SCOPUS: er.jinfo:eu-repo/semantics/publishe

Arnould, Thierry

Caesens-Koenig, Ludmilla

Calay, Damien

Mattart, Laurine

Michiels, Carine

Raes, Martine

Roebroek, Laura

Simon, Dorothy

Tevel, Virginie

Van Steenbrugge, Martine

Zouaoui Boudjeltia, Karim

Endothelial dysfunction is associated with the formation of peroxynitrite, described to be toxic. Recent data also suggests that peroxynitrite is able to activate the protective Nrf2 pathway and/or the unfolded protein response (UPR). The aim of our work was to study the response of human endothelial cells to 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, and to highlight the possible protective roles of Nrf2 or the UPR pathway in this response.Immortal and primary human umbilical vein endothelial cells were exposed to SIN-1. SIN-1 incubation led to Nrf2 activation and to the overexpression of Nrf2-regulated genes, heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1. We also demonstrated that this defensive response protected cells against cell death induced by serum starvation, by reducing apoptosis (monitored by caspase-3 activity and DNA fragmentation) and favoring autophagosome formation, as evidenced by LC3-II accumulation. Interestingly, we observed an activation of the UPR, with a rapid and significant overexpression of CHOP in serum starved cells stimulated with SIN-1. While siRNA mediated knockdown of CHOP had no effect on DNA fragmentation, the invalidation of Nrf2 or HO-1 by siRNA strongly increased DNA fragmentation, but also reinforced the SIN-1-induced LC3-II accumulation.This study shows that peroxynitrite, at least at sublethal concentrations and within a narrow concentration range, could exert protective effects on endothelial cells by modulating the balance between autophagy and apoptosis, through Nrf2-dependent pathways

Mattart, L.

Calay, D.

Roebroeck, L.

Caesens-Koenig, L.

Van Steenbrugge, M.

Tevel, V.

Michiels, C.

Arnould, T.

Boudjeltia, K.Z.

Raes, M.

Repository of the University of Namur

The peroxynitrite donor 3-morpholinosydnonimine activates Nrf2 and the UPR leading to a cytoprotective response in endothelial cells

Roebroek, L.

Erratum to "The peroxynitrite donor 3-morpholinosydnonimine activates Nrf2 and the UPR leading to a cytoprotective response in endothelial cells" [Cell. Signal. 24 (2012) 199-213]

Endothelial dysfunction is associated with the formation of peroxynitrite, described to be toxic. Recent data also suggests that peroxynitrite is able to activate the protective Nrf2 pathway and/or the unfolded protein response (UPR). The aim of our work was to study the response of human endothelial cells to 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, and to highlight the possible protective roles of Nrf2 or the UPR pathway in this response. Immortal and primary human umbilical vein endothelial cells were exposed to SIN-1. SIN-1 incubation led to Nrf2 activation and to the overexpression of Nrf2-regulated genes, heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1. We also demonstrated that this defensive response protected cells against cell death induced by serum starvation, by reducing apoptosis (monitored by caspase-3 activity and DNA fragmentation) and favoring autophagosome formation, as evidenced by LC3-II accumulation. Interestingly, we observed an activation of the UPR, with a rapid and significant overexpression of CHOP in serum starved cells stimulated with SIN-1. While siRNA mediated knockdown of CHOP had no effect on DNA fragmentation, the invalidation of Nrf2 or HO-1 by siRNA strongly increased DNA fragmentation, but also reinforced the SIN-1-induced LC3-II accumulation. This study shows that peroxynitrite, at least at sublethal concentrations and within a narrow concentration range, could exert protective effects on endothelial cells by modulating the balance between autophagy and apoptosis, through Nrf2-dependent pathways.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Michiels, Christiane

DI-fusion

The peroxynitrite donor 3-morpholinosydnonimine activates Nrf2 and the UPR leading to a cytoprotective response in endothelial cells.

Erratum to "The peroxynitrite donor 3-morpholinosydnonimine activates Nrf2 and the UPR leading to a cytoprotective response in endothelial cells" [Cell. Signal. 24 (2012) 199-213]

Abstract

Similar works

Full text

Available Versions

Repository of the University of Namur

Repository of the University of Namur

Repository of the University of Namur

DI-fusion

DI-fusion

Repository of the University of Namur