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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.

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Authors+Show Affiliations

Xu Q
Department of Medicine, Royal Free and University College Medical School, University College London, London, England, United Kingdom.
Konta T
No affiliation info available
Nakayama K
No affiliation info available
Furusu A
No affiliation info available
Moreno-Manzano V
No affiliation info available
Lucio-Cazana J
No affiliation info available
Ishikawa Y
No affiliation info available
Fine LG
No affiliation info available
Yao J
No affiliation info available
Kitamura M
No affiliation info available

MeSH

AnimalsApoptosisBlotting, NorthernBlotting, WesternCell Cycle ProteinsDose-Response Relationship, DrugDual Specificity Phosphatase 1Enzyme InhibitorsFree RadicalsGlomerular MesangiumHydrogen PeroxideImmediate-Early ProteinsJNK Mitogen-Activated Protein KinasesMAP Kinase Signaling SystemMaleMitogen-Activated Protein KinasesOxidantsOxidative StressPhosphoprotein PhosphatasesProtein Phosphatase 1Protein Tyrosine PhosphatasesRNA, MessengerRatsRats, Sprague-DawleyReactive Oxygen SpeciesSignal TransductionTime FactorsTransfectionp38 Mitogen-Activated Protein Kinases

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 -
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