Organ dysfunction secondary to ischemia-reperfusion (I/R) injury still represents a major problem in liver transplantation. Apoptosis has been observed in hepatocytes and sinusoidal endothelial cell, following I/R injury and it has been postulated as a contributing factor in ischemia-reperfusion graft dysfunction, involving a complex series of events, as changes of protein tyrosine-kinase phosphorylation. We evaluated hepatic purine metabolites, protein tyrosine phosphatases (PTPs), nitrate plus nitrite levels (NOx), caspase-3 (C-3) activity and DNA fragmentation in the time course of twelve pig orthotopic liver transplantation. Biopsies were taken before explantation (t0), after cold ischemic storage (t1) and 30 min from reperfusion (t2). During the ischemic period we observed a reduction of high energy phosphates and an increase of purine bases; PTP activity was largely increased. At t2 high energy phosphates showed a tendency to increase with respect to t1, with a partial restoration of phosphorylation potential, measured as ATP/ADT ratio. PTP activity was significantly reduced, with a concomitant increase of NOx production and C-3 activity; in a considerable number of cases we observed a sustained DNA fragmentation. We speculate that NOx production could be related to nitrosative stress, which in turn leads to dynamic alteration in PTP balance and cell signalling, regulating the activity of a number of proteins implicated in apoptotic cell death. These findings could be of interest in new potential strategy to prevent and treat I/R injury.

NITRIC OXIDE GENERATION IS ASSOCIATED WITH AN UNBALANCE OF PROTEIN TYROSINE PHOSPHATASES DURING LIVER TRANSPLANTATION / Carlucci, F; Marinello, E; Rosi, F; Floccari, F; Gerunda, Giorgio Enrico; Neri, D; Tabucchi, A.. - In: BIOMÉDECINE & PHARMACOTHÉRAPIE. - ISSN 0753-3322. - STAMPA. - 61:4(2007), pp. 216-221. [10.1016/j.biopha.2007.03.005]

NITRIC OXIDE GENERATION IS ASSOCIATED WITH AN UNBALANCE OF PROTEIN TYROSINE PHOSPHATASES DURING LIVER TRANSPLANTATION

GERUNDA, Giorgio Enrico;
2007

Abstract

Organ dysfunction secondary to ischemia-reperfusion (I/R) injury still represents a major problem in liver transplantation. Apoptosis has been observed in hepatocytes and sinusoidal endothelial cell, following I/R injury and it has been postulated as a contributing factor in ischemia-reperfusion graft dysfunction, involving a complex series of events, as changes of protein tyrosine-kinase phosphorylation. We evaluated hepatic purine metabolites, protein tyrosine phosphatases (PTPs), nitrate plus nitrite levels (NOx), caspase-3 (C-3) activity and DNA fragmentation in the time course of twelve pig orthotopic liver transplantation. Biopsies were taken before explantation (t0), after cold ischemic storage (t1) and 30 min from reperfusion (t2). During the ischemic period we observed a reduction of high energy phosphates and an increase of purine bases; PTP activity was largely increased. At t2 high energy phosphates showed a tendency to increase with respect to t1, with a partial restoration of phosphorylation potential, measured as ATP/ADT ratio. PTP activity was significantly reduced, with a concomitant increase of NOx production and C-3 activity; in a considerable number of cases we observed a sustained DNA fragmentation. We speculate that NOx production could be related to nitrosative stress, which in turn leads to dynamic alteration in PTP balance and cell signalling, regulating the activity of a number of proteins implicated in apoptotic cell death. These findings could be of interest in new potential strategy to prevent and treat I/R injury.
2007
61
4
216
221
NITRIC OXIDE GENERATION IS ASSOCIATED WITH AN UNBALANCE OF PROTEIN TYROSINE PHOSPHATASES DURING LIVER TRANSPLANTATION / Carlucci, F; Marinello, E; Rosi, F; Floccari, F; Gerunda, Giorgio Enrico; Neri, D; Tabucchi, A.. - In: BIOMÉDECINE & PHARMACOTHÉRAPIE. - ISSN 0753-3322. - STAMPA. - 61:4(2007), pp. 216-221. [10.1016/j.biopha.2007.03.005]
Carlucci, F; Marinello, E; Rosi, F; Floccari, F; Gerunda, Giorgio Enrico; Neri, D; Tabucchi, A.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/610487
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 4
social impact