The Relevance of the UPS in Fatty Liver Graft Preservation: A New Approach for IGL-1 and HTK Solutions

Panisello‐Roselló, Arnau; Verde, Eva; Zaoualí, Mohamed Amine; Flores, Marta; Alva, Norma; Lopez, Alexandre; Folch-Puy, Emma; Carbonell, Teresa; Hotter, Georgina; Adam, René; Roselló‐Catafau, Joan

doi:10.3390/ijms18112287

Cited by 17 publications

(23 citation statements)

References 30 publications

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“…It has always appeared that autophagy within lysosomes is involved in the pathogenesis of hepatic IRI, although the specific alterations it causes and their subsequent functional significance are highly controversial[ 68 ]. The use of proteasome inhibitors has been demonstrated to enhance myocardial viability[ 69 , 70 ] and protect liver against IRI[ 4 , 71 - 73 ], which suggests this may be a promising strategy to reduce the damage inherent to transplantation protocols.…”

Section: The Ubiquitin-proteasome Systemmentioning

confidence: 99%

Ubiquitin-proteasome system and oxidative stress in liver transplantation

Alva

Panisello‐Roselló

Flores

et al. 2018

WJG

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A major issue in organ transplantation is the development of a protocol that can preserve organs under optimal conditions. Damage to organs is commonly a consequence of flow deprivation and oxygen starvation following the restoration of blood flow and reoxygenation. This is known as ischemia-reperfusion injury (IRI): a complex multifactorial process that causes cell damage. While the oxygen deprivation due to ischemia depletes cell energy, subsequent tissue oxygenation due to reperfusion induces many cascades, from reactive oxygen species production to apoptosis initiation. Autophagy has also been identified in the pathogenesis of IRI, although such alterations and their subsequent functional significance are controversial. Moreover, proteasome activation may be a relevant pathophysiological mechanism. Different strategies have been adopted to limit IRI damage, including the supplementation of commercial preservation media with pharmacological agents or additives. In this review, we focus on novel strategies related to the ubiquitin proteasome system and oxidative stress inhibition, which have been used to minimize damage in liver transplantation.

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Section: The Ubiquitin-proteasome Systemmentioning

confidence: 99%

Ubiquitin-proteasome system and oxidative stress in liver transplantation

Alva

Panisello‐Roselló

Flores

et al. 2018

WJG

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“…Data reported here are consistent with previously ones published by our group when IGL-1 and HTK were compared. Under the same conditions as this present study, AMP-activated protein kinase (AMPK) levels were higher in its active isoform (pAMPK) when IGL-1 solution was used [ 14 ]. Bibliography reports the existence of the AMPK/mTOR/autophagy axis [ 25 ] which has never been demonstrated before under our experimental conditions, and it takes special relevance as a possible protective target for liver graft conditioning during organ preservation, in order to limit organ injury and to maintain the graft quality before transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…The surgical procedures were carried out as described elsewhere [ 14 ]. After cannulation of the common bile duct, the portal vein was isolated and the splenic and gastroduodenal veins were ligated.…”

Section: Methodsmentioning

confidence: 99%

“…In accordance with this, Meine and cols have recently reported that the use of HTK in liver transplantation trials evidenced higher ischemia-reperfusion damage during the first postoperative days than IGL-1 solution [ 11 ]. In a previous work we demonstrated the relevance of AMP-activated protein kinase (AMPK) in fatty liver preservation when IGL-1 was used and compared to HTK [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK

Panisello‐Roselló

Verde

Lopez

et al. 2018

IJMS

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Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR) signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT), histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures.

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“…Proteasome inhibition is also important for fatty liver graft preservation by cold storage. Panisello-Roselló et al [ 26 ] evaluated the relevance of the ubiquitin system in cytoprotection during cold storage using Institut Georges Lopez (IGL)-1 and histidine-tryptophan-ketoglutarate (HTK) solutions. The IGL-1 solution provided a better cytoprotective effect on fatty liver grafts than did the HTK solution; this is likely to be through low ubiquitin–proteasome activity, increased endothelial nitric oxide synthase (e-NOS) expression, and AMP kinase (AMPK) signaling.…”

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confidence: 99%