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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.
AuthorsYoude Jiang, Qiuhua Zhang, Jena J Steinle
JournalGrowth factors (Chur, Switzerland) (Growth Factors) Vol. 33 Issue 3 Pg. 192-9 ( 2015) ISSN: 1029-2292 [Electronic] England
PMID26115368 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic beta-Agonists
  • Insulin-Like Growth Factor Binding Protein 3
  • Isoenzymes
  • Phenethylamines
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Streptozocin
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • protein kinase C zeta
  • Prkcq protein, rat
  • Protein Kinase C
  • Protein Kinase C-delta
  • Protein Kinase C-theta
  • Norepinephrine
Topics
  • Adrenergic beta-Agonists (pharmacology)
  • Animals
  • Cells, Cultured
  • Diabetes Mellitus, Experimental (pathology)
  • Diabetic Retinopathy (pathology)
  • Endothelial Cells (cytology)
  • Insulin-Like Growth Factor Binding Protein 3 (genetics)
  • Isoenzymes (metabolism)
  • Macular Edema (pathology)
  • Male
  • Nitric Oxide Synthase Type III (metabolism)
  • Norepinephrine (analogs & derivatives, pharmacology)
  • Phenethylamines (pharmacology)
  • Protein Kinase C (metabolism)
  • Protein Kinase C-delta (metabolism)
  • Protein Kinase C-theta
  • RNA Interference
  • RNA, Small Interfering (genetics)
  • Rats
  • Rats, Inbred Lew
  • Retina (cytology, pathology)
  • Streptozocin
  • Vascular Endothelial Growth Factor A (metabolism)

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