No abstract

Sympathetic nerves may play a role in vascular disorders of the eye. In the present study, we hypothesized that activation of ␤ 3 -adrenergic receptors on retinal endothelial cells would promote migration and proliferation of these cells, two markers of an angiogenic phenotype. We show, for the first time, expression of ␤ 3 -adrenergic receptors on cultured retinal endothelial cells. Activation of these receptors with BRL37344, a specific ␤ 3 -adrenergic receptor agonist, promoted migration that was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K), the mitogen activated protein kinase component MEK, and matrix metalloproteinases (MMPs) 2 and 9. BRL37344 stimulated proliferation, which could be blocked by inhibitors of Src, PI3K, and MEK. These cells also express the ␤ 1 -adrenergic receptor with no ␤ 2 -adrenergic receptor expression observed. Stimulation of the ␤ 1 -adrenergic receptor with xamoterol, a specific partial agonist, did not promote proliferation or migration. These results support the hypothesis that ␤ 3 -adrenergic receptors play a role in proliferation and migration of cultured human retinal endothelial cells.

No abstract

Experiments were performed to define the basis for negative regulation of STAT3 activation (i.e., Tyr705 phosphorylation) by angiotensin II in cardiomyocytes. Treatment of cardiomyocytes with angiotensin II resulted in rapid and sustained phosphorylation of STAT3 on Ser727; in contrast, STAT3 Tyr705 phosphorylation was decreased, with dephosphorylation being most pronounced at 30 minutes. Angiotensin II-induced STAT3 Tyr705 dephosphorylation was not prevented by inhibiting protein synthesis, but was blocked by vanadate or the MEK inhibitor PD98059. PD98059 was found to inhibit angiotensin II-induced Erk activation and STAT3 Ser727 phosphorylation. Angiotensin II also attenuated LIF-induced STAT3 Tyr705 phosphorylation, and this effect could be blocked with PD89059. These results are consistent with Erk-mediated STAT3 Ser727 phosphorylation leading to STAT3 Tyr705 dephosphorylation, and accounting for angiotensin II-mediated STAT3 inhibition in cardiomyocytes. We propose that Erk serves as a scaffolding protein in recruiting either a protein tyrosine or MAP kinase phosphatase to STAT3.