title: Distinctive expression patterns of hypoxia-inducible factor-1α and endothelial nitric oxide synthase following hypergravity exposure.
abstract: This study was designed to examine the expression of hypoxia-inducible factor-1α (HIF-1α) and the level and activity of endothelial nitric oxide synthase (eNOS) in the hearts and livers of mice exposed to hypergravity. Hypergravity-induced hypoxia and the subsequent post-exposure reoxygenation significantly increased cardiac HIF-1α levels. Furthermore, the levels and activity of cardiac eNOS also showed significant increase immediately following hypergravity exposure and during the reoxygenation period. In contrast, the expression of phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) showed significant elevation only during the reoxygenation period. These data raise the possibility that the increase in cardiac HIF-1α expression induced by reoxygenation involves a cascade of signaling events, including activation of the Akt and ERK pathways. In the liver, HIF-1α expression was significantly increased immediately after hypergravity exposure, indicating that hypergravity exposure to causes hepatocellular hypoxia. The hypergravity-exposed livers showed significantly higher eNOS immunoreactivity than did those of control mice. Consistent with these results, significant increases in eNOS activity and nitrate/nitrite levels were also observed. These findings suggest that hypergravity-induced hypoxia plays a significant role in the upregulation of hepatic eNOS.
authors.affiliation: Department of Obstetrics and Gynecology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan-si, Gyeongsangnam-do, Republic of Korea.
authors.forename: Gun
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Aerospace Medicine Research Center, Republic of Korea Air Force Aerospace Medical Center, Cheongju-si, Chungcheongbuk-do, Republic of Korea.
authors.forename: Choong Sik
authors.initials: CS
authors.lastname: Oh
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D018471:Hypergravity / Q000009:adverse effects*; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: Pathology Section; endothelial nitric oxide synthase; heart; hypergravity; hypoxia-inducible factor-1α; liver