Decoding cold ischaemia time impact on kidney graft: the kinetics of the unfolded protein response pathways

Pape, Sylvain Le; Pasini-Chabot, Ophélie; Couturier, Pierre; Delpech, P.; Volmer, Romain; Quellard, Nathalie; Ploeg, Rutger J.; Hauet, Thierry; Thuillier, Raphaël

doi:10.1080/21691401.2018.1518908

Cited by 10 publications

(7 citation statements)

References 51 publications

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“…Interestingly, UPR stress pathways activation does not seem simultaneous in order to generate an adaptative response depending on intensity and duration of the ER stress. In this manner, it has been demonstrated that the endothelium displayed a time-dependent activation of UPR pathways in response to ER stress when endothelial cells are exposed to cold anoxia and normothermic reoxygenation [24]. In the present study, it could be shown that the ER stress response was regulated in close association with cold ischemia time.…”

Section: Introductionsupporting

confidence: 62%

“…GC7 treatment has been shown to induce a metabolic shift toward anaerobic glycolysis and limit oxidative stress generation, two effects protecting cells from O 2 deprivation [30,31]. Nevertheless, several studies demonstrated the key role of ER stress in the alteration of cell function and survival during ischemia/reperfusion [24]. To determine if GC7 was able to protect cells from cell death induced by UPR activation, we treated cells with 10 µg/mL of tunicamycin which is a well-known inductor of ER stress.…”

Section: Gc7 Preconditioning Prevents Anoxia-and Tunicamycin-induced ...mentioning

confidence: 99%

“…In contrast, the ATF6 pathway was activated later and associated with cell death, while the IRE-1α -XBP1 pathway was activated only at the reoxygenation stage. Both ATF6 and IRE-1α (independently of XBP1) induced CHOP expression during cold ischemia and reoxygenation, and their inhibitions allowed to increase cell survival [24].…”

Section: Introductionmentioning

confidence: 99%

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

Melis

Rubera

Giraud

et al. 2023

Cells

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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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Section: Introductionsupporting

confidence: 62%

Section: Gc7 Preconditioning Prevents Anoxia-and Tunicamycin-induced ...mentioning

confidence: 99%

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

Melis

Rubera

Giraud

et al. 2023

Cells

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“…There exists a certain time-dependent molecular detriment mechanism since the effect of different CIT durations can be significantly different. Le Pape et al ( 27 ) demonstrated that the unfolded protein response plays a critical role in elaborating the relationship between CIT and transplant outcomes. During the first 1–8 h, the eIF2a-ATF4 pathway is inhibited, while ATF6 is activated at 12–24 h and is associated with cell death.…”

Section: Discussionmentioning

confidence: 99%

Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients

Luo

Dong

et al. 2021

Front. Med.

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Objectives: We aimed to analyze the effect of cold ischemia time (CIT) on post-transplant graft function through mixed-effect model analysis to reduce the bias caused by paired mate kidneys.Methods: We reviewed all kidney transplantation records from 2015 to 2019 at our center. After applying the exclusion criteria, 561 cases were included for analysis. All donor characteristics, preservation and matching information, and recipient characteristics were collected. Transplant outcomes included delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). Generalized linear mixed models were applied for analysis. We also explored potential effect modifiers, namely, donor death category, expanded criteria donors, and donor death causes.Results: Among the 561 cases, 79 DGF recipients developed DGF, and 15 recipients who died after surgery were excluded from the eGFR estimation. The median stable eGFR of the 546 recipients was 60.39 (47.63, 76.97) ml/min/1.73 m2. After adjusting for confounding covariates, CIT had a negative impact on DGF incidence [odds ratio = 1.149 (1.006, 1.313), P = 0.041]. In the evaluation of the impact on eGFR, the regression showed that CIT had no significant correlation with eGFR [β = −0.287 (−0.625, 0.051), P = 0.096]. When exploring potential effect modifiers, only the death category showed a significant interaction with CIT in the effect on eGFR (Pinteraction = 0.027). In the donation after brain death (DBD) group, CIT had no significant effect on eGFR [β = 0.135 (−0.433, 0.702), P = 0.642]. In the donation after circulatory death/donation after brain death followed by circulatory death (DCD/DBCD) group, CIT had a significantly negative effect on eGFR [β= −0.700 (−1.196, −0.204), P = 0.006]. Compared to a CIT of 0–6 h, a CIT of 6–8 or 8–12 h did not decrease the post-transplant eGFR. CIT over 12 h (12–16 h or over 16 h) significantly decreased eGFR. With the increase in CIT, the regenerated eGFR worsened (Ptrend = 0.011).Conclusion: Considering the effect of paired mate kidneys, the risk of DGF increased with prolonged CIT. The donor death category was an effect modifier between CIT and eGFR. Prolonged CIT did not reduce the eGFR level in recipients from DBDs but significantly decreased the eGFR in recipients from DCDs/DBCDs. This result indicates the potential biological interaction between CIT and donor death category.

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“…This process can cause PNF or DGF and episodes of acute rejection and transplant fibrosis. Notably, 12 h is the preservation time after which reperfusion induces cell death, with an intensity proportional to the preservation time [ 29 , 30 ].…”

Section: Clinical Applications Of Proteomics In Kidney Transplantationmentioning

confidence: 99%

Biomarker-Development Proteomics in Kidney Transplantation: An Updated Review

Sirolli

Piscitani

Bonomini

2023

IJMS

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Kidney transplantation (KT) is the optimal therapeutic strategy for patients with end-stage renal disease. The key to post-transplantation management is careful surveillance of allograft function. Kidney injury may occur from several different causes that require different patient management approaches. However, routine clinical monitoring has several limitations and detects alterations only at a later stage of graft damage. Accurate new noninvasive biomarker molecules are clearly needed for continuous monitoring after KT in the hope that early diagnosis of allograft dysfunction will lead to an improvement in the clinical outcome. The advent of “omics sciences”, and in particular of proteomic technologies, has revolutionized medical research. Proteomic technologies allow us to achieve the identification, quantification, and functional characterization of proteins/peptides in biological samples such as urine or blood through supervised or targeted analysis. Many studies have investigated proteomic techniques as potential molecular markers discriminating among or predicting allograft outcomes. Proteomic studies in KT have explored the whole transplant process: donor, organ procurement, preservation, and posttransplant surgery. The current article reviews the most recent findings on proteomic studies in the setting of renal transplantation in order to better understand the effective potential of this new diagnostic approach.

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Decoding cold ischaemia time impact on kidney graft: the kinetics of the unfolded protein response pathways

Cited by 10 publications

References 51 publications

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

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

Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients

Biomarker-Development Proteomics in Kidney Transplantation: An Updated Review

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