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

Yuning Zhou; Qingding Wang; B. Mark Evers; Dai H. Chung

doi:10.1016/j.bbrc.2006.09.103

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

Yuning Zhou, Qingding Wang, B. Mark Evers, Dai H. Chung

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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. H₂O₂ 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 p38α siRNA. Moreover, SB203580 also blocked H₂O₂-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 H₂O₂-induced apoptosis. H₂O₂ 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.

Original language	English
Pages (from-to)	860-865
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	350
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2006.09.103
State	Published - Dec 1 2006

Bibliographical note

Funding Information:
The authors thank Karen Martin for manuscript preparation and Tatsuo Uchida for assistance with statistical analysis. This work was supported by Grants RO1 DK61470, RO1 DK48498, and PO1 DK35608 from the National Institutes of Health and 8580 from the Shriners Burns Hospital.

Keywords

Apoptosis
Intestinal epithelial cell injury
NEC
Oxidative stress
p38 MAPK

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2006.09.103

Cite this

@article{a2e7c927bfba46a6bc7bb5576acd5a22,

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. H2O2 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 p38α siRNA. Moreover, SB203580 also blocked H2O2-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 H2O2-induced apoptosis. H2O2 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.",

keywords = "Apoptosis, Intestinal epithelial cell injury, NEC, Oxidative stress, p38 MAPK",

author = "Yuning Zhou and Qingding Wang and {Mark Evers}, B. and Chung, {Dai H.}",

note = "Funding Information: The authors thank Karen Martin for manuscript preparation and Tatsuo Uchida for assistance with statistical analysis. This work was supported by Grants RO1 DK61470, RO1 DK48498, and PO1 DK35608 from the National Institutes of Health and 8580 from the Shriners Burns Hospital.",

year = "2006",

month = dec,

day = "1",

doi = "10.1016/j.bbrc.2006.09.103",

language = "English",

volume = "350",

pages = "860--865",

number = "4",

}

TY - JOUR

T1 - Oxidative stress-induced intestinal epithelial cell apoptosis is mediated by p38 MAPK

AU - Zhou, Yuning

AU - Wang, Qingding

AU - Mark Evers, B.

AU - Chung, Dai H.

N1 - Funding Information: The authors thank Karen Martin for manuscript preparation and Tatsuo Uchida for assistance with statistical analysis. This work was supported by Grants RO1 DK61470, RO1 DK48498, and PO1 DK35608 from the National Institutes of Health and 8580 from the Shriners Burns Hospital.

PY - 2006/12/1

Y1 - 2006/12/1

N2 - 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. H2O2 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 p38α siRNA. Moreover, SB203580 also blocked H2O2-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 H2O2-induced apoptosis. H2O2 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.

AB - 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. H2O2 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 p38α siRNA. Moreover, SB203580 also blocked H2O2-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 H2O2-induced apoptosis. H2O2 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.

KW - Apoptosis

KW - Intestinal epithelial cell injury

KW - NEC

KW - Oxidative stress

KW - p38 MAPK

UR - http://www.scopus.com/inward/record.url?scp=33750058573&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750058573&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2006.09.103

DO - 10.1016/j.bbrc.2006.09.103

M3 - Article

C2 - 17034759

AN - SCOPUS:33750058573

SN - 0006-291X

VL - 350

SP - 860

EP - 865

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this