Bilirubin activates transcription of HIF-1α in human proximal tubular cells cultured in the physiologic oxygen content

Sung Gyun Kim, Shin Young Ahn, Eun Seong Lee, Sejoong Kim, Ki Young Na, Dong Wan Chae, Ho Jun Chin

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)S146-S154
JournalJournal of Korean Medical Science
Volume29
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

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Hypoxia-Inducible Factor 1
Bilirubin
Cultured Cells
Oxygen
Reactive Oxygen Species
Phosphatidylinositol 3-Kinases
Gene Knockdown Techniques
Kidney
Cell Hypoxia
Messenger RNA
NADPH Oxidase
Protein Biosynthesis
Hydrogen Peroxide
Small Interfering RNA
Phosphotransferases
Up-Regulation
Phosphorylation

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 journalArticle

Kim, Sung Gyun ; Ahn, Shin Young ; Lee, Eun Seong ; Kim, Sejoong ; Na, Ki Young ; Chae, Dong Wan ; Chin, Ho Jun. / Bilirubin activates transcription of HIF-1α in human proximal tubular cells cultured in the physiologic oxygen content. In: Journal of Korean Medical Science. 2014 ; Vol. 29. pp. S146-S154.
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