12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase
<p dir="ltr">The purpose of the current study was to evaluate the effect of 12/15- lipoxygenase (12/15-LOX) metabolites on retinal endothelial cell (REC) barrier function. FITC-dextran flux across the REC monolayers and electrical cell-substrate impedance sensing (ECIS) were used to...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , |
| منشور في: |
2013
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| الموضوعات: | |
| الوسوم: |
إضافة وسم
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| _version_ | 1864513511384678400 |
|---|---|
| author | Amira Othman (380131) |
| author2 | Saif Ahmad (371052) Sylvia Megyerdi (380132) Rene Mussell (380133) Karishma Choksi (380134) Krishna Rao Maddipati (10950942) Ahmed Elmarakby (380136) Nasser Rizk (380137) Mohamed Al-Shabrawey (380138) |
| author2_role | author author author author author author author author |
| author_facet | Amira Othman (380131) Saif Ahmad (371052) Sylvia Megyerdi (380132) Rene Mussell (380133) Karishma Choksi (380134) Krishna Rao Maddipati (10950942) Ahmed Elmarakby (380136) Nasser Rizk (380137) Mohamed Al-Shabrawey (380138) |
| author_role | author |
| dc.creator.none.fl_str_mv | Amira Othman (380131) Saif Ahmad (371052) Sylvia Megyerdi (380132) Rene Mussell (380133) Karishma Choksi (380134) Krishna Rao Maddipati (10950942) Ahmed Elmarakby (380136) Nasser Rizk (380137) Mohamed Al-Shabrawey (380138) |
| dc.date.none.fl_str_mv | 2013-02-20T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pone.0057254 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/12_15-Lipoxygenase-Derived_Lipid_Metabolites_Induce_Retinal_Endothelial_Cell_Barrier_Dysfunction_Contribution_of_NADPH_Oxidase/26018509 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Medical biochemistry and metabolomics Ophthalmology and optometry Diabetes mellitus Retina Inflammation Endothelial cells Lipid metabolism Mouse models Vascular permeability Metabolites |
| dc.title.none.fl_str_mv | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">The purpose of the current study was to evaluate the effect of 12/15- lipoxygenase (12/15-LOX) metabolites on retinal endothelial cell (REC) barrier function. FITC-dextran flux across the REC monolayers and electrical cell-substrate impedance sensing (ECIS) were used to evaluate the effect of 12- and 15-hydroxyeicosatetreanoic acids (HETE) on REC permeability and transcellular electrical resistance (TER). Effect of 12- or 15-HETE on the levels of zonula occludens protein 1 (ZO-1), reactive oxygen species (ROS), NOX2, pVEGF-R2 and pSHP1 was examined in the presence or absence of inhibitors of NADPH oxidase. In vivo studies were performed using Ins<sup>2Akita</sup> mice treated with or without the 12/15-LOX inhibitor baicalein. Levels of HETE and inflammatory mediators were examined by LC/MS and Multiplex Immunoassay respectively. ROS generation and NOX2 expression were also measured in mice retinas. 12- and 15- HETE significantly increased permeability and reduced TER and ZO-1expression in REC. VEGF-R2 inhibitor reduced the permeability effect of 12-HETE. Treatment of REC with HETE also increased ROS generation and expression of NOX2 and pVEGF-R2 and decreased pSHP1 expression. Treatment of diabetic mice with baicalein significantly decreased retinal HETE, ICAM-1, VCAM-1, IL-6, ROS generation, and NOX2 expression. Baicalein also reduced pVEGF-R2 while restored pSHP1 levels in diabetic retina. Our findings suggest that 12/15-LOX contributes to vascular hyperpermeability during DR via NADPH oxidase dependent mechanism which involves suppression of protein tyrosine phosphatase and activation of VEGF-R2 signal pathway.</p><h2>Other Information</h2><p dir="ltr">Published in: PLoS ONE<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1371/journal.pone.0057254" target="_blank">https://dx.doi.org/10.1371/journal.pone.0057254</a></p><p dir="ltr">Additional institutions affiliated with: College of Science - QU (1977-2004/2005), College of Arts and Sciences - QU (2004/05-2016).</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_6a583f19dde096a67f0038d4196169fc |
| identifier_str_mv | 10.1371/journal.pone.0057254 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26018509 |
| publishDate | 2013 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH OxidaseAmira Othman (380131)Saif Ahmad (371052)Sylvia Megyerdi (380132)Rene Mussell (380133)Karishma Choksi (380134)Krishna Rao Maddipati (10950942)Ahmed Elmarakby (380136)Nasser Rizk (380137)Mohamed Al-Shabrawey (380138)Biomedical and clinical sciencesMedical biochemistry and metabolomicsOphthalmology and optometryDiabetes mellitusRetinaInflammationEndothelial cellsLipid metabolismMouse modelsVascular permeabilityMetabolites<p dir="ltr">The purpose of the current study was to evaluate the effect of 12/15- lipoxygenase (12/15-LOX) metabolites on retinal endothelial cell (REC) barrier function. FITC-dextran flux across the REC monolayers and electrical cell-substrate impedance sensing (ECIS) were used to evaluate the effect of 12- and 15-hydroxyeicosatetreanoic acids (HETE) on REC permeability and transcellular electrical resistance (TER). Effect of 12- or 15-HETE on the levels of zonula occludens protein 1 (ZO-1), reactive oxygen species (ROS), NOX2, pVEGF-R2 and pSHP1 was examined in the presence or absence of inhibitors of NADPH oxidase. In vivo studies were performed using Ins<sup>2Akita</sup> mice treated with or without the 12/15-LOX inhibitor baicalein. Levels of HETE and inflammatory mediators were examined by LC/MS and Multiplex Immunoassay respectively. ROS generation and NOX2 expression were also measured in mice retinas. 12- and 15- HETE significantly increased permeability and reduced TER and ZO-1expression in REC. VEGF-R2 inhibitor reduced the permeability effect of 12-HETE. Treatment of REC with HETE also increased ROS generation and expression of NOX2 and pVEGF-R2 and decreased pSHP1 expression. Treatment of diabetic mice with baicalein significantly decreased retinal HETE, ICAM-1, VCAM-1, IL-6, ROS generation, and NOX2 expression. Baicalein also reduced pVEGF-R2 while restored pSHP1 levels in diabetic retina. Our findings suggest that 12/15-LOX contributes to vascular hyperpermeability during DR via NADPH oxidase dependent mechanism which involves suppression of protein tyrosine phosphatase and activation of VEGF-R2 signal pathway.</p><h2>Other Information</h2><p dir="ltr">Published in: PLoS ONE<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1371/journal.pone.0057254" target="_blank">https://dx.doi.org/10.1371/journal.pone.0057254</a></p><p dir="ltr">Additional institutions affiliated with: College of Science - QU (1977-2004/2005), College of Arts and Sciences - QU (2004/05-2016).</p>2013-02-20T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1371/journal.pone.0057254https://figshare.com/articles/journal_contribution/12_15-Lipoxygenase-Derived_Lipid_Metabolites_Induce_Retinal_Endothelial_Cell_Barrier_Dysfunction_Contribution_of_NADPH_Oxidase/26018509CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260185092013-02-20T06:00:00Z |
| spellingShingle | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase Amira Othman (380131) Biomedical and clinical sciences Medical biochemistry and metabolomics Ophthalmology and optometry Diabetes mellitus Retina Inflammation Endothelial cells Lipid metabolism Mouse models Vascular permeability Metabolites |
| status_str | publishedVersion |
| title | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase |
| title_full | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase |
| title_fullStr | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase |
| title_full_unstemmed | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase |
| title_short | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase |
| title_sort | 12/15-Lipoxygenase-Derived Lipid Metabolites Induce Retinal Endothelial Cell Barrier Dysfunction: Contribution of NADPH Oxidase |
| topic | Biomedical and clinical sciences Medical biochemistry and metabolomics Ophthalmology and optometry Diabetes mellitus Retina Inflammation Endothelial cells Lipid metabolism Mouse models Vascular permeability Metabolites |