1. Suppression of the p66shc adapter protein by protocatechuic acid prevents the development of lung injury induced by intestinal ischemia reperfusion in mice.
- Author
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Wang GZ, Yao JH, Jing HR, Zhang F, Lin MS, Shi L, Wu H, Gao DY, Liu KX, and Tian XF
- Subjects
- Animals, Disease Models, Animal, Lung Injury etiology, Male, Mice, Mice, Inbred ICR, RNA, Messenger metabolism, Reperfusion Injury etiology, Reperfusion Injury pathology, Shc Signaling Adaptor Proteins genetics, Src Homology 2 Domain-Containing, Transforming Protein 1, Superoxide Dismutase metabolism, bcl-X Protein metabolism, Anticarcinogenic Agents therapeutic use, Hydroxybenzoates therapeutic use, Lung Injury metabolism, Lung Injury prevention & control, Reperfusion Injury metabolism, Shc Signaling Adaptor Proteins metabolism
- Abstract
Background: Intestinal ischemia/reperfusion (I/R) causes severe histological injury, reactive oxygen species activation, and cell apoptosis in the lung. In this study, we investigated, using a murine intestinal I/R model, the effect of a polyphenolic compound, protocatechuic acid (PCA), in modulation of ShcA and in protection of the lung from I/R-induced injury., Methods: Fifty ICR mice were randomly divided into five groups, including a control group, intestinal I/R group, control + PCA group, I/R + PCA low-dose group, and I/R + PCA high-dose group. The I/R and I/R + PCA groups were subjected to mesenteric arterial ischemia for 45 minutes and reperfusion for 90 minutes. The control and control + PCA groups underwent a surgical procedure that included isolation of the superior mesenteric artery without occlusion. In all PCA-pretreated groups, the mice received intraperitoneal PCA administration for three consecutive days. Serum specimens were collected for measuring tumor necrosis factor-α and interleukin 6, while lung tissues were harvested for histopathologic assessment including glutathione (GSH) and GSH peroxidase assay. Lung expression of p66shc, phosphorylated p66shc, manganese superoxide dismutase, caspace-3, and Bcl-xL were determined by Western blotting for protein level and semiquantitative reverse transcription-polymerase chain reaction analysis for mRNA level., Results: PCA pretreatment markedly reduced I/R-induced lung injury as indicated by histological alterations; the decreases in tumor necrosis factor-α, interleukin 6, and caspase-3 expression levels; and the increases in GSH, GSH peroxidase, manganese superoxide dismutase, and Bcl-xL levels in the lung. Moreover, PCA treatment down-regulated p66shc expression and phosphorylation., Conclusion: PCA has a significant protective effect in lung injury induced by intestinal I/R. The protective effect of PCA may be attributed to the suppression of p66shc and the modulation of downstream antioxidative/antiapoptotic factors.
- Published
- 2012
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