Oxysterols Induced Inflammation and Oxidation in Primary Porcine Retinal Pigment Epithelial Cells

Joffre, Corinne; Leclère, Laurent; Buteau, Bénédicte; Martine, Lucy; Cabaret, Stéphanie; Malvitte, L.; Acar, Niyazi; Lizard, Gérard; Bron, Alain M.; Creuzot‐Garcher, Catherine; Brétillon, Lionel

doi:10.1080/02713680601187951

Cited by 69 publications

(50 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The addition of exogenous cytochrome c and ATP to a cell-free system also resulted in cleavage of caspase-3 and -9 in extracts of U937 but not ARPE19 cells ( 122 ). Similarly, when ARPE19 cells were subjected to VEGF and IL-8 ( 8,9 ). However, the pathway by which these cytokines are induced does not seem to involve ROS ( 8, 9, 100 , 101 ).…”

Section: -Ketocholesterol In Chronic Infl Ammation and Agingmentioning

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

View full text Add to dashboard Cite

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...

show abstract

Section: -Ketocholesterol In Chronic Infl Ammation and Agingmentioning

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

View full text Add to dashboard Cite

show abstract

“…Additionally, 24-OH significantly induces ROS production determined in primary porcine retinal pigment epithelial cells. (Joffre et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Association of CYP39A1, RUNX2 and Oxidized Alpha-1 Antitrypsin Expression in Relation to Cholangiocarcinoma Progression

Khenjanta

Thanan²,

Jusakul³

et al. 2015

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Cytochrome P450 (CYP) enzymes are a large family of constitutive and inducible mono-oxygenase enzymes that play a central role in the oxidative metabolism of both xenobiotic and endogenous compounds. Several CYPs are involved in metabolism of oxysterols, which are cholesterol oxidation products whose expression may be dysregulated in inflammation-related diseases including cancer. This study focused on CYP39A1, which can metabolize 24-hydroxycholesterol (24-OH) that plays important roles in the inflammatory response and oxidative stress. We aimed to investigate the expression status of CYP39A1 and its transcription factor (RUNX2) in relation to clinical significance in cholangiocarcinoma (CCAs) and to determine whether 24-OH could induce oxidative stress in CCA cell lines. Immunohistochemistry showed that 70% and 30% of CCA patients had low and high expression of CYP39A1, respectively. Low expression of CYP39A1 demonstrated a significant correlation with metastasis. Our results also revealed that the expression of RUNX2 had a positive correlation with CYP39A1. Low expression of both CYP39A1 (70%) and RUNX2 (37%) was significantly related with poor prognosis of CCA patients. Interestingly, oxidized alpha-1 antitrypsin (ox-A1AT), an oxidative stress marker, was significantly increased in CCA tissues in which CYP39A1 and RUNX2 were down regulated. Additionally, immunocytochemistry showed that 24-OH could induce ox-A1AT in CCA cell lines. In conclusion, our study revealed putative roles of the CYP39A1 enzyme in prognostic determination of CCAs.

show abstract

“…However, some reports indicate that oxysterol influences proinflammatory properties (Wang N et al, 1996;Liu Y et al, 1997). Joffre et al reported that 7KCHO enhanced interleukin-8 gene expression using porcine retinal pigment epithelial cells (Joffre C et al, 2007). Interleukin-8 is a proinflammatory and chemotactic cytokine which might play a crucial role in the recruitment of monocytes and T lymphocytes into the arterial subendothelial space, consequently, promoting atherosclerotic lesion (Terkeltaub R et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Relatioship Between Serum 7-Ketocholesterol Concentrations and Coronary Artery Disease

Hatori¹,

Shirai²

2012

Coronary Artery Diseases

View full text Add to dashboard Cite

Oxysterols Induced Inflammation and Oxidation in Primary Porcine Retinal Pigment Epithelial Cells

Abstract: We conclude that in confluent primary porcine RPE cells, 24-hydroxycholesterol, 25-hydroxycholesterol, and 7-ketocholesterol are potent inducers of oxidation and inflammation.

Cited by 69 publications

References 43 publications

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

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

Association of CYP39A1, RUNX2 and Oxidized Alpha-1 Antitrypsin Expression in Relation to Cholangiocarcinoma Progression

Relatioship Between Serum 7-Ketocholesterol Concentrations and Coronary Artery Disease

Contact Info

Product

Resources

About