DIFFERENTIAL EFFECTS OF ERYTHROPOIETIN AND CARBAMYLATED ERYTHROPOIETIN ON ENDOTHELIAL CELL MIGRATION

MALTANERI R; CHAMORRO ME; SCHIAPPACASSE A; NESSE A; VITTORI D

INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND CELLULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2017 vol. 85 p. 25 - 34

1357-2725

Erythropoietin(Epo) has long been recognized for its effects beyond the hematopoietic system,including cytoprotection against apoptosis and oxidative damage. Such activity has raised interest in potential therapeutic uses of Epo besides anemia treatment, but also concern about the possibility of unwanted targets of its action. In order to overcome possible side effects of Epo, several derivatives are currently under study. Among them is the non-erythopoietic carbamylated erythropoietin (cEpo), which retains the cytoprotective activity of Epo. In endothelial cells, Epo has been reported to act as a proangiogenic factor, but the effects of cEpo are less certain. In the present work, we found that Epo, unlike cEpo, stimulates proliferation and migration of the endothelial cell line EA.hy926. Such promigratory behavior of Epo seems to be mediated by its classical homodimeric receptor and signaling through JAK and PI3K. Moreover, Epo-induced endothelial migration seems to rely on the generation of nitric oxide and an increase of cytosolic calcium through TRPC3 membrane channels. Despite its lack of promigratory activity, cEpo reduced the burden of ROS in cells exposed to hydrogen peroxide, thus sharing the antioxidant effect of Epo. The differential effect of both erythropoietins in endothelial cell migration seems to depend on an early termination of the cEpo signal by the phosphatase PTP1B, as seen in erythroid cell cultures. Our results provide new insight into the effects of Epo and cEpo on endothelial cells, particularly into the mechanisms underlying their differential promigratory action.