The distinct erythropoietin functions that promote cell survival and proliferation are affected by aluminum exposure through mechanisms involving erythropoietin receptor.
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.
Vittori
Daniela
D
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. dvittori@qb.fcen.uba.ar
Pregi
Nicolás
N
Pérez
Gladys
G
Garbossa
Graciela
G
Nesse
Alcira
A
D000535:Aluminum / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D020014:K562 Cells; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000737:chemistry / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D000535:Aluminum