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 Citations (Scopus)

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 2005
Externally publishedYes

Fingerprint

Galactosemias
Endothelial cells
Galactose
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Stem cells
Animals
Hematopoietic Stem Cells
Superoxides
Nitric Oxide
Peroxynitrous Acid
Oxidative stress
Blood Vessels
Biomarkers
Pathology
Protein Isoforms
Fluorescence
Endothelial Progenitor Cells
Diabetic Retinopathy
Retina

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

Nitric oxide synthases modulate progenitor and resident endothelial cell behavior in galactosemia. / Ellis, E. Ann; Sengupta, Nilanjana; Caballero, Sergio; Guthrie, Steven M.; Mames, Robert N.; Grant, Maria B.

In: Antioxidants and Redox Signaling, Vol. 7, No. 11-12, 11.2005, p. 1413-1422.

Research output: Contribution to journalArticle

Ellis, EA, Sengupta, N, Caballero, S, Guthrie, SM, Mames, RN & Grant, MB 2005, 'Nitric oxide synthases modulate progenitor and resident endothelial cell behavior in galactosemia', Antioxidants and Redox Signaling, vol. 7, no. 11-12, pp. 1413-1422. https://doi.org/10.1089/ars.2005.7.1413
Ellis, E. Ann ; Sengupta, Nilanjana ; Caballero, Sergio ; Guthrie, Steven M. ; Mames, Robert N. ; Grant, Maria B. / Nitric oxide synthases modulate progenitor and resident endothelial cell behavior in galactosemia. In: Antioxidants and Redox Signaling. 2005 ; Vol. 7, No. 11-12. pp. 1413-1422.
@article{725cb8d3883d4357bdb247e0075dc0d7,
title = "Nitric oxide synthases modulate progenitor and resident endothelial cell behavior in galactosemia",
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.",
author = "Ellis, {E. Ann} and Nilanjana Sengupta and Sergio Caballero and Guthrie, {Steven M.} and Mames, {Robert N.} and Grant, {Maria B.}",
year = "2005",
month = "11",
doi = "10.1089/ars.2005.7.1413",
language = "English (US)",
volume = "7",
pages = "1413--1422",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "11-12",

}

TY - JOUR

T1 - Nitric oxide synthases modulate progenitor and resident endothelial cell behavior in galactosemia

AU - Ellis, E. Ann

AU - Sengupta, Nilanjana

AU - Caballero, Sergio

AU - Guthrie, Steven M.

AU - Mames, Robert N.

AU - Grant, Maria B.

PY - 2005/11

Y1 - 2005/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=28844509273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28844509273&partnerID=8YFLogxK

U2 - 10.1089/ars.2005.7.1413

DO - 10.1089/ars.2005.7.1413

M3 - Article

C2 - 16356104

AN - SCOPUS:28844509273

VL - 7

SP - 1413

EP - 1422

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 11-12

ER -