Format du dépôt |
Fichier |
Type de dépôt |
Article dans une revue |
Titre |
en
Renal Ischemia Tolerance Mediated by eIF5A Hypusination Inhibition Is Regulated by a Specific Modulation of the Endoplasmic Reticulum Stress
|
Résumé |
en
Through kidney transplantation, ischemia/reperfusion is known to induce tissular injury due to cell energy shortage, oxidative stress, and endoplasmic reticulum (ER) stress. ER stress stems from an accumulation of unfolded or misfolded proteins in the lumen of ER, resulting in the unfolded protein response (UPR). Adaptive UPR pathways can either restore protein homeostasis or can turn into a stress pathway leading to apoptosis. We have demonstrated that N1-guanyl-1,7-diamineoheptane (GC7), a specific inhibitor of eukaryotic Initiation Factor 5A (eIF5A) hypusination, confers an ischemic protection of kidney cells by tuning their metabolism and decreasing oxidative stress, but its role on ER stress was unknown. To explore this, we used kidney cells pretreated with GC7 and submitted to either warm or cold anoxia. GC7 pretreatment promoted cell survival in an anoxic environment concomitantly to an increase in xbp1 splicing and BiP level while eiF2α phosphorylation and ATF6 nuclear level decreased. These demonstrated a specific modulation of UPR pathways. Interestingly, the pharmacological inhibition of xbp1 splicing reversed the protective effect of GC7 against anoxia. Our results demonstrated that eIF5A hypusination inhibition modulates distinctive UPR pathways, a crucial mechanism for the protection against anoxia/reoxygenation.
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Auteur(s)
|
Nicolas Melis
1
, Isabelle Rubera
2, 3
, Sebastien Giraud
4
, Marc Cougnon
2, 3
, Christophe Duranton
2, 3
, Mallorie Poet
2, 3
, Gisèle Jarretou
2, 3
, Raphaël Thuillier
4
, Laurent Counillon
2, 3
, Thierry Hauet
4
, Luc Pellerin
4
, Michel Tauc
2, 3
, Didier Pisani
2, 3
1
NCI-NIH -
National Cancer Institute [Bethesda]
( 305678 )
- BG 9609 MSC 9760, 9609 Medical Center Drive, Bethesda, MD 20892-9760
- États-Unis
-
National Institutes of Health [Bethesda, MD, USA] ( 1182789 )
2
LP2M -
Laboratoire de PhysioMédecine Moléculaire
( 201743 )
- Parc Valrose 06108 Nice Cedex 2
- France
-
Université Nice Sophia Antipolis (1965 - 2019) ( 117617 )
;
-
Centre National de la Recherche Scientifique UMR7370 / FRE3472 ( 441569 )
;
-
Université Côte d'Azur ( 1039632 )
3
LabEx ICST -
Laboratory of Excellence in Ion Channel Science and Therapeutics [Valbonne]
( 1003226 )
- France
-
Institut de pharmacologie moléculaire et cellulaire ( 199361 )
;
-
Université Nice Sophia Antipolis (1965 - 2019) ( 117617 )
;
-
Centre National de la Recherche Scientifique UMR7275 ( 441569 )
;
-
Université Côte d'Azur ( 1039632 )
4
IRMETIST [Poitiers] -
Ischémie reperfusion, métabolisme et inflammation stérile en transplantation [U 1313]
( 1089072 )
- CHU de Poitiers – 2 rue de la Milétrie – CS 90577 – 86021 Poitiers Cedex – France
- France
-
Université de Poitiers = University of Poitiers UMR-S 1313 ( 54493 )
;
-
Institut National de la Santé et de la Recherche Médicale U1313 ( 303623 )
|
Langue du document |
Anglais
|
Licence |
Paternité
|
Nom de la revue |
|
Date de publication |
2023-02
|
Volume |
12
|
Numéro |
3
|
Page/Identifiant |
409
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Projet(s) ANR |
|
Domaine(s) |
-
Sciences du Vivant [q-bio]
|
Mots-clés |
en
GC7, hypusine, preconditioning, XBP1, BiP, anoxia, kidney
|
DOI |
10.3390/cells12030409 |
Pubmed Id |
36766751 |