Purpose: 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 2O 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 2O 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.
|Number of pages||7|
|Journal||Pediatric Surgery International|
|State||Published - Aug 2011|
Bibliographical noteFunding Information:
The authors thank Karen Martin for manuscript preparation. This work was supported by grants R01 DK61470, R01 DK48498, P01 DK35608 and T32 DK07639 from the National Institutes of Health and a grant 8580 from Shriners Hospital for Children.
- Growth factors
- Intestinal epithelial cells
- Mitochondrial apoptotic signaling
- Necrotizing enterocolitis
- Oxidative stress
- Reactive oxygen species
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health