title: Erythropoietin and hypoxia increase erythropoietin receptor and nitric oxide levels in lung microvascular endothelial cells.
abstract: Acute lung exposure to low oxygen results in pulmonary vasoconstriction and redistribution of blood flow. We used human microvascular endothelial cells from lung (HMVEC-L) to study the acute response to oxygen stress. We observed that hypoxia and erythropoietin (EPO) increased erythropoietin receptor (EPOR) gene expression and protein level in HMVEC-L. In addition, EPO dose- and time-dependently stimulated nitric oxide (NO) production. This NO stimulation was evident despite hypoxia induced reduction of endothelial NO synthase (eNOS) gene expression. Western blot of phospho-eNOS (serine1177) and eNOS and was significantly induced by hypoxia but not after EPO treatment. However, iNOS increased at hypoxia and with EPO stimulation compared to normal oxygen tension. In accordance with our previous results of NO induction by EPO at low oxygen tension in human umbilical vein endothelial cells and bone marrow endothelial cells, these results provide further evidence in HMVEC-L for EPO regulation of NO production to modify the effects of hypoxia and cause compensatory vasoconstriction.
authors.affiliation: Institute of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Bojana B
authors.initials: BB
authors.lastname: Beleslin-Čokić
authors.forename: Vladan P
authors.initials: VP
authors.lastname: Cokić
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Barbora
authors.initials: B
authors.lastname: Piknova
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Teng
authors.forename: Alan N
authors.initials: AN
authors.lastname: Schechter
authors.forename: Constance T
authors.initials: CT
authors.lastname: Noguchi
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000098:blood supply*; D055806:Microvessels / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009566:Nitrates; D009573:Nitrites; D004921:Erythropoietin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase