title: Beta-adrenergic receptor agonist decreases VEGF levels through altered eNOS and PKC signaling in diabetic retina.
abstract: Vascular endothelial cell growth factor (VEGF) is increased in diabetic macular edema. Compound 49b, a novel β-adrenergic receptor agonist, is protective in a type 1 diabetic rat model. We questioned whether Compound 49b could decrease VEGF levels, suggesting that Compound 49b may be effective against edema. Two-month diabetic rats received topical Compound 49b for 7 days only and/or insulin-like growth factor binding protein 3 (IGFBP-3) siRNA. We also measured endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC)ζ and PKCδ phosphorylation. Retinal endothelial cells (RECs) cultured in high glucose were treated with Compound 49b and IGFBP-3 siRNA for evaluation of the same signaling pathways. Compound 49b significantly decreased VEGF through increased IGFBP-3 in the diabetic retina. Compound 49b also reduced eNOS, PKCζ and PKCδ phosphorylation in the diabetic retina and REC. Compound 49b regulated a number of proteins involved in REC barrier properties.
authors.affiliation: a Department of Anatomy and Cell Biology , Wayne State University , Detroit , MI , USA .
authors.forename: Youde
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: b Department of Ophthalmology , University of Tennessee Health Science Center , Memphis , TN , USA , and.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: a Department of Anatomy and Cell Biology , Wayne State University , Detroit , MI , USA .|c Department of Ophthalmology , Wayne State University , Detroit , MI , USA.
authors.forename: Jena J
authors.initials: JJ
authors.lastname: Steinle
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000473:pathology*; D042783:Endothelial Cells / Q000166:cytology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007527:Isoenzymes / Q000378:metabolism; D008269:Macular Edema / Q000473:pathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism; D000074121:Protein Kinase C-theta; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000166:cytology / Q000473:pathology; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099221:Protein Kinase C zeta
chemical_list: D000318:Adrenergic beta-Agonists; D018972:Insulin-Like Growth Factor Binding Protein 3; D007527:Isoenzymes; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine; D010627:Phenethylamines; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D000074121:Protein Kinase C-theta; D034741:RNA, Small Interfering; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A; D000099221:Protein Kinase C zeta; C467498:vascular endothelial growth factor A, rat; C496316:Nos3 protein, rat; C489591:Prkcq protein, rat
keywords: Beta-adrenergic receptor; VEGF; diabetic retinopathy