Abstract
The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1α protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1α was increased by 1.69±0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1α expression by bilirubin. HIF-1α expression decreased by 10 μM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1α concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1α mRNA expression. In coonclusion, bilirubin enhances HIF-1α transcription as well as the up-regulation of HIF-1α protein translation through the attenuation of ROS and subunits of NADPH oxidase.
| Original language | English |
|---|---|
| Pages (from-to) | S146-S154 |
| Journal | Journal of Korean Medical Science |
| Volume | 29 |
| DOIs | |
| Publication status | Published - 2014 Jan 1 |
| Externally published | Yes |
Fingerprint
Keywords
- Bilirubin
- HIF-1
- Proximal tubular Cell
- ROS
ASJC Scopus subject areas
- Medicine(all)
Cite this
Bilirubin activates transcription of HIF-1α in human proximal tubular cells cultured in the physiologic oxygen content. / Kim, Sung Gyun; Ahn, Shin Young; Lee, Eun Seong; Kim, Sejoong; Na, Ki Young; Chae, Dong Wan; Chin, Ho Jun.
In: Journal of Korean Medical Science, Vol. 29, 01.01.2014, p. S146-S154.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bilirubin activates transcription of HIF-1α in human proximal tubular cells cultured in the physiologic oxygen content
AU - Kim, Sung Gyun
AU - Ahn, Shin Young
AU - Lee, Eun Seong
AU - Kim, Sejoong
AU - Na, Ki Young
AU - Chae, Dong Wan
AU - Chin, Ho Jun
PY - 2014/1/1
Y1 - 2014/1/1
N2 - The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1α protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1α was increased by 1.69±0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1α expression by bilirubin. HIF-1α expression decreased by 10 μM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1α concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1α mRNA expression. In coonclusion, bilirubin enhances HIF-1α transcription as well as the up-regulation of HIF-1α protein translation through the attenuation of ROS and subunits of NADPH oxidase.
AB - The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1α protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1α was increased by 1.69±0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1α expression by bilirubin. HIF-1α expression decreased by 10 μM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1α concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1α mRNA expression. In coonclusion, bilirubin enhances HIF-1α transcription as well as the up-regulation of HIF-1α protein translation through the attenuation of ROS and subunits of NADPH oxidase.
KW - Bilirubin
KW - HIF-1
KW - Proximal tubular Cell
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=84930974947&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930974947&partnerID=8YFLogxK
U2 - 10.3346/jkms.2014.29.S2.S146
DO - 10.3346/jkms.2014.29.S2.S146
M3 - Article
C2 - 25317019
AN - SCOPUS:84930974947
VL - 29
SP - S146-S154
JO - Journal of Korean Medical Science
JF - Journal of Korean Medical Science
SN - 1011-8934
ER -