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Figure 2. SPR activation with geldanamycin or PDTC significantly attenuates I/R-mediated lung injury in rats. A and B) SPR activation with geldanamycin or PDTC leads to increased expression of Hsp72 protein in the lung. Rats were left untreated or pretreated with geldanamycin (1 mg/kg i.p., 48 and 24 h before sacrifice) or PDTC (200 mg/kg i.p., 4 h before sacrifice). Animals were sacrificed, the lungs removed, and then examined for their expression of Hsp72 by Western blot analysis. One representative blot is shown. For all experiments, densitometry analysis results are the mean ± SEM of 4 experiments; *P < 0.05 from control experiments. C and D) SPR activation with geldanamycin or PDTC significantly attenuates I/R-mediated lung injury in rats. Extravascular plasma equivalents (µl/lung) are shown for control and ischemic lungs of rats that have been pretreated with geldanamycin or PDTC or their vehicle; (30 min ischemia and 180 min reperfusion); results are shown as means ± SEM; *P < 0.05 from control lung; **P < 0.05 from ischemic lung that did not undergo prior SPR activation. E) Effect of I/R injury and stress preconditioning with geldanamycin on lung tissue VEGF receptor type II (KDR/flk-1) phosphorylation in rats. KDR/flk-1 phosphorylation was measured in rat lungs that underwent I/R lung injury or sham surgery; in some experiments, rats were stress preconditioned with geldanamycin (1 mg/kg i.p., 48 and 24 h before sacrifice); lung tissues were harvested and subjected to immunoprecipitation with an Ab against vascular endothelial growth factor receptor type II protein and immunoblotted with an Ab to phosphotyrosine. The same blots were then reprobed with an Ab to vascular endothelial growth factor receptor type II protein. One representative blot is shown. For all experiments, densitometry analysis results are the mean ± SEM of 4 experiments; *P < 0.05 from control experiments.
