Role of serum and glucocorticoid-regulated kinase-1 in the protective effects of erythropoietin during renal ischemia/reperfusion injury

Krisztina Rusai, Ágnes Prókai, Beáta Szebeni, Andrea Fekete, András Treszl, Ádám Vannay, Veronika Müller, György Reusz, Uwe Heemann, Jens Lutz, Tivadar Tulassay, Attila J. Szabó

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Erythropoietin (EPO) protects the kidneys from ischemia/reperfusion (I/R) injury; however, the exact signalling mechanisms are not fully understood. The serum and glucocorticoid-regulated kinase 1 (SGK1) is an anti-apoptotic protein kinase regulated through the phosphatidylinositol 3-kinase (PI3-kinase) pathway by cellular stimuli, hormones and growth factors. The objective of the present study was to examine the role of SGK1 in the renoprotective effects of EPO in renal I/R injury.In vitro, cultures of HEK293 cells were exposed to 16 h hypoxia. Incubation with EPO at a doses of 400 U/ml exerted a protective effect on cell death assessed by LDH release and Annexin V FACS analysis. This was paralleled by up-regulation of SGK1 expression, as well as phosphorylation. Downregulation of SGK1 expression by small interfering RNA technique ameliorated the anti-apoptotic effect of EPO treatment.In an in vivo rat model of unilateral renal I/R injury, rats were treated with 500 U/kg EPO 24 h prior to ischemia. EPO resulted in less severe tissue injury and ameliorated the elevation in creatinine and urea nitrogen levels 24 h after reperfusion. Furthermore, SGK1 expression and phosphorylation were higher in EPO compared to vehicle-treated rats as demonstrated by real-time PCR, Western blot and immunofluorescence technique.We conclude that EPO protects from renal I/R injury and SGK1 might contribute to the mediation of EPO effects under ischemic conditions.

Original languageEnglish
Pages (from-to)1173-1181
Number of pages9
JournalBiochemical Pharmacology
Volume79
Issue number8
DOIs
Publication statusPublished - Apr 1 2010

Keywords

  • Apoptosis
  • EPO
  • Hypoxia
  • Ischemia/reperfusion
  • Kidney
  • SGK1

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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