红细胞生成素受体3.doc

The distinct erythropoietin functions that promote cell survival and proliferation are affected by aluminum exposure through mechanisms involving erythropoietin receptor Daniela Vittori, , Nicolás Pregi, Gladys Pérez, Graciela Garbossa and Alcira Nesse Laboratorio de Análisis Biológicos, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, Piso 4, Ciudad Universitaria, Ciudad de Buenos Aires (C1428EHA), Argentina Received 5 March 2004;? revised 23 July 2004;? accepted 6 August 2004.? Available online 21 August 2004. Abstract Erythropoietin (Epo) promotes the development of erythroid progenitors by triggering intracellular signals through the binding to its specific receptor (EpoR). Previous results related to the action of aluminum (Al) on erythropoiesis let us suggest that the metal affects Epo interaction with its target cells. In order to investigate this effect on cell activation by the Epo–EpoR complex, two human cell lines with different dependence on Epo were subjected to Al exposure. In the Epo-independent K562 cells, Al inhibited Epo antiapoptotic action and triggered a simultaneous decrease in protein and mRNA EpoR levels. On the other hand, proliferation of the strongly Epo-dependent UT-7 cells was enhanced by long-term Al treatment, in agreement with the upregulation of EpoR expression during Epo starvation. Results provide some clues to the way by which Epo supports cell survival and growth, and demonstrate that not all the intracellular factors needed to guarantee the different signaling pathways of Epo-cell activation are available or activated in cells expressing EpoR. This study then suggests that at least one of the mechanisms by which Al interfere with erythropoiesis might involve EpoR modulation. Keywords: Erythropoietin; Aluminum; Erythropoietin receptor; K562 cell; UT-7 cell line; Apoptosis Article Outline 1. Introduction 2. Materials and methods 2.1. Materials 2.2. Ce