RGD Reference Report - Role of serum and glucocorticoid-regulated kinase-1 in the protective effects of erythropoietin during renal ischemia/reperfusion injury. - Rat Genome Database

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

Authors: Rusai, K  Prokai, A  Szebeni, B  Fekete, A  Treszl, A  Vannay, A  Muller, V  Reusz, G  Heemann, U  Lutz, J  Tulassay, T  Szabo, AJ 
Citation: Rusai K, etal., Biochem Pharmacol. 2010 Apr 15;79(8):1173-81. doi: 10.1016/j.bcp.2009.11.022. Epub 2009 Dec 2.
RGD ID: 10401077
Pubmed: PMID:19961832   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bcp.2009.11.022   (Journal Full-text)

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 16h hypoxia. Incubation with EPO at a doses of 400U/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 500U/kg EPO 24h prior to ischemia. EPO resulted in less severe tissue injury and ameliorated the elevation in creatinine and urea nitrogen levels 24h 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Kidney Reperfusion Injury treatmentIDA 10401077 RGD 
Kidney Reperfusion Injury treatmentISOEPO (Homo sapiens)10401077; 10401077 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Epo  (erythropoietin)

Genes (Mus musculus)
Epo  (erythropoietin)

Genes (Homo sapiens)
EPO  (erythropoietin)


Additional Information