Document Detail

Downregulation of cell survival signalling pathways and increased cell damage in hydrogen peroxide-treated human renal proximal tubular cells by alpha-erythropoietin.
MedLine Citation:
PMID:  19508320     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Erythropoietin has been shown to have a protective effect in certain models of ischaemia-reperfusion, and in some cases the protection has been correlated with activation of signalling pathways known to play a role in cell survival and proliferation. We have studied whether erythropoietin would overcome direct toxic effects of hydrogen peroxide (H(2)O(2)) treatment to human renal proximal tubular (HK-2) cells. MATERIALS AND METHODS: HK-2 cells were incubated with H(2)O(2) (2 mm) for 2 h with or without erythropoietin at concentrations of 100 and 400 U/ml, and cell viability/proliferation was assessed by chemical reduction of MTT. Changes in phosphorylation state of the kinases Akt, glycogen synthase kinase-3beta (GSK-3beta), mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase 1 and 2 (ERK1/ERK2) were also analysed. RESULTS: Cells incubated with H(2)O(2) alone showed a significant decrease in viability, which did not significantly change by addition of erythropoietin at concentration of 100 U/ml, but was further reduced when concentration of erythropoietin was increased to 400 U/ml. Phosphorylation state of the kinases Akt, GSK-3beta, mTOR and ERK1/ERK2 of H(2)O(2)-treated HK-2 cells was slightly altered in the presence of erythropoietin at concentration of 100 U/ml, but was significantly less in the presence of erythropoietin at a concentration of 400 U/ml. Phosphorylation of forkhead transcription factor FKHRL1 was diminished in cells incubated with H(2)O(2) and erythropoietin at a concentration of 400 U/ml. CONCLUSIONS: Erythropoietin, at high concentrations, may significantly increase cellular damage in HK-2 cells subjected to oxidative stress, which may be due in part to decrease in activation of important signalling pathways involved in cell survival and/or cell proliferation.
M Andreucci; G Fuiano; P Presta; G Lucisano; F Leone; L Fuiano; V Bisesti; P Esposito; D Russo; B Memoli; T Faga; A Michael
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-08
Journal Detail:
Title:  Cell proliferation     Volume:  42     ISSN:  1365-2184     ISO Abbreviation:  Cell Prolif.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-14     Completed Date:  2009-08-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  554-61     Citation Subset:  IM    
Magna Graecia University, Catanzaro, Italy.
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MeSH Terms
Cell Line
Cell Survival / drug effects*
Erythropoietin / pharmacology*
Extracellular Signal-Regulated MAP Kinases / metabolism
Glycogen Synthase Kinase 3 / metabolism
Hydrogen Peroxide / toxicity*
Kidney Tubules, Proximal / cytology*
Oxidative Stress / drug effects
Phosphorylation / drug effects
Protein Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction / drug effects*
Reg. No./Substance:
11096-26-7/Erythropoietin; 7722-84-1/Hydrogen Peroxide; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein; EC Proteins c-akt; EC Signal-Regulated MAP Kinases; EC Synthase Kinase 3

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