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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
