Faculty Collaboration Database

Attenuation of lipopolysaccharide-induced oxidative stress and apoptosis in fetal pulmonary artery endothelial cells by hypoxia. Free Radic Biol Med 2009 Mar 01;46(5):663-71

Date

01/13/2009

Pubmed ID

19135525

Pubmed Central ID

PMC2646363

DOI

10.1016/j.freeradbiomed.2008.12.008

Scopus ID

2-s2.0-59249092488 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Pulmonary vascular endothelial injury resulting from lipopolysaccharide (LPS) and oxygen toxicity contributes to vascular simplification seen in the lungs of premature infants with bronchopulmonary dysplasia. Whether the severity of endotoxin-induced endothelial injury is modulated by ambient oxygen tension (hypoxic intrauterine environment vs. hyperoxic postnatal environment) remains unknown. We posited that ovine fetal pulmonary artery endothelial cells (FPAEC) will be more resistant to LPS toxicity under hypoxic conditions (20-25 Torr) mimicking the fetal milieu. LPS (10 microg/ml) inhibited FPAEC proliferation and induced apoptosis under normoxic conditions (21% O(2)) in vitro. LPS-induced FPAEC apoptosis was attenuated in hypoxia (5% O(2)) and exacerbated by hyperoxia (55% O(2)). LPS increased intracellular superoxide formation, as measured by 2-hydroxyethidium (2-HE) formation, in FPAEC in normoxia and hypoxia. 2-HE formation in LPS-treated FPAEC increased in parallel with the severity of LPS-induced apoptosis in FPAEC, increasing from hypoxia to normoxia to hyperoxia. Differences in LPS-induced apoptosis between hypoxia and normoxia were abolished when LPS-treated FPAEC incubated in hypoxia were pretreated with menadione to increase superoxide production. Apocynin decreased 2-HE formation, and attenuated LPS-induced FPAEC apoptosis under normoxic conditions. We conclude that ambient oxygen concentration modulates the severity of LPS-mediated injury in FPAEC by regulating superoxide levels produced in response to LPS.

Author List

Sampath V, Radish AC, Eis AL, Broniowska K, Hogg N, Konduri GG

Authors

Neil Hogg PhD Senior Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

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

Acetophenones
Animals
Apoptosis
Bronchopulmonary Dysplasia
Cell Proliferation
Cells, Cultured
Chromatography, High Pressure Liquid
Endothelial Cells
Humans
Hypoxia
Infant, Newborn
Infant, Premature
Lipopolysaccharides
Oxidative Stress
Pulmonary Artery
Sheep
Superoxides
Vitamin K 3