Erythropoietin increases expression and function of vascular copper- and zinc-containing superoxide dismutase.
Previous studies have shown that treatment with erythropoietin (EPO) exerts vascular protective effects. The exact mechanisms responsible for these effects are not completely understood. In the present study, we hypothesized that EPO stimulates expression and activity of copper- and zinc-containing superoxide dismutase (SOD1), thus protecting vascular tissue from oxidative stress induced by excessive concentrations of superoxide anions. EPO treatment of wild-type mice for 2 weeks (1000 U/kg, SC, biweekly) significantly increased aortic expression of SOD1. This effect resulted in a significant reduction of superoxide anion concentrations in aorta of treated mice. The ability of EPO to reduce vascular production of superoxide anions was abolished in SOD1-deficient mice. In a mouse model of wire-induced injury of the common carotid artery, treatment of wild-type mice with EPO prevented pathological remodeling, whereas the vascular effect of EPO was absent in SOD1-deficient mice. Our findings demonstrate that treatment with EPO increases vascular expression of SOD1. This effect appears to be an important molecular mechanism underlying vascular protection by EPO.
d'Uscio
Livius V
LV
Departmentsof Anesthesiology and Molecular Pharmacology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Smith
Leslie A
LA
Katusic
Zvonimir S
ZS
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D004921:Erythropoietin; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt