We compared the in vivo plasma clearance and organ accumulation in anesthetized rats of 125I-labeled, recombinant human erythropoietin and 125I-labeled, desialylated recombinant erythropoietin. The immediate volume of distribution of 125I-labeled, recombinant erythropoietin approximated that of the plasma volume. Its plasma clearance was multiexponential, with an initial rapid distribution phas...

More than 30 years ago the kidney in adult mammals was found to be an essential component of a regulatory feedback loop that controls the number of red blood cells and thereby the oxygen capacity of the blood. The kidney releases a hormone, erythropoietin, that stimulates erythrocyte formation in the bone marrow (26). The rate of release of erythropoietin from the kidney is greatly enhanced by ...

Erythropoietin and its receptor function as primary mediators of the normal physiological response to hypoxia. Erythropoietin is recognized for its central role in erythropoiesis, but studies in which recombinant human erythropoietin (epoetin alfa) is injected directly into ischaemic rodent brain show that erythropoietin also mediates neuroprotection. Abundant expression of the erythropoietin r...

Both the endogenous plasma erythropoietin levels and the rate of plasma clearance of injected erythropoietin have been investigated in SJL/J mice that had been rendered leukemic by the injection of Rauscher virus. The results show an elevated level of endogenous erythropoietin coupled with an accelerated rate of erythropoietin clearance. These re sults are inconsistent with the hypothesis previ...

Adaptive responses to hypoxia occur in many biological systems. A well-characterized example is the hypoxic induction of the synthesis of erythropoietin, a hormone which regulates erythropoiesis and hence blood oxygen content. The restricted expression of the erythropoietin gene in subsets of cells within kidney and liver has suggested that this specific oxygen-sensing mechanism is restricted t...

Anemia linked to a relative deficiency of renal erythropoietin production is a significant cause of morbidity and medical expenditures in the developed world. Recombinant erythropoietin is expensive and has been linked to excess cardiovascular events. Moreover, some patients become refractory to erythropoietin because of increased production of factors such as hepcidin. During fetal life, the l...

Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 2002; 8: 495–505 29. Parsa CJ, Matsumoto A, Kim J et al. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 2003; 112: 999–1007 30. Yang CW, Li C, Jung JY et al. Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney. FASEB J 2003; 17: 17...

Anemia of cancer and chronic inflammatory diseases is a frequent complication affecting quality of life. For cancer patients it represents a particularly bad prognostic. Low level of erythropoietin is considered as one of the causes of anemia in these pathologies. The deficiency in erythropoietin production results from pro-inflammatory cytokines effect. However, few data is available concernin...

Gene therapy holds a major promise. However, until now, this promise was fulfilled only in few cases, in rare genetic diseases. One very common clinical condition is anemia. Patients with anemia of chronic renal failure are treated with erythropoietin. The objective of this study was to develop a therapeutic platform for serum-secreted proteins like erythropoietin. We developed a tissue protein...

The murine erythroleukemia (MEL) cell line, TSA8, becomes responsive to erythropoietin after induction with dimethyl sulfoxide (DMSO). We examined the signalling pathways involved in the commitment of TSA8 cells to become the erythroid progenitor cells responsive to erythropoietin, comparing them with the pathway used in an erythropoietin-induced change of the progenitor cells. Amiloride, an in...