Erythropoietin oxidation

Antibodies directed against recombinant erythropoietin have been obtained from rabbits immunized with the hormone and Freunds complete adjuvant [64], Two sets of antibodies are present in the serum of rabbits that have been immunized, Fig. (3C). The results of oxidation of the erythropoietin with periodate, Fig. (25A), reaction of the antibodies with lectins of known carbohydrate specificity, Fig. (25B) and inhibition of the antibodies with the structural monosaccharide residues of the hormone, Fig. (26), have established the types of antibodies to be anti-carbohydrate antibodies and the immunodeterminants for these antibodies are oligosaccharides with the following structure N-acetyl neuraminyl a(2->3)... 

Fig. (25). Periodate oxidation (A) and reaction with lectins (B) of anti-erythropoietin antibodies (S), EO, E2, E8= hrs of oxidation, LI = Maackia, L2 = Sambucus.

Control of heme biosynthesis revolves around the initial enzyme, ALA-synthase. Heme, the end product of this pathway, exerts an inhibitory effect on ALA-synthase through several mechanisms. Heme, or its oxidation product hematin, activates a repressor protein that turns off ALA-synthase biosynthesis at the translation level. Erythropoietin, a protein produced by the kidneys and found in larger than normal amounts in high-altitude dwellers, counteracts the effects of the repressor protein. Erythropoietin deficiency exists in chronic kid-... 

Poux JM, Lartigue M, Chaisemartin RA et al. (1995) Uraemia is necessary for erythropoietin-induced hypertension in rats. Clin Exp Pharmacol Physiol 22 769-771 Roczniak A, Fryer JN, Levine DZ, Burns KD (1999) Downregulation of neuronal nitric oxide synthase in the rat remnant kidney. J Am Soc Nephrol 10 704-713 Santos F, Chan JCM, Hanna JDetal. (1992) The effect of growth hormone on the growth failure of chronic renal failure. Pe-diatr Nephrol 6 262-266... 

Nemeth, S. Turi, I. Haszon and B. Bereczki, Vitamin E Alleviates the Oxidative Stress of Erythropoietin in Uremic Children on Hemodialysis, Pediatric Nephrology 14(2000) 13-17. 

Hemosol (Canada) Oxidized raffinose-polymerized and cross-linked human Hb (o-Raff-Hbor Hemolink) Orthopedic or cardiac surgery use as an adjunct to erythropoietin in treatment of chronic renal failure... 

G. Calapai, M. C. Marciano, F. Corica, A. Allegra, A. Parisi, N. Frisina, A. P. Caputi, M. Buemi, Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation, Eur J Pharmacol 401, 349-56(2000). 

Hypoxia is an integral part of ischemia and plays a vital role in its pathophysiology. Hypoxia inducible factor (HIF-1) mediates transcription of several genes. Activation of HIF-1 also stimulates the production of VEGF, erythropoietin, bFGF, and other factors associated with neovascularization (Semenza, 2000 Maxwell and RatcHffe, 2002 Vincent et al., 2002). Another potential factor for neovascularization is adenosine, a neuromodulator that can act on specific receptors (putatively A2A and A2B receptors) on the endothelial cells, and through nitric oxide mediation it can stimulate cell migration and tube formation (Lutty and Mcleod, 2003). 

Results obtained" from the reaction of periodate with oligosaccharide structures in erythropoietin are consistent with the proposal that antibodies directed against the recombinant hormone are anti-carbohydrate . That oligosaccharide sequences are involved in the binding of human spermatozoa to a glycoprotein of the zona pellucida, is indicated " " by a marked decrease in binding that accompanies selective periodate oxidation of terminal sialic acid residues of the glycoprotein. 

Zaman K, Ryu H, HaU D, 0 Donovan K, Lin Kl, Miller MR Marquis JC, Baraban JM, Semenza GL, Ratan RR (1999) Protection from oxidative stress-induced apoptosis in cortical neuronal cultures by iron chelators is associated with enhanced DNA binding of hypoxia-inducible factor-1 and ATF-l/CREB and increased expression of glycolytic enzymes, p21(wafl/cipl), and erythropoietin. J Neurosci 19 9821-9830... 

It had long been noted that many patients with autonomic failure may also be anemic. Hoeldtke and Streeten published a landmark study demonstrating that erythropoietin given via subcutaneous injection could cause significant elevations in blood pressure and increasing blood counts (86). Subsequent studies have suggested that these effects are independent of each other and that erythropoietin possesses direct vasoconstrictive effects related to its effects on peripheral nitric oxide (87,88). 

Epinephrine, see Adrenaline Erythromycin, versus the new macrohdes, 21.269 Erythropoietin, pure red cell aplasia, 27.348 status and safety, 16.400 Ethambutol, optic neuropathy, 30.358 Ethylene oxide, dialyser hypersensitivity,... 

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