May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Nitric Oxide (NO) and Carbon Monoxide (CO) Regulate Vasodilator–Stimulated Phosphoprotein (VASP), a Key Cytoskeletal Protein Involved in Endothelial Progenitor Cell (EPC) Migration
Author Affiliations & Notes
  • K.–H. Chang
    University of Florida, Gainesville, FL
    Pharmacology & Therapeutics,
  • A. Afzal
    University of Florida, Gainesville, FL
    Pharmacology & Therapeutics,
  • S. LiCalzi
    University of Florida, Gainesville, FL
    Pharmacology & Therapeutics,
  • M.S. Segal
    University of Florida, Gainesville, FL
    Medicine,
  • D.L. Purich
    University of Florida, Gainesville, FL
    Biochemistry,
  • M.B. Grant
    University of Florida, Gainesville, FL
    Pharmacology & Therapeutics,
  • Footnotes
    Commercial Relationships  K. Chang, None; A. Afzal, None; S. LiCalzi, None; M.S. Segal, None; D.L. Purich, None; M.B. Grant, None.
  • Footnotes
    Support  NIH 2R01 EY07739–14A1, NIH 5R01 EY12601–5 and the Juvenile Diabetes Research Foundation
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 1710. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      K.–H. Chang, A. Afzal, S. LiCalzi, M.S. Segal, D.L. Purich, M.B. Grant; Nitric Oxide (NO) and Carbon Monoxide (CO) Regulate Vasodilator–Stimulated Phosphoprotein (VASP), a Key Cytoskeletal Protein Involved in Endothelial Progenitor Cell (EPC) Migration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1710.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Within EPCs, we have shown that NO has a critical function in regulating the distribution of the motor protein VASP, which plays a critical role in actin–based motility. Reduced NO bioavailability alters actin polymerization, affecting EPC migration and EPC–mediated vascular repair leading to development of acellular capillaries (Diabetes 2005). CO generated from heme by heme oxygenases regulates NO and is cytoprotective. We investigated whether CO promotes cytoskeletal changes through VASP phosphorylation and redistribution.

Methods: : EPC (CD34+) cells were isolated from human peripheral blood of 10 diabetic and 10 nondiabetic individuals using magnetic microbeads. Cells from each individual were treated for 15 min and 4h with CO and NO donors, tricarbonyldichlororuthenium dimer and DETA NO, respectively, permeabilized and stained with anti–phospho–VASP antibody (2.4 µg/ml). Immunohistochemistry was performed with anti–VASP antibody.

Results: : Levels of phosphorylated VASP were increased in both normal and diabetic CD34+ cells following exposure of the NO donor; however, VASP activation was greater in nondiabetics than diabetic (p<0.001). VASP was redistributed to the peripheral membrane and filipodia in response to incubation with either NO or CO donor.

Conclusions: : The defective migratory properties of diabetic EPCs appear to result from reduced VASP phosphorylation. CO can compensate for NO in states of NO deficiency (such as diabetes) by promoting cytoskeletal changes through phosphorylation of VASP and by increasing EPC migration for proper capillary repair.

Keywords: nitric oxide • signal transduction • drug toxicity/drug effects 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×