title: Suppression of the p66shc adapter protein by protocatechuic acid prevents the development of lung injury induced by intestinal ischemia reperfusion in mice.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Wang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Yao
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Jing
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Mu-Sen
authors.initials: MS
authors.lastname: Lin
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Hang
authors.initials: H
authors.lastname: Wu
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Gao
authors.forename: Ke-Xin
authors.initials: KX
authors.lastname: Liu
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tian
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D062385:Hydroxybenzoates / Q000627:therapeutic use*; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013482:Superoxide Dismutase / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; C494811:BCL2L1 protein, human; D062385:Hydroxybenzoates; D012333:RNA, Messenger; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D051020:bcl-X Protein; C009091:protocatechuic acid; D013482:Superoxide Dismutase