10.3324/haematol.2013.090076

Resveratrol accelerates erythroid maturation by activation of FoxO3 and ameliorates anemia in beta-thalassemic mice

Abstract

Resveratrol has received increased attention in the last decade due to its wide range of biological activities. \u3b2-thalassemias are worldwide distributed inherited red cell disorders characterized by ineffective-erythropoiesis and red cell oxidative damage with reduced survival. Here, we evaluated the effects of low-dose-resveratrol, a polyphenolic-stilbene, on in vitro human erythroid differentiation of CD34+ from normal and \u3b2-thalassemic subjects. We found that resveratrol induces accelerated erythroid-maturation with accumulation of cells in S-phase of cell-cycle and up-regulation of p21-cyclin-kinase-inhibitor. In sorted colony-forming-units of erythroid cells resveratrol activates Forkhead-box-class-O3, decreases Akt activity and up-regulates anti-oxidant enzymes as catalase. In an in vivo murine model for \u3b2-thalassemia resveratrol (2.4 mg/Kg) reduces ineffective-erythropoiesis, increases hemoglobin-levels, reduces reticulocyte count, ameliorates red cell survival. In both wild-type and \u3b2-thalassemic mice resveratrol up-regulates scavenging enzymes (catalase and peroxiredoxin-2) through Forkhead-box-class-O3 activation. These data indicate that resveratrol inhibits Akt resulting in FoxO3 activation with up-regulation of cytoprotective systems enabling the pathological erythroid-precursors to resist the oxidative-damage and continue to differentiate. The effects of resveratrol on erythropoiesis combined with an amelioration of oxidative stress in circulating red cells validate the use of resveratrol as possible therapeutic strategy in \u3b2-thalassemia

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This paper was published in Catalogo dei prodotti della ricerca.

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