Oxidative stress-induced intestinal epithelial cell apoptosis is mediated by p38 MAPK

Yuning Zhou1, Qingding Wang, B Mark Evers

  • 1Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555, USA.

Insights

Oxidative stress triggers p38 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) activation, leading to apoptosis in intestinal cells. Inhibiting p38 MAPK protects against this injury, suggesting a therapeutic target for necrotizing enterocolitis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Gastroenterology

Background:

  • Necrotizing enterocolitis (NEC) involves free oxygen radicals and gut injury.
  • Stress-activated p38 mitogen-activated protein kinase (MAPK) is implicated in intestinal damage.

Purpose of the Study:

  • To investigate the role of p38 MAPK and protein kinase C (PKC) in oxidative stress-induced intestinal epithelial cell apoptosis.
  • To determine the signaling pathway involved in H(2)O(2)-induced intestinal injury.

Main Methods:

  • Examined p38 MAPK phosphorylation in normal and NEC intestinal tissues.
  • Induced oxidative stress with H(2)O(2) in rat intestinal epithelial cells.
  • Utilized p38 MAPK inhibitors (SB203580) and siRNA, and a PKC inhibitor (GF109203x).
  • Assessed apoptosis and mitochondrial membrane potential.

Main Results:

  • Phosphorylated p38 MAPK was elevated in NEC mucosa compared to normal intestine.
  • H(2)O(2) induced p38 MAPK and PKC activation, leading to apoptosis and decreased mitochondrial membrane potential.
  • SB203580 attenuated H(2)O(2)-induced apoptosis, PKC activation, and mitochondrial dysfunction.
  • p38 MAPK activation occurred upstream of PKC activation.

Conclusions:

  • The p38 MAPK/PKC pathway is crucial for oxidative stress-induced intestinal epithelial cell apoptosis.
  • Targeting the p38 MAPK pathway may offer a therapeutic strategy for NEC and other intestinal injuries.

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