Catalyzed by Human Cytochrome P450 7A1 and Occurs by Direct Oxidation without an Epoxide Intermediate

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