Nitric oxide synthases modulate progenitor and resident endothelial cell behavior in galactosemia

E. Ann Ellis, Nilanjana Sengupta, Sergio Caballero, Steven M. Guthrie, Robert N. Mames, Maria B. Grant

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

We used knockout animals of either inducible nitric oxide synthase (iNOS-/-) or endothelial NOS (eNOS-/-) to characterize the role of NOS in galactosemia, a model of diabetic retinopathy. NADH oxidase and nitrotyrosine were used as biomarkers of oxidative stress and vascular dysfunction. These animals were engrafted with hematopoietic stem cells (HSC) expressing green fluorescence protein (gfp+) to characterize the contribution of HSC and endothelial progenitor cells to neovascularization. Increased NADH oxidase activity and superoxide generation occurred in all galactose-fed mice. eNOS-/- mice demonstrated increased iNOS immunoreactivity in their retinal vasculature. Nitrotyrosine levels were low at baseline in the wild-type (WT) mice, eNOS-/- and iNOS-/- mice, and the galactose-fed iNOS mice and increased following galactose feeding in eNOS-/- and WT. Galactose-fed WT.gfp and iNOS-/-.gfp chimeric animals had areas of perfused new vessels composed of gfp+ cells. In contrast, galactose-fed eNOS-/-.gfp mice produced copious, unbranched, non-perfused tubes. Thus, nitric oxide modulates HSC behavior and vascular phenotype in the retina. Although there is increased NADH oxidase and superoxide in galactosemic mice of all isoforms, iNOS is the source of nitric oxide responsible for peroxynitrite and nitrotyrosine formation that leads to the pathology observed in galactosemic mice.

Original languageEnglish (US)
Pages (from-to)1413-1422
Number of pages10
JournalAntioxidants and Redox Signaling
Volume7
Issue number11-12
DOIs
StatePublished - Nov 1 2005

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Ellis, E. A., Sengupta, N., Caballero, S., Guthrie, S. M., Mames, R. N., & Grant, M. B. (2005). Nitric oxide synthases modulate progenitor and resident endothelial cell behavior in galactosemia. Antioxidants and Redox Signaling, 7(11-12), 1413-1422. https://doi.org/10.1089/ars.2005.7.1413