Intestinal mitochondrial apoptotic signaling is activated during oxidative stress.

Abstract:

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(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.

journal_name

Pediatr Surg Int

authors

Baregamian N,Song J,Papaconstantinou J,Hawkins HK,Evers BM,Chung DH

doi

10.1007/s00383-011-2880-x

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

871-7

issue

8

eissn

0179-0358

issn

1437-9813

journal_volume

27

pub_type

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