Hypoxia-Inducible Factor Activation Protects the Kidney from Gentamicin-Induced Acute Injury

Jeong myung Ahn, Sun Jin You, Yun Mi Lee, Se Won Oh, Shin Young Ahn, Sejoong Kim, Ho Jun Chin, Dong Wan Chae, Ki Young Na

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Gentamicin nephrotoxicity is one of the most common causes of acute kidney injury (AKI). Hypoxia-inducible factor (HIF) is effective in protecting the kidney from ischemic and toxic injury. Increased expression of HIF-1α mRNA has been reported in rats with gentamicin-induced renal injury. We hypothesizd that we could study the role of HIF in gentamicin-induced AKI by modulating HIF activity. In this study, we investigated whether HIF activation had protective effects on gentamicin-induced renal tubule cell injury. Gentamicin-induced AKI was established in male Sprague-Dawley rats. Cobalt was continuously infused into the rats to activate HIF. HK-2 cells were pre-treated with cobalt or dimethyloxalylglycine (DMOG) to activate HIF and were then exposed to gentamicin. Cobalt or DMOG significantly increased HIF-1α expression in rat kidneys and HK-2 cells. In HK-2 cells, HIF inhibited gentamicin-induced reactive oxygen species (ROS) formation. HIF also protected these cells from apoptosis by reducing caspase-3 activity and the amount of cleaved caspase-3, and -9 proteins. Increased expression of HIF-1α reduced the number of gentamicin-induced apoptotic cells in rat kidneys and HK-2 cells. HIF activation improved the creatinine clearance and proteinuria in gentamicin-induced AKI. HIF activation also ameliorated the extent of histologic injury and reduced macrophage infiltration into the tubulointerstitium. In gentamicin-induced AKI, the activation of HIF by cobalt or DMOG attenuated renal dysfunction, proteinuria, and structural damage through a reduction of oxidative stress, inflammation, and apoptosis in renal tubular epithelial cells.

Original languageEnglish
Article numbere48952
JournalPLoS One
Volume7
Issue number11
DOIs
Publication statusPublished - 2012 Nov 8
Externally publishedYes

Fingerprint

gentamicin
Gentamicins
hypoxia
Chemical activation
kidneys
Kidney
Wounds and Injuries
Acute Kidney Injury
Rats
Cobalt
Hypoxia-Inducible Factor 1
cobalt
rats
cells
Proteinuria
caspase-3
Caspase 3
Hypoxia
apoptosis
Apoptosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hypoxia-Inducible Factor Activation Protects the Kidney from Gentamicin-Induced Acute Injury. / Ahn, Jeong myung; You, Sun Jin; Lee, Yun Mi; Oh, Se Won; Ahn, Shin Young; Kim, Sejoong; Chin, Ho Jun; Chae, Dong Wan; Na, Ki Young.

In: PLoS One, Vol. 7, No. 11, e48952, 08.11.2012.

Research output: Contribution to journalArticle

Ahn, Jeong myung ; You, Sun Jin ; Lee, Yun Mi ; Oh, Se Won ; Ahn, Shin Young ; Kim, Sejoong ; Chin, Ho Jun ; Chae, Dong Wan ; Na, Ki Young. / Hypoxia-Inducible Factor Activation Protects the Kidney from Gentamicin-Induced Acute Injury. In: PLoS One. 2012 ; Vol. 7, No. 11.
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