title: Effects of oxidative stress on intestinal type I insulin-like growth factor receptor expression.
abstract: BACKGROUND
  Oxidative stress activates multiple signaling transduction pathways, including the phosphatidylinositol 3-kinase (PI3-K), in an injured intestine as occurs in necrotizing enterocolitis (NEC). We have previously shown that hydrogen peroxide (H2O2)-induced PI3-K activation is significantly enhanced with exogenous insulin-like growth factor (IGF)-1 in intestinal epithelial cells. However, the effects of oxidative stress on IGF receptor type I (IGF-IR) activation and expression in the neonatal intestine during NEC are unknown.
  
  
  METHODS
  Intestinal sections from neonates undergoing bowel resections (control = 3, NEC = 20) were analyzed for IGF-IR expression. NEC was induced in newborn mouse pups using hypoxia and hyperosmolar feeds, and distal small bowel segments were analyzed for IGF-IR expression (control = 3, NEC = 7). H2O2 was used to induce oxidative stress in rat (RIE-1) and fetal human (FHs74 Int) intestinal epithelial cells. Phosphorylation of IGF-IR, Akt, a downstream effector of PI3-K, and IGF-IR levels were determined by Western blotting. Flow cytometry, immunofluorescence, immunohistochemistry, IGF-IR tyrosine phosphorylation array, cell death enzyme-linked immunosorbent assay, and Western blotting were used to determine the IGF-IR expression.
  
  
  RESULTS
  An increased IGF-IR expression was noted in intestinal sections from NEC as well as murine model of NEC. H2O2 treatment rapidly activated IGF-IR and increased the expression in RIE-1 and FHs74 Int cells. Inhibition of IGF-IR resulted in significant RIE-1 cell apoptosis during oxidative stress. IGF-IR tyrosine phosphorylation array showed the recruitment of several key SH2 domain-containing proteins and oncogenes to the IGF-IR tyrosine kinase domain in H2O2-treated RIE-1 cells.
  
  
  CONCLUSIONS
  IGF-IR-mediated activation of intracellular signaling may play a critical role during oxidative stress-induced apoptosis in NEC.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas 37232, USA.
authors.forename: N
authors.initials: N
authors.lastname: Baregamian
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.forename: D H
authors.initials: DH
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D020345:Enterocolitis, Necrotizing / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress; D010766:Phosphorylation; D011897:Random Allocation; D051381:Rats; D017451:Receptors, Somatomedin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017451:Receptors, Somatomedin