IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ERYTHROPOIETIN-INDUCED ENDOTHELIAL CELL MIGRATION RELIES ON AN INTRACELLULAR CALCIUM INCREASE
Autor/es:
CHAMORRO ME; VITTORI D; MALTANERI R; NESSE A; SCHIAPPACASSE A
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Apart from itseffect on the hematopoietic system, erythropoietin (Epo), a glycosylated cytokineproduced by the adult kidney, has also been involved in angiogenesis, a processwith important physiological and pathological implications. Since the mechanismsunderlying such proangiogenic behavior are little understood, it was ourpurpose to study possible effectors of Epo in cultures of the endothelial cellline EA.hy926, with special interest in the comparison with itsnon-hematopoietic carbamylated derivative (cEpo).Calcium (Ca)plays a key role in cell migration, through regulation of focal adhesions andcytoskeleton dynamics. In wound-healing assays, Epo-induced migration (200ng/mL, 15 h) was inhibited by incubation with the Ca2+ chelator EGTA(1 mM) (Control:27±2.0%; *Epo: 35±0.9%; Epo+EGTA: 27±2.1%; *P<0.05, Kruskal Wallis-Dunn,n=7). Epo also generated a transient [Ca2+]i rise (flowcytometry, Fluo4-AM) in EA.hy926 cells within the first 30 seconds ofstimulation, peaking at 7 sec (39±7.1% Epo vs. unstimulated cells, P<0.05, Kruskal Wallis-Dunn; n=4), asdemonstrated for other angiogenic factors. The carbamylated derivative of Epo(cEpo), which has no proangiogenic effect, failed to produce such [Ca2+]irise. The absence of Ca2+ in the resuspension buffer abrogatedthe Epo-induced transient increase in [Ca2+]i, suggestingan extracellular source of the cation. Accordingly, a 15 h-incubation with Eposignificantly increased the expression levels of the TRPC3 calcium channel(flow cytometry: *Epo: 125±12.9; cEpo: 103±8.0 expressed as % of control; *P<0.05,Kruskal Wallis-Dunn, n=5). Moreover, calpain activity appears to be involved inEpo-stimulated migration.Our resultsdemonstrate that Epo induces endothelial migration by affecting Ca homeostasisthrough an increase in Ca influx via modulation of Ca channels. These findings highlightthe importance of intracellular Ca dynamics in angiogenesis, a prime target inthe treatment of different pathologies.