| Downregulation of cell survival signalling pathways and increased cell damage in hydrogen peroxide-treated human renal proximal tubular cells by alpha-erythropoietin. | |
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MedLine Citation:
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PMID: 19508320 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-08 |
Journal Detail:
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Title: Cell proliferation Volume: 42 ISSN: 1365-2184 ISO Abbreviation: Cell Prolif. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-14 Completed Date: 2009-08-03 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9105195 Medline TA: Cell Prolif Country: England |
Other Details:
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Languages: eng Pagination: 554-61 Citation Subset: IM |
Affiliation:
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Magna Graecia University, Catanzaro, Italy. andreucci@unicz.it |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Cell Survival / drug effects* Erythropoietin / pharmacology* Extracellular Signal-Regulated MAP Kinases / metabolism Glycogen Synthase Kinase 3 / metabolism Humans 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* |
| Chemical | |
Reg. No./Substance:
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11096-26-7/Erythropoietin; 7722-84-1/Hydrogen Peroxide; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.26/Glycogen Synthase Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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