title: Oxidative stress-induced intestinal epithelial cell apoptosis is mediated by p38 MAPK.
abstract: Free oxygen radicals are involved in the pathogenesis of necrotizing enterocolitis (NEC) in premature infants. The stress-activated p38 mitogen-activated protein kinase (MAPK) has been implicated in gut injury. Here, we found that phosphorylated p38 was detected primarily in the villus tips of normal intestine, whereas it was expressed in the entire mucosa in NEC. H(2)O(2) treatment resulted in a rapid phosphorylation of p38 MAPK and subsequent apoptosis of rat intestinal epithelial (RIE)-1 cells; this induction was attenuated by treatment with SB203580, a selective p38 MAPK inhibitor, or transfection with p38alpha siRNA. Moreover, SB203580 also blocked H(2)O(2)-induced PKC activation. In contrast, the PKC inhibitor (GF109203x) did not affect p38 activation, indicating that p38 MAPK activation occurs upstream of PKC activation in H(2)O(2)-induced apoptosis. H(2)O(2) treatment also decreased mitochondrial membrane potential; pretreatment with SB203580 attenuated this response. Our study demonstrates that the p38 MAPK/PKC pathway plays an important role as a pro-apoptotic cellular signaling during oxidative stress-induced intestinal epithelial cell injury.
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qingding
authors.initials: Q
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Mark Evers
authors.forename: Dai H
authors.initials: DH
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases