TY - JOUR
T1 - Intestinal mitochondrial apoptotic signaling is activated during oxidative stress
AU - Baregamian, Naira
AU - Song, Jun
AU - Papaconstantinou, John
AU - Hawkins, Hal K.
AU - Evers, B. Mark
AU - Chung, Dai H.
N1 - Funding 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.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Growth factors
KW - Intestinal epithelial cells
KW - Mitochondrial apoptotic signaling
KW - Necrotizing enterocolitis
KW - Oxidative stress
KW - Reactive oxygen species
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U2 - 10.1007/s00383-011-2880-x
DO - 10.1007/s00383-011-2880-x
M3 - Article
C2 - 21400030
AN - SCOPUS:79961173427
SN - 0179-0358
VL - 27
SP - 871
EP - 877
JO - Pediatric Surgery International
JF - Pediatric Surgery International
IS - 8
ER -