Distinctive expression patterns of hypoxia-inducible factor-1a and endothelial nitric oxide synthase following hypergravity exposure

Gun Yoon, Choong Sik Oh, Hyun Soo Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

This study was designed to examine the expression of hypoxia-inducible factor-1a (HIF-1a) 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-1a 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-1a expression induced by reoxygenation involves a cascade of signaling events, including activation of the Akt and ERK pathways. In the liver, HIF-1a 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.

Original languageEnglish
Pages (from-to)33675-33688
Number of pages14
JournalOncotarget
Volume7
Issue number23
DOIs
Publication statusPublished - 2016 Jun 7

All Science Journal Classification (ASJC) codes

  • Oncology

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