Organ preservationIschemia–reperfusion decreases protein tyrosine phosphorylation and p38 mitogen-activated protein kinase phosphorylation in rat lung transplants☆
Section snippets
Animals
Inbred male Lewis (LEW; RT-1l; 250 to 350 g) rats and inbred male Brown Norway (BN; RT-1n; 250 to 350 g) rats were obtained from Charles River, Inc. (Montreal, Quebec, Canada). All animals received humane care in compliance with The Principles of Laboratory Animal Care, formulated by the Institute of Laboratory Animal Resources (Toronto, ON, Canada); the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 86-23, revised 1985); and the Guide to the Care and Use of Experimental
Airway pressures, arterial blood gases and wet/dry lung ratio
To determine the impact of allogeneic vs isogeneic responses on lung function during reperfusion, arterial blood gases and wet/dry lung weight ratio were used to compare the lung oxygenation and degree of pulmonary edema after reperfusion between isogeneic and allogeneic transplants. Before harvest, the Pao2 of the donor lungs was >580 mmHg and, after 2 hours of reperfusion, the Pao2 of blood returning from of the donor lung alone was >430 mmHg. The oxygenation function of lung grafts was
Discussion
In this study, the status of protein tyrosine phosphorylation was examined in a rat single-lung transplant model that simulates the clinical lung transplant setting of cold ischemic preservation for 6 hours, followed by lung implantation (warm ischemia) and reperfusion. Both iso- and allografts showed satisfactory pulmonary function after reperfusion. A dramatic decrease in protein tyrosine phosphorylation was observed after a 2-hour period of reperfusion, similar to Src PTK activity and Src
Acknowledgements
The authors thank John Mates, Xiao-Hui Bai, Monika Lodyga and Julia Hamilton for technical assistance. M. Liu is a recipient of the Premier’s Research Excellence Award from the Government of Ontario, Canada.
References (32)
- et al.
The registry of the International Society for Heart and Lung Transplantationseventeenth official report—2000
J Heart Lung Transplant
(2000) - et al.
Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation
Ann Thorac Surg
(2000) - et al.
Inhibition of angiotensin-converting enzyme by captoprila novel approach to reduce ischemia–reperfusion injury after lung transplantation
J Thorac Cardiovasc Surg
(2000) - et al.
Raffinose improves the function of rat pulmonary grafts stored for twenty-four hours in low-potassium dextran solution
J Thorac Cardiovasc Surg
(2000) - et al.
Raffinose improves 24-hour lung preservation in low potassium dextran glucose solutiona histologic and ultrastructural analysis
Ann Thorac Surg
(2001) - et al.
Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney
J Biol Chem
(1997) - et al.
Purification and characterization of a protein tyrosine phosphatase containing SH2 domains
J Biol Chem
(1993) - et al.
Mechanical strain induces pp60src activation and translocation to cytoskeleton in fetal rat lung cells
J Biol Chem
(1996) - et al.
Serine/threonine protein kinases and apoptosis
Exp Cell Res
(2000) - et al.
Requirement of activation of JNK and p38 for environmental stress-induced erythroid differentiation and apoptosis and of inhibition of ERK for apoptosis
Blood
(1999)
Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta
J Biol Chem
Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family
J Biol Chem
Lung transplantationstate of art
Am J Respir Crit Care Med
Cell death in human lung transplantationapoptosis induction in human lungs during ischemia and after transplantation
Ann Surg
Dynamic changes in apoptotic and necrotic cell death correlate with severity of ischemia–reperfusion injury in lung transplantation
Am J Respir Crit Care Med
Inhibitors of tyrosine phosphorylation induce apoptosis in human leukemic cell lines
Leukemia
Cited by (20)
Protective effects of anti-HMGB1 monoclonal antibody on lung ischemia reperfusion injury in mice
2021, Biochemical and Biophysical Research CommunicationsCitation Excerpt :These results were strongly associated with the results of lung oxygenation, lung injury score, and neutrophil infiltration, indicating that anti-HMGB1 mAb treatment can reduce lung IR injury by inhibiting the expression of proinflammatory mediators. MAPK signaling is widely accepted as a downstream target of RAGE and TLR, and some experiments have shown that inhibition of p38 MAPK can improve lung function, reduce proinflammatory cytokine levels, and decrease neutrophil infiltration in lung IR and transplantation models [18,19]. In our study, the phosphorylation of p38 increased in the IR injury group and the expression of phosphorylated p38 could be reduced by anti-HMGB1 mAb.
Sevoflurane Attenuates Ischemia-Reperfusion Injury in a Rat Lung Transplantation Model
2017, Annals of Thoracic SurgeryCitation Excerpt :IRI is a complex process involving the accumulation of neutrophils, the generation and release of inflammatory cytokines, and the development of cell death. This is a significant cause of early morbidity and mortality after LTx and is associated with long-term graft dysfunction [22, 23]. Multiple studies have shown that volatile anesthetics can be used for both preconditioning and postconditioning to reduce IRI in various organs, such as the heart, kidney, liver, central nervous system, and lungs [24–28].
Effect of NADPH oxidase inhibitor-apocynin on the expression of Src homology-2 domain-containing phosphatase-1 (SHP-1) exposed renal ischemia/reperfusion injury in rats
2015, Toxicology ReportsCitation Excerpt :However, Ischemia/reperfusion (I/R) injury produced a lot of oxygen free radicals (OFR) and these elevated level of OFR can inhibit the phosphatase activity of SHP-1, and the function of SHP-1 was restrained to promote the release of OFR [7,8]. During the early IR period of lung transplantation, the activity of PTP was reduced [14]. Present study indicated that RI/RI can produce lots of OFR [6] and inflammatory factors [15] which can inhibit the activity of SHP-1, and loss of activity of SHP-1 can further exacerbate the damage of RI/RI [9,16–18].
Hypoxia followed by re-oxygenation induces oxidation of tyrosine phosphatases
2011, Cellular SignallingCitation Excerpt :There are conflicting reports about PTP activity in cellular- or tissue-based models of reoxygenation and reperfusion. While no change in PTP-activity was shown in brain ischemia/reperfusion [51], liver transplantation was associated with significantly decreased PTP-activity [52,53], which is in line with our data in fibroblasts, cardiomyocytes, and in heart tissues. There has been, however, no data regarding the underlying mechanism of reduced PTP activity under conditions of hypoxia/reoxygenation and ischemia/reperfusion.
Preconditioning by inhaled nitric oxide prevents hyperoxic and ischemia/reperfusion injury in rat lungs
2008, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :The increase of MAPK activation has been observed in oxygen-ventilated mice already after 1 h, but only in combination with high tidal volume ventilation, whereas controls showed no response or a slight decrease in ERK phosphorylation compared to room air [55]. The reduction of p38 phosphorylation to about 10% of basis has been observed in the setting of rat lung transplantation after 2 h of 100% oxygen ventilation in the reperfusion phase [56]. In the report of Morse et al. [51] on hyperoxia in an mouse model, the short-term data were not quantified, but visual inspection of the blots may indicate that JNK was inactivated after one day of exposure before activation set in after two days.
Activation of mitogen-activated protein kinases during human lung transplantation
2005, Journal of Heart and Lung Transplantation
- ☆
Supported by the Ontario Thoracic Society, the Canadian Cystic Fibrosis Foundation and the Canada Institutes of Health Research (MT-13270, MOP-42465, MOP-77559).