Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress.

Abstract

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 H(2)O(2). 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.

• Authors: Pisut Katavetin, Reiko Inagi, Toshio Miyata, Jing Shao, Ryoji Sassa, Stephen Adler, Nobuaki Eto, Hideki Kato, Toshiro Fujita, Masaomi Nangaku
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 359 Issue 4 Pg. 928-34 (Aug 10 2007) ISSN: 0006-291X [Print] United States
• PMID: 17560935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Erythropoietin
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat

Topics

• Animals
• Cells, Cultured
• Dose-Response Relationship, Drug
• Endothelial Cells (cytology, drug effects, physiology)
• Erythropoietin (administration & dosage)
• Gene Expression Regulation, Enzymologic (drug effects, physiology)
• Heme Oxygenase (Decyclizing) (metabolism)
• Kidney Diseases (drug therapy, pathology)
• Male
• Oxidative Stress (drug effects, physiology)
• Rats
• Rats, Inbred Dahl
• Treatment Outcome