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 language | English |
|---|---|
| Pages (from-to) | 33675-33688 |
| Number of pages | 14 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - 2016 Jun 7 |
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All Science Journal Classification (ASJC) codes
- Oncology
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Distinctive expression patterns of hypoxia-inducible factor-1a and endothelial nitric oxide synthase following hypergravity exposure. / Yoon, Gun; Oh, Choong Sik; Kim, Hyun Soo.
In: Oncotarget, Vol. 7, No. 23, 07.06.2016, p. 33675-33688.Research output: Contribution to journal › Article
TY - JOUR
T1 - Distinctive expression patterns of hypoxia-inducible factor-1a and endothelial nitric oxide synthase following hypergravity exposure
AU - Yoon, Gun
AU - Oh, Choong Sik
AU - Kim, Hyun Soo
PY - 2016/6/7
Y1 - 2016/6/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84973647177&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84973647177&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.9372
DO - 10.18632/oncotarget.9372
M3 - Article
C2 - 27191892
AN - SCOPUS:84973647177
VL - 7
SP - 33675
EP - 33688
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 23
ER -