Effects of cell proliferation, protein synthesis and intra-cellular signal transduction

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In patients with chronic renal failure, recombinant human erythropoietin (rHuEpo) improves renal anemia. However, rHuEpo induced-hypertension occurs commonly (about 30%). The aim of this study was to assess the relation of rHuEpo to cell proliferation, protein synthesis and cytosolic free calcium ([Ca^<2+>] i).We investigated whether rHuEpo induce cell proliferation and protein synthesis in cultured smooth muscle cells or not. Smooth muscle cells were incubated with various concentration of rHuEpo (0,0.1,5,50U/ml). RHuEpo induced DNA and protein synthesis measured by ^3H-thymidine and ^3H-leucine in dose dependent manner.We tried to measure the erythropoietin receptor by binding assay using ^<125>I-rHuEpo, but failed. In 1996, Ammarguellat reported that northern blot analysis revealed the expression of Epo receptor messenger RNA in smooth muscle cells of rats.We also investigated [Ca^<2+>] i in platelets using fluorescent indicator quin 2 in patients with chronic renal failure. Resting [Ca^<2+>] i was higher in patients with chronic renal failure than in controls. RHuEpo (40U/ml) increased [Ca^<2+>] i in platelets in both chronic renal failure and controls. However, the increase in [Ca^<2+>] i in platelets was higher in chronic renal failure than that in controls. There was a positive relationship between changes in [Ca^<2+>] i in platelets and mean blood pressure ((r=0.56, p<0.05).It is suggested that rHuEpo induce cell proliferation and protein synthesis and increase intracellar free calcium, which may attribute to rHuEpo-induced hypertension in part.