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Nitrotyrosine impairs angiogenesis and uncouples eNOS activity of pulmonary artery endothelial cells isolated from developing sheep lungs. Pediatr Res 2011 Feb;69(2):112-7

Date

11/09/2010

Pubmed ID

21057377

Pubmed Central ID

PMC3086583

DOI

10.1203/PDR.0b013e318204dcb8

Scopus ID

2-s2.0-79951648994   12 Citations

Abstract

Infection is known to impair the growth of developing lungs. It is known that plasma free nitrotyrosine (NT) levels can reach 150 μM during sepsis. Free NT incorporates into microtubules and impairs cell function. We hypothesize that free NT perturbs the angiogenic activity of pulmonary artery endothelial cells (PAEC) in developing lungs. PAEC from fetal lamb lungs were incubated with NT (1-100 μM). We examined the effects of NT on tube formation, cell proliferation, apoptosis, and α-tubulin assembly in PAEC. We assessed superoxide anion (O2) and NO levels in PAEC during NT exposure. Effects of NT on endothelial NO synthase (eNOS) were examined with respect to eNOS-dimer formation and the association of eNOS chaperone, heat-shock-protein-90 (hsp90). NT decreased tube formation and increased apoptosis in PAEC. NT also decreased NO levels, increased NOS-dependent O2 generation, and promoted α-tubulin depolymerization. Although NT increased eNOS homodimer formation, it decreased the hsp90 association with eNOS. Our data suggest that increased NT formation during sepsis may uncouple eNOS activity and increase oxidative stress. Because NO plays an important role in angiogenesis and vasodilation, these observations suggest a mechanism for the impaired vasodilation and angiogenesis during sepsis in the developing lung.

Author List

Teng RJ, Wu TJ, Bisig CG, Eis A, Pritchard KA, Konduri GG

Authors

Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
Ru-Jeng Teng MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Cell Proliferation
Cells, Cultured
Cesarean Section
Endothelial Cells
Gestational Age
HSP90 Heat-Shock Proteins
Lung
Microtubules
Neovascularization, Physiologic
Nitric Oxide
Nitric Oxide Synthase Type III
Premature Birth
Protein Multimerization
Pulmonary Artery
Sepsis
Sheep
Superoxide Dismutase
Superoxides
Tubulin
Tyrosine
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280