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Issue title: Selected Papers from the 28th Congress on Clinical Hemorheology and Microcirculation of the German Society, Munich, Germany, 20–21 November 2009
Article type: Research Article
Authors: Waldow, Thomas | Witt, Wolfgang | Matschke, Klaus
Affiliations: Clinic for Cardiac Surgery, University Hospital Dresden, Technical University Dresden, Dresden, Germany
Note: [] Corresponding author: Dr. T. Waldow, Herzzentrum Dresden GmbH, Fetscherstr. 76, 01307 Dresden, Germany. Tel.: +49 351 450 1540; Fax: +49 351 450 1512; E-mail: [email protected]
Abstract: Recent studies on the mechanisms of ischemic preconditioning in myocardial tissue have presented convincing evidence that multiple protective pathways converge on inhibition of glycogen synthase kinase-3β (GSK-3β). To directly address the role of GSK-3β in ischemia and reperfusion (I/R) of the lung, a rat model of left lung in situ ischemia was used. The specific non-competitive inhibitor of GSK-3β, TDZD-8, was injected (3 mg/kg, vehicle in controls) 5 min before the left lung hilum was occluded for 60 min. Animals in the ischemia group underwent the same treatment, but without administration of TDZD-8. Lung functional and biochemical parameters were determined at time points 15 min and 60 min reperfusion. Treatment with TDZD-8 improved gas exchange (arterial pO2), but I/R-induced inflammation (plasma interleukin-6, leukocyte invasion) was not affected. The I/R cycle induced a rapid (15 min reperfusion) increase of protein tyrosine phosphorylation, including the activating phosphorylation of focal adhesion kinase at Tyr397, Tyr407, Tyr577, and Tyr861, and the non-receptor kinase Src at Tyr416. The phosphorylation was blocked by the GSK inhibitor. This effect may be related to the reduced plasma level of the strong effector of focal adhesion kinase, transforming growth factor-β1, in the TDZD group. The underlying mechanisms are elusive, but they deserve further investigation, especially in relation to the early increase of lung permeability in this rat model of I/R injury. In conclusion, the results suggest that inhibition of GSK-3β improves rat lung function during an I/R cycle, but only during the early reperfusion phase.
Keywords: Glycogen synthase kinase, ischemia/reperfusion, focal adhesion kinase, TGF-beta1, Src
DOI: 10.3233/CH-2010-1343
Journal: Clinical Hemorheology and Microcirculation, vol. 46, no. 2-3, pp. 169-181, 2010
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