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Cellular defense against H2O2-induced apoptosis via MAP kinase-MKP-1 pathway.
Free Radic Biol Med. 2004 Apr 15; 36(8):985-93.FR

Abstract

Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is an oxidative stress-inducible gene. In this study, we investigated signaling pathways involved in oxidative stress-induced MKP-1 expression and its role in apoptosis of rat mesangial cells. Northern and Western blot analyses showed that H(2)O(2) induced expression of MKP-1 mRNA and protein in a dose-dependent manner, without affecting the stability of the transcript. H(2)O(2) induced phosphorylation of extracellular signal-regulated kinase, p38 MAP kinase, and c-Jun N-terminal kinase and consequently activated activator protein 1 (AP-1). Selective inhibitors of individual MAP kinases or a dominant-negative mutant of c-jun significantly suppressed the expression of MKP-1 by H(2)O(2). Inhibition of MKP-1 by a protein tyrosine phosphatase inhibitor (vanadate) enhanced H(2)O(2)-triggered apoptosis. Consistently, transfection with a wild-type MKP-1, but not its catalytically inactive mutant MKP-1CS, attenuated H(2)O(2)-induced apoptosis. These data elucidate, for the first time, that induction of MKP-1 by H(2)O(2) is mediated by the MAP kinase-AP-1 pathway and that the induced MKP-1 is involved in cellular defense against oxidative stress-induced apoptosis of mesangial cells.

Authors+Show Affiliations

Department of Medicine, Royal Free and University College Medical School, University College London, London, England, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15059639

Citation

Xu, Qihe, et al. "Cellular Defense Against H2O2-induced Apoptosis Via MAP kinase-MKP-1 Pathway." Free Radical Biology & Medicine, vol. 36, no. 8, 2004, pp. 985-93.
Xu Q, Konta T, Nakayama K, et al. Cellular defense against H2O2-induced apoptosis via MAP kinase-MKP-1 pathway. Free Radic Biol Med. 2004;36(8):985-93.
Xu, Q., Konta, T., Nakayama, K., Furusu, A., Moreno-Manzano, V., Lucio-Cazana, J., Ishikawa, Y., Fine, L. G., Yao, J., & Kitamura, M. (2004). Cellular defense against H2O2-induced apoptosis via MAP kinase-MKP-1 pathway. Free Radical Biology & Medicine, 36(8), 985-93.
Xu Q, et al. Cellular Defense Against H2O2-induced Apoptosis Via MAP kinase-MKP-1 Pathway. Free Radic Biol Med. 2004 Apr 15;36(8):985-93. PubMed PMID: 15059639.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cellular defense against H2O2-induced apoptosis via MAP kinase-MKP-1 pathway. AU - Xu,Qihe, AU - Konta,Tsuneo, AU - Nakayama,Kenji, AU - Furusu,Akira, AU - Moreno-Manzano,Victoria, AU - Lucio-Cazana,Javier, AU - Ishikawa,Yoshihisa, AU - Fine,Leon G, AU - Yao,Jian, AU - Kitamura,Masanori, PY - 2003/08/13/received PY - 2003/12/01/revised PY - 2004/01/15/accepted PY - 2004/4/3/pubmed PY - 2004/11/9/medline PY - 2004/4/3/entrez SP - 985 EP - 93 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 36 IS - 8 N2 - Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is an oxidative stress-inducible gene. In this study, we investigated signaling pathways involved in oxidative stress-induced MKP-1 expression and its role in apoptosis of rat mesangial cells. Northern and Western blot analyses showed that H(2)O(2) induced expression of MKP-1 mRNA and protein in a dose-dependent manner, without affecting the stability of the transcript. H(2)O(2) induced phosphorylation of extracellular signal-regulated kinase, p38 MAP kinase, and c-Jun N-terminal kinase and consequently activated activator protein 1 (AP-1). Selective inhibitors of individual MAP kinases or a dominant-negative mutant of c-jun significantly suppressed the expression of MKP-1 by H(2)O(2). Inhibition of MKP-1 by a protein tyrosine phosphatase inhibitor (vanadate) enhanced H(2)O(2)-triggered apoptosis. Consistently, transfection with a wild-type MKP-1, but not its catalytically inactive mutant MKP-1CS, attenuated H(2)O(2)-induced apoptosis. These data elucidate, for the first time, that induction of MKP-1 by H(2)O(2) is mediated by the MAP kinase-AP-1 pathway and that the induced MKP-1 is involved in cellular defense against oxidative stress-induced apoptosis of mesangial cells. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/15059639/Cellular_defense_against_H2O2_induced_apoptosis_via_MAP_kinase_MKP_1_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891584904000541 DB - PRIME DP - Unbound Medicine ER -