ACTION OF MODIFIED ERYTHROPOIETINS ON ENDOTHELIAL CELLS IN A PROINFLAMMATORY ENVIRONMENT

MALTANERI, R.; VITTORI, D.; SCHIAVINATTO, D.; NESSE, A.; CHAMORRO, MARÍA E.; SCHIAPPACASSE, AGUSTINA

Ciudad Autonoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias. LXII Reunión Anual de la Sociedad Argentina de Investigaciones Clínicas; 2017

Erythropoietin (Epo), the erythropoiesis growthfactor, is also known as an antiapoptotic agent. In this context, carbamylated Epo(cEpo) maintains the neuroprotective effect but fails to stimulateerythropoiesis. Despite the benefit of Epo treatment to overcome anemiaassociated to different pathologies, a significant number of patients,particularly those with cardiovascular or chronic renal diseases, fail torespond. This may be related to the simultaneous presence of other independentrisk factors, such as hyperhomocysteinemia. This study was aimed at identifyingEpo structural changes due to carbamylation and N-homocysteinylation, and investigating whether these changes couldaffect Epo activity on EA.hy926 endothelial cells in a proinflammatoryenvironment. cEpo was prepared by reaction with potassium cyanatewhile homocysteine thiolactone was incubated with Epo to yield the N-homocysteinylated protein. Analysis bygel and capillary electrophoresis revealed structural changes with respect tothe native protein. Wound healing assays showed a stimulatory effect of TNF-αon cell migration which was significantly increased by TNF-α+Epo combination (C21±2%, *TNF-α 44±3%, Epo 30±2%, *EpoTNF-α 66±4%, *P