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المؤلفIbrahim, Ahmed S.
المؤلفElshafey, Sally
المؤلفSellak, Hassan
المؤلفHussein, Khaled A.
المؤلفEl-Sherbiny, Mohamed
المؤلفAbdelsaid, Mohammed
المؤلفRizk, Nasser
المؤلفBeasley, Selina
المؤلفTawfik, Amany M.
المؤلفSmith, Sylvia B.
المؤلفAl-Shabrawey, Mohamed
تاريخ الإتاحة2016-11-21T09:49:37Z
تاريخ النشر2015-03
اسم المنشورJournal of Lipid Research
المعرّفhttp://dx.doi.org/ 10.1194/jlr.M056069
الاقتباسIbrahim AS, Elshafey S, Sellak H, et al. A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase. Journal of Lipid Research. 2015;56(3):599-611.
الرقم المعياري الدولي للكتاب0022-2275
معرّف المصادر الموحدhttp://hdl.handle.net/10576/5030
الملخصRetinal hyperpermeability and subsequent macular edema is a cardinal feature of early diabetic retinopathy (DR). Here, we investigated the role of bioactive lipid metabolites, in particular 12/15-lipoxygenase (LOX)-derived metabolites, in this process. LC/MS lipidomic screen of human retinal endothelial cells (HRECs) demonstrated that 15-HETE was the only significantly increased metabolite (2.4 ± 0.4-fold, P = 0.0004) by high glucose (30 mM) treatment. In the presence of arachidonic acid, additional eicosanoids generated by 12/15-LOX, including 12- and 11-HETEs, were significantly increased. Fluorescein angiography and retinal albumin leakage showed a significant decrease in retinal hyperpermeability in streptozotocin-induced diabetic mice lacking 12/15-LOX compared with diabetic WT mice. Our previous studies demonstrated the potential role of NADPH oxidase in mediating the permeability effect of 12- and 15-HETEs, therefore we tested the impact of intraocular injection of 12-HETE in mice lacking the catalytic subunit of NADPH oxidase (NOX2). The permeability effect of 12-HETE was significantly reduced in NOX2−/− mice compared with the WT mice. In vitro experiments also showed that 15-HETE induced HREC migration and tube formation in a NOX-dependent manner. Taken together our data suggest that 12/15-LOX is implicated in DR via a NOX-dependent mechanism.
راعي المشروعNational Institutes of Health Grant 5R01EY023315 and National Priorities Research Program Grant 4-1046-3-284 from the Qatar National Research Fund (a member of Qatar Foundation). This study was also supported in part by the National Center for Research Resources, National Institutes of Health Grant S10RR027926.
اللغةen
الناشرAmerican Society for Biochemistry and Molecular Biology
الموضوعbioactive lipids
diabetic retinopathy
lipoxygenase
reduced nicotinamide adenine dinucleotide phosphate oxidase
retinal inflammation
retinal vascular leakage
العنوانA lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase
النوعArticle
الصفحات599-611
رقم العدد3
رقم المجلد56
ESSN1539-7262
dc.accessType Open Access


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