title: Intestinal mitochondrial apoptotic signaling is activated during oxidative stress.
abstract: OBJECTIVE
  Reactive oxygen species (ROS) are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC). Mitochondria as a major source of intracellular ROS and apoptotic signaling during oxidative stress in NEC have not been investigated. We sought to determine: (1) the effects of oxidative stress on intestinal mitochondrial apoptotic signaling, and (2) the role of growth factors in this process.
  
  
  METHODS
  We used Swiss-Webster mice pups, and rat intestinal epithelial (RIE)-1, mitochondrial DNA-depleted RIE-1 cell line (RIE-1-ρ°) and human fetal intestinal epithelial cells (FHs74 Int) for our studies.
  
  
  RESULTS
  H(2)O(2) induced apoptosis and ROS production. ROS-mediated activation of apoptotic signaling was significantly attenuated with mitochondrial silencing in RIE-1-ρ° cells. Growth factors, especially IGF-1, attenuated this response to H(2)O(2) in intestinal epithelial cells.
  
  
  CONCLUSIONS
  Our findings suggest that mitochondria are a major source of intestinal apoptotic signaling during oxidative stress, and modulating mitochondrial apoptotic responses may help ameliorate the effects of NEC.
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Naira
authors.initials: N
authors.lastname: Baregamian
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.forename: John
authors.initials: J
authors.lastname: Papaconstantinou
authors.forename: Hal K
authors.initials: HK
authors.lastname: Hawkins
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
authors.forename: Dai H
authors.initials: DH
authors.lastname: Chung
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D004247:DNA