Research Papers: Pathology:

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

Gun Yoon, Choong Sik Oh and Hyun-Soo Kim _

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Oncotarget. 2016; 7:33675-33688. https://doi.org/10.18632/oncotarget.9372

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Gun Yoon1, Choong Sik Oh2 and Hyun-Soo Kim3

1 Department of Obstetrics and Gynecology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan-si, Gyeongsangnam-do, Republic of Korea

2 Aerospace Medicine Research Center, Republic of Korea Air Force Aerospace Medical Center, Cheongju-si, Chungcheongbuk-do, Republic of Korea

3 Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

Correspondence to:

Hyun-Soo Kim, email:

Keywords: endothelial nitric oxide synthase, hypoxia-inducible factor-1α, hypergravity, heart, liver, Pathology Section

Received: March 10, 2016 Accepted: May 05, 2016 Published: May 14, 2016


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.

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