Ischemia-reperfusion decreases protein tyrosine phosphorylation and p38 mitogen-activated protein kinase phosphorylation in rat lung transplants.
BACKGROUND
Dramatic alterations of protein tyrosine phosphorylation have been found during the ischemia-reperfusion (IR) period of human lung transplantation. IR also induces activation of p38 mitogen-activated protein kinase (p38) in the heart and kidney. The objective of the present study was to determine whether these changes exist in a rat single-lung transplant model for further mechanistic investigations.


METHODS
Isogeneic lung transplantation was performed from Lewis (LEW) to LEW rats, whereas allogeneic transplantation was from LEW to Brown Norway (BN) rats. Blood gases and peak airway pressure were monitored. Lung tissues were collected after 6 hours of cold ischemic preservation, after 30 minutes of warm ischemia for lung implantation, and after 2 hours of reperfusion. Protein tyrosine kinase (PTK) and phosphatase (PTP) activities were measured. Protein tyrosine phosphorylation, Src PTK and p38 expression and p38 phosphorylation were examined by western blotting.


RESULTS
In both iso- and allografts, the lung function of transplants was very well preserved. Protein tyrosine phosphorylation, PTK and PTP activities were decreased significantly after 2 hours of reperfusion. Src protein level and phosphorylation of p38 were reduced after 2 hours of reperfusion.


CONCLUSIONS
During the early IR period of lung transplantation, decreased protein tyrosine phosphorylation may be involved in apoptosis and other biologic changes. The lack of p38 activation suggests that activity of mitogen-activated protein kinase pathways in the lung transplantation setting may be different from other IR processes.
Sakiyama
Shoji
S
University Health Network Toronto General Hospital, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
dePerrot
Marc
M
Han
Bing
B
Waddell
Thomas K
TK
Keshavjee
Shaf
S
Liu
M
M
D000818:Animals; D016040:Lung Transplantation; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009926:Organ Preservation; D010766:Phosphorylation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases