Renal Ischemia Tolerance Mediated by eIF5A Hypusination Inhibition Is Regulated by a Specific Modulation of the Endoplasmic Reticulum Stress.

Autor: Melis N; Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Rubera I; Université Côte d'Azur, CNRS, LP2M, 06108 Nice, France.; Laboratories of Excellence Ion Channel Science and Therapeutics, 06103 Nice, France., Giraud S; INSERM U1313, IRMETIST, Université de Poitiers et CHU de Poitiers, 86000 Poitiers, France., Cougnon M; Université Côte d'Azur, CNRS, LP2M, 06108 Nice, France.; Laboratories of Excellence Ion Channel Science and Therapeutics, 06103 Nice, France., Duranton C; Université Côte d'Azur, CNRS, LP2M, 06108 Nice, France.; Laboratories of Excellence Ion Channel Science and Therapeutics, 06103 Nice, France., Poet M; Université Côte d'Azur, CNRS, LP2M, 06108 Nice, France.; Laboratories of Excellence Ion Channel Science and Therapeutics, 06103 Nice, France., Jarretou G; Université Côte d'Azur, CNRS, LP2M, 06108 Nice, France.; Laboratories of Excellence Ion Channel Science and Therapeutics, 06103 Nice, France., Thuillier R; INSERM U1313, IRMETIST, Université de Poitiers et CHU de Poitiers, 86000 Poitiers, France., Counillon L; Université Côte d'Azur, CNRS, LP2M, 06108 Nice, France.; Laboratories of Excellence Ion Channel Science and Therapeutics, 06103 Nice, France., Hauet T; INSERM U1313, IRMETIST, Université de Poitiers et CHU de Poitiers, 86000 Poitiers, France., Pellerin L; INSERM U1313, IRMETIST, Université de Poitiers et CHU de Poitiers, 86000 Poitiers, France., Tauc M; Université Côte d'Azur, CNRS, LP2M, 06108 Nice, France.; Laboratories of Excellence Ion Channel Science and Therapeutics, 06103 Nice, France., Pisani DF; Université Côte d'Azur, CNRS, LP2M, 06108 Nice, France.; Laboratories of Excellence Ion Channel Science and Therapeutics, 06103 Nice, France.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 Jan 25; Vol. 12 (3). Date of Electronic Publication: 2023 Jan 25.
DOI: 10.3390/cells12030409
Abstrakt: 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.
Databáze: MEDLINE
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