Furthermore, the expression of the heat shock proteins HSP 70 and HO 1, which are induced immedi ately after ischaemia as organ protective mechanisms, was analysed. As a mediator of cellular inflammatory response, selleck compound phosphorylation of the transcription factor STAT3 at Inhibitors,Modulators,Libraries Y705, which among others is induced by IL 6, was assessed. We chose to analyse tissue samples from the heart, the lung, the liver and the kidney to demonstrate the sys temic effect of I R associated with the presented model. As a result of I R, organ specific phosphorylation and expression patterns could be detected, which were dis tinct for each of the investigated organs and will be dis cussed in the following paragraphs individually in detail. As a control for uniform loading and protein levels, pan cadherin was used because it gave better results than B actin and Tubulin.

A brief summary is Inhibitors,Modulators,Libraries pre sented in Table 3. Representative blots for ERK1 2, HSP 70 and STAT3 are displayed in Figure 4A B. The complete western blot results are shown in Additional file 3, Figure S2 and in Additional file 4, Figure S3 of the supplementary data. Heart I R induced a significant increase in the phosphorylation of cardiac ERK1 2 as compared to healthy animals. Similar results have been reported for rat models of ischae mic preconditioning and were attributed to the transloca tion of the signal mediator protein kinase C from the cytosol to mitochondria. Additionally, the involvement of cytokines in the present study is further indicated by in creased STAT3 phosphorylation in 4 of 5 I R animals in contrast to the healthy animals, where no phosphorylation was observed.

However, when JNK was analysed, as a con sequence of I R no change could be Inhibitors,Modulators,Libraries detected in both, the total protein expression and the phosphorylation status. Furthermore, in three out of five I R animals we observed a decrease of p38 MAPK phosphorylation, which may be due to the long reperfusion time. Similar effects have been previously observed in other rat models of isolated cardiac I R. Equally, three out of five I R animals showed a considerable increase of HSP 70 protein expression, matching the previously reported observa tions that HSP 70 expression is increased in myocar dial infarction and I R, potentially as a protective response. HO 1 protein expression did not differ be tween the two groups.

Lung As stated above, an increase of STAT3 protein phos phorylation was recognised in all analysed organs, in cluding the lungs. Moreover, I R induced a decrease of phosphorylated ERK1 2 and total ERK1 2 expression in comparison to Inhibitors,Modulators,Libraries healthy animals. Similarly, a decrease of both, phospho JNK and total JNK signals was detected. A decrease of phosphorylation was Inhibitors,Modulators,Libraries also www.selleckchem.com/products/3-deazaneplanocin-a-dznep.html visible on p38 MAPK. Based on existing reports I R is expected to acti vate MAP kinases.