TY - JOUR
T1 - Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress
AU - Katavetin, Pisut
AU - Inagi, Reiko
AU - Miyata, Toshio
AU - Shao, Jing
AU - Sassa, Ryoji
AU - Adler, Stephen
AU - Eto, Nobuaki
AU - Kato, Hideki
AU - Fujita, Toshiro
AU - Nangaku, Masaomi
N1 - Funding Information:
This work was supported by research the Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (17390228 to M.N. and 19590939 to R.I.). We are grateful to Professor Kriang Tungsanga (Chulalongkorn University, Bangkok, Thailand) for his support.
PY - 2007/8/10
Y1 - 2007/8/10
N2 - Recent studies have established that erythropoietin (EPO) is a pleiotropic cytokine. In this study we investigated whether pleiotropic effects of EPO may involve regulation of heme oxygenase (HO)-1, an anti-oxidative stress protein. A stimulatory effect of EPO on HO-1 expression was demonstrated in cultured renal endothelial cells, in which EPO decreased intracellular oxidative stress and provided cytoprotection against H2O2. These beneficial effects were partially reversed by a HO-1 inhibitor. We then evaluated whether EPO induces HO-1 and ameliorates renal injury in vivo. Administration of EPO to Dahl salt-sensitive (DS) rats with low salt diet, a model of chronic tubulointerstitial injury, reduced proteinuria, and renal injury including peritubular capillaries rarefaction as compared to vehicle-treated DS rats. This renoprotection was associated with up-regulation of HO-1 in the kidney. In conclusion, EPO-induced HO-1 expression is likely to provide cytoprotection against oxidative stress.
AB - Recent studies have established that erythropoietin (EPO) is a pleiotropic cytokine. In this study we investigated whether pleiotropic effects of EPO may involve regulation of heme oxygenase (HO)-1, an anti-oxidative stress protein. A stimulatory effect of EPO on HO-1 expression was demonstrated in cultured renal endothelial cells, in which EPO decreased intracellular oxidative stress and provided cytoprotection against H2O2. These beneficial effects were partially reversed by a HO-1 inhibitor. We then evaluated whether EPO induces HO-1 and ameliorates renal injury in vivo. Administration of EPO to Dahl salt-sensitive (DS) rats with low salt diet, a model of chronic tubulointerstitial injury, reduced proteinuria, and renal injury including peritubular capillaries rarefaction as compared to vehicle-treated DS rats. This renoprotection was associated with up-regulation of HO-1 in the kidney. In conclusion, EPO-induced HO-1 expression is likely to provide cytoprotection against oxidative stress.
KW - Chronic tubulointerstitial injury
KW - Intracellular reactive oxygen species
KW - Renal endothelial cells
KW - Renoprotection
UR - http://www.scopus.com/inward/record.url?scp=34250630084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250630084&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.05.207
DO - 10.1016/j.bbrc.2007.05.207
M3 - Article
C2 - 17560935
AN - SCOPUS:34250630084
SN - 0006-291X
VL - 359
SP - 928
EP - 934
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -