Attenuation of lipopolysaccharide-induced oxidative stress and apoptosis in fetal pulmonary artery endothelial cells by hypoxia |
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| Authors: | Venkatesh Sampath Aaron C Radish Annie L Eis Katarzyna Broniowska Neil Hogg Girija G Konduri |
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| Institution: | 1. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA;2. Departments of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI, USA;1. Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu, China;2. Vascular Biology Center, Augusta University, Augusta, Georgia 30912, USA;3. Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia 30912, USA;4. Department of Pharmacology, Augusta University, Augusta, Georgia 30912, USA;5. Department of Pediatrics, Children''s Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA;6. Institute for Medical Microbiology, Justus Liebig University, Germany;7. Old Dominion University, Norfolk, VA, USA;1. Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA;2. Redox Biology Program, Medical College of Wisconsin, Milwaukee, WI 53226, USA;3. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA;1. Department of Neurosciences, University of Toledo, College of Medicine and Life Science, Toledo, OH 43614, United States;2. Department of Pathology, University of Toledo, College of Medicine and Life Science, Toledo, OH 43614, United States;1. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn;2. Department of Anesthesiology and Perioperative Care, University of California San Francisco, San Francisco, Calif;3. Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tenn;1. Oral Maxillofacial Head-Neck Key Laboratory of Medical Biology, and central laboratory of Liaocheng People''s Hospital, Liaocheng, Shandong 252000, China;2. Department of Oral and Maxillofacial Surgery, Liaocheng People''s Hospital, Liaocheng, Shandong 252000, China;3. School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia;1. Brucellosis Research Unit, National Veterinary Research Institute, Vom 930001, Plateau State, Nigeria;2. Division of Infection and Pathway, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK;3. Unidad de Producción y Sanidad Animal, Centro de Investigación y Tecnología Agroalimentaria (CITA), del Gobierno de Aragón, Av. Montañana 930, 50059 Zaragoza, Spain;4. Paris-Est University/Anses, EU/OIE/FAO & National Reference Laboratory for Brucellosis, Animal Health Laboratory, 14 rue Pierre et Marie Curie, 94701 Maisons-Alfort Cedex, France;5. IDISNA—Instituto de Salud Tropical y Depto., Microbiología y Parasitología, Universidad de Navarra, Edificio de Investigación, c/Irunlarrea 1, 31008 Pamplona, Spain;6. Avia-GIS, Risschotlei 33, BE-2980 Zoersel, Belgium;7. Department of Veterinary Public Health and Preventive Medicine, Faculty of Veterinary Medicine, PMB 1096, Ahmadu Bello University, Zaria, Nigeria |
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| 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 μg/ml) inhibited FPAEC proliferation and induced apoptosis under normoxic conditions (21% O2) in vitro. LPS-induced FPAEC apoptosis was attenuated in hypoxia (5% O2) and exacerbated by hyperoxia (55% O2). 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. |
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