A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase
Retinal 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 endothe...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-03-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520355887 |
| id |
doaj-a9eac5bb558f49d4ab2ac1cd032e6672 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Ahmed S. Ibrahim Sally Elshafey Hassan Sellak Khaled A. Hussein Mohamed El-Sherbiny Mohammed Abdelsaid Nasser Rizk Selina Beasley Amany M. Tawfik Sylvia B. Smith Mohamed Al-Shabrawey |
| spellingShingle |
Ahmed S. Ibrahim Sally Elshafey Hassan Sellak Khaled A. Hussein Mohamed El-Sherbiny Mohammed Abdelsaid Nasser Rizk Selina Beasley Amany M. Tawfik Sylvia B. Smith Mohamed Al-Shabrawey A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase Journal of Lipid Research diabetic retinopathy 12- and 15-HETEs retinal vascular leakage reduced nicotinamide adenine dinucleotide phosphate oxidase retinal inflammation lipoxygenase |
| author_facet |
Ahmed S. Ibrahim Sally Elshafey Hassan Sellak Khaled A. Hussein Mohamed El-Sherbiny Mohammed Abdelsaid Nasser Rizk Selina Beasley Amany M. Tawfik Sylvia B. Smith Mohamed Al-Shabrawey |
| author_sort |
Ahmed S. Ibrahim |
| title |
A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase |
| title_short |
A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase |
| title_full |
A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase |
| title_fullStr |
A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase |
| title_full_unstemmed |
A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase |
| title_sort |
lipidomic screen of hyperglycemia-treated hrecs links 12/15-lipoxygenase to microvascular dysfunction during diabetic retinopathy via nadph oxidase |
| publisher |
Elsevier |
| series |
Journal of Lipid Research |
| issn |
0022-2275 |
| publishDate |
2015-03-01 |
| description |
Retinal 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. |
| topic |
diabetic retinopathy 12- and 15-HETEs retinal vascular leakage reduced nicotinamide adenine dinucleotide phosphate oxidase retinal inflammation lipoxygenase |
| url |
http://www.sciencedirect.com/science/article/pii/S0022227520355887 |
| work_keys_str_mv |
AT ahmedsibrahim alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT sallyelshafey alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT hassansellak alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT khaledahussein alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT mohamedelsherbiny alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT mohammedabdelsaid alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT nasserrizk alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT selinabeasley alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT amanymtawfik alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT sylviabsmith alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT mohamedalshabrawey alipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT ahmedsibrahim lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT sallyelshafey lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT hassansellak lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT khaledahussein lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT mohamedelsherbiny lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT mohammedabdelsaid lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT nasserrizk lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT selinabeasley lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT amanymtawfik lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT sylviabsmith lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase AT mohamedalshabrawey lipidomicscreenofhyperglycemiatreatedhrecslinks1215lipoxygenasetomicrovasculardysfunctionduringdiabeticretinopathyvianadphoxidase |
| _version_ |
1721504621319421952 |
| spelling |
doaj-a9eac5bb558f49d4ab2ac1cd032e66722021-04-28T06:00:29ZengElsevierJournal of Lipid Research0022-22752015-03-01563599611A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidaseAhmed S. Ibrahim0Sally Elshafey1Hassan Sellak2Khaled A. Hussein3Mohamed El-Sherbiny4Mohammed Abdelsaid5Nasser Rizk6Selina Beasley7Amany M. Tawfik8Sylvia B. Smith9Mohamed Al-Shabrawey10Oral Biology and Anatomy, College of Dental Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA; Ophthalmology and Culver Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, Augusta, GA; Department of Clinical Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptOral Biology and Anatomy, College of Dental Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GADepartment of Anesthesiology and Perioperative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GAOral Biology and Anatomy, College of Dental Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA; Ophthalmology and Culver Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, Augusta, GAOral Biology and Anatomy, College of Dental Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA; Department of Anatomy, Faculty of Medicine,Mansoura University, Mansoura, EgyptDepartment of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GABiomedical Science Program, Faculty of Science, Qatar University, Doha, QatarOral Biology and Anatomy, College of Dental Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA; Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, GAOral Biology and Anatomy, College of Dental Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA; Ophthalmology and Culver Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, Augusta, GA; Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, GAOphthalmology and Culver Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, Augusta, GA; Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, GATo whom correspondence should be addressed; Oral Biology and Anatomy, College of Dental Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA; Ophthalmology and Culver Vision Discovery Institute, Medical College of Georgia, Georgia Regents University, Augusta, GA; Department of Anatomy, Faculty of Medicine,Mansoura University, Mansoura, Egypt; Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, GARetinal 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.http://www.sciencedirect.com/science/article/pii/S0022227520355887diabetic retinopathy12- and 15-HETEsretinal vascular leakagereduced nicotinamide adenine dinucleotide phosphate oxidaseretinal inflammationlipoxygenase |