The distinct erythropoietin functions that promote cell survival and proliferation are affected by aluminum exposure through mechanisms involving erythropoietin receptor

VITTORI DANIELA; PREGI NICOLÁS; PÉREZ GLADYS; GARBOSSA GRACIELA; NESSE ALCIRA

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Elsevier

Año: 2005 vol. 1743 p. 29 - 36

0167-4889

Erythropoietin (Epo) promotes the development of erythroid progenitors by triggering intracellular signals through the binding to itsspecific receptor (EpoR). Previous results related to the action of aluminum (Al) on erythropoiesis let us suggest that the metal affects Epointeraction with its target cells. In order to investigate this effect on cell activation by the Epo–EpoR complex, two human cell lines withdifferent dependence on Epo were subjected to Al exposure. In the Epo-independent K562 cells, Al inhibited Epo antiapoptotic action andtriggered a simultaneous decrease in protein and mRNA EpoR levels. On the other hand, proliferation of the strongly Epo-dependent UT-7cells was enhanced by long-term Al treatment, in agreement with the upregulation of EpoR expression during Epo starvation. Results providesome clues to the way by which Epo supports cell survival and growth, and demonstrate that not all the intracellular factors needed toguarantee the different signaling pathways of Epo-cell activation are available or activated in cells expressing EpoR. This study then suggeststhat at least one of the mechanisms by which Al interfere with erythropoiesis might involve EpoR modulation.