IGF-1 Protects Intestinal Epithelial Cells From Oxidative Stress-Induced Apoptosis

Naira Baregamian, Jun Song, Marc G. Jeschke, B. Mark Evers, Dai H. Chung

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Background: Reactive oxygen species (ROS) are involved in the pathogenesis of necrotizing enterocolitis (NEC) in premature infants. We have recently found that activation of multiple cellular signaling transduction pathways occurs during ROS-induced intestinal cell apoptosis; the phosphatidylinositol 3-kinase (PI3-K) pathway plays an anti-apoptotic role during this process. Insulin-like growth factor (IGF)-1 activates PI3-K pathway to promote cell survival; however, the effects of IGF-1 treatment during gut injury are not clearly defined. The purpose of this study was to determine whether IGF-1 protects intestinal cells from ROS-induced apoptosis. Materials and methods: Rat intestinal epithelial (RIE)-1 cells were treated with either IGF-1 (100 nm), hydrogen peroxide (H2O2; 500 μm), or combination. Western blotting was performed to assess phosphorylation of Akt, a downstream effector of PI3-K. Cell Death Detection ELISA, DCHF, and JC-1 assays were performed to demonstrate protective effects of IGF-1. Wortmannin, an inhibitor of PI3-K, was used to show PI3-K-dependent mechanism of action for IGF-1. Results: H2O2 treatment resulted in increased intestinal epithelial cell apoptosis with intracellular ROS generation and mitochondrial membrane depolarization; IGF-1 pre-treatment attenuated this response without affecting ROS production. H2O2-induced phosphorylation of Akt was further increased with IGF-1 treatment; wortmannin abolished these effects in RIE-1 cells. Conclusions: PI3-K pathway is activated during ROS-induced intestinal epithelial cell injury; IGF-1 exerted an anti-apoptotic effect during this response by PI3-K activation. A better understanding of the exact role of IGF-1-mediated activation of PI3-K may allow us to facilitate the development of novel therapy against NEC.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalJournal of Surgical Research
Volume136
Issue number1
DOIs
StatePublished - Nov 2006
Externally publishedYes

Keywords

  • IGF-1
  • PI3-K
  • apoptosis
  • necrotizing enterocolitis
  • oxidative stress

ASJC Scopus subject areas

  • Surgery

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