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Downregulation of cell survival signalling pathways and increased cell damage in hydrogen peroxide-treated human renal proximal tubular cells by alpha-erythropoietin.

Abstract：

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.

journal_name

Cell Prolif

journal_title

Cell proliferation

authors

Andreucci M,Fuiano G,Presta P,Lucisano G,Leone F,Fuiano L,Bisesti V,Esposito P,Russo D,Memoli B,Faga T,Michael A

doi

10.1111/j.1365-2184.2009.00617.x

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

554-61

issue

eissn

0960-7722

issn

1365-2184

pii

CPR617

journal_volume

pub_type

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Downregulation of cell survival signalling pathways and increased cell damage in hydrogen peroxide-treated human renal proximal tubular cells by alpha-erythropoietin.