May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Vasoinhibins Inhibit VEGF-Induced Vasopermeability via Protein Phosphatase 2A-Dependent eNOS Inactivation
Author Affiliations & Notes
  • C. Garcia
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • E. Arnold
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • S. Thebault
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • G. Martinez de la Escalera
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • C. Clapp
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • Footnotes
    Commercial Relationships  C. Garcia, None; E. Arnold, None; S. Thebault, None; G. Martinez de la Escalera, None; C. Clapp, None.
  • Footnotes
    Support  CONACYT grant 49292
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1348. doi:https://doi.org/
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      C. Garcia, E. Arnold, S. Thebault, G. Martinez de la Escalera, C. Clapp; Vasoinhibins Inhibit VEGF-Induced Vasopermeability via Protein Phosphatase 2A-Dependent eNOS Inactivation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1348. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Vasoinhibins are a family of peptides derived from prolactin that antagonize the proangiogenic effects of VEGF, a primary mediator of vascular permeability. VEGF signaling involves endothelial nitric oxide synthase (eNOS) phosphorylation at Ser1179. Here, we investigated whether vasoinhibins block VEGF-induced vasopermeability by promoting the dephosphorylation of eNOS. Because protein phosphatase 2A (PP2A) is known to dephosphorylate eNOS at Ser1179, we further analyzed whether vasoinhibins dephosphorylate/inactivate eNOS by activating PP2A.

Methods: : Bovine aortic endothelial cell (BAEC) monolayers were treated with VEGF in the presence or the absence of vasoinhibins. Vasopermeability was measured by the leakage of horseradish peroxidase across BAEC monolayers. Phosphorylation and eNOS activity were examined by Western blot and the [3H]L-citrulline assay, respectively. PP2A activity was determined by the release of phosphate from a PP2A-specific substrate.

Results: : Vasoinhibins inhibited VEGF-induced endothelial cell permeability, and this effect was similar to blockage of NO synthesis with L-NAME. Vasoinhibins prevented both VEGF-induced eNOS phosphorylation at Ser1179 and eNOS activation. Vasoinhibins activated PP2A in BAEC, and okadaic acid, a PP2A inhibitor, blocked the vasoinhibin effect on eNOS phosphorylation, eNOS activity, and vasopermeability.

Conclusions: : The present study shows that vasoinhibins prevent VEGF-induced permeability in BAEC. This action involves the inhibition of VEGF-induced eNOS activation via PP2A-dependent dephosphorylation of eNOS. As diabetic macular edema is characterized by excessive VEGF-induced vasopermeability, our findings suggest that vasoinhibins may be developed as protective agents against this disease.

Keywords: diabetic retinopathy • nitric oxide • vascular endothelial growth factor 
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