2.50
Hdl Handle:
http://hdl.handle.net/2436/7739
Title:
JNK (c-Jun NH2-terminal kinase) is a target for antioxidants in T lymphocytes.
Authors:
Gómez del Arco, Pablo; Martínez-Martínez, Sara; Calvo, Victor; Armesilla, Angel Luis; Redondo, Juan Miguel
Abstract:
AP-1 has been shown to behave as a redox-sensitive transcription factor that can be activated by both oxidant and antioxidant stimuli. However, the mechanisms involved in the activation of AP-1 by antioxidants are largely unknown. In this study we show that the structurally unrelated antioxidant agents pyrrolidine dithiocarbamate (PDTC), butylated hydroxyanisole, and Nacetylcysteine activated JNK (c-Jun NH2-terminal kinase) in Jurkat T cells. This activation differed substantially from that mediated by phorbol 12-myristate 13-acetate (PMA) and Ca2+ ionophore or produced by costimulation with antibodies against the T cell receptor-CD3 complex and to CD28. The activation of JNK by classical T cell stimuli was transient, whereas that mediated by PDTC and butylated hydroxyanisole (but not N-acetylcysteine) was sustained. The kinetics of JNK activation correlated with the expression of c-jun which was transient after stimulation with PMA plus ionophore and prolonged in response to PDTC, which also transiently induced c-fos. In addition, JNK activation by PMA plus ionophore was sensitive to inhibitors of signaling pathways involving Ca2+, protein kinase C, and tyrosine phosphorylation, which failed to inhibit the activation mediated by PDTC. Transfection of trans-dominant negative expression vectors of ras and raf, together with AP-1-dependent reporter constructs, as well as Western blot analysis using anti-ERK (extracellular signal-regulated kinase) antibodies, indicated that the Ras/Raf/ERK pathway did not appear to mediate the effect of the antioxidant. However, the combined treatment with PDTC and PMA, two agents that synergize on AP-1 activation, resulted in the persistent phosphorylation of ERK-2. In conclusion, our results identify JNK as a target of antioxidant agents which can be regulated differentially under oxidant and antioxidant conditions.
Citation:
The Journal of Biological Chemistry, 271(42): 26335-26340
Publisher:
American Society for Biochemistry and Molecular Biology
Issue Date:
1996
URI:
http://hdl.handle.net/2436/7739
PubMed ID:
8824287
Additional Links:
http://www.jbc.org/cgi/reprint/271/42/26335
Submitted date:
2007-01-24
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
Molecular Pharmacology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorGómez del Arco, Pablo-
dc.contributor.authorMartínez-Martínez, Sara-
dc.contributor.authorCalvo, Victor-
dc.contributor.authorArmesilla, Angel Luis-
dc.contributor.authorRedondo, Juan Miguel-
dc.date.accessioned2007-01-24T13:53:34Z-
dc.date.available2007-01-24T13:53:34Z-
dc.date.issued1996-
dc.date.submitted2007-01-24-
dc.identifier.citationThe Journal of Biological Chemistry, 271(42): 26335-26340en
dc.identifier.issn0021-9258-
dc.identifier.pmid8824287-
dc.identifier.urihttp://hdl.handle.net/2436/7739-
dc.description.abstractAP-1 has been shown to behave as a redox-sensitive transcription factor that can be activated by both oxidant and antioxidant stimuli. However, the mechanisms involved in the activation of AP-1 by antioxidants are largely unknown. In this study we show that the structurally unrelated antioxidant agents pyrrolidine dithiocarbamate (PDTC), butylated hydroxyanisole, and Nacetylcysteine activated JNK (c-Jun NH2-terminal kinase) in Jurkat T cells. This activation differed substantially from that mediated by phorbol 12-myristate 13-acetate (PMA) and Ca2+ ionophore or produced by costimulation with antibodies against the T cell receptor-CD3 complex and to CD28. The activation of JNK by classical T cell stimuli was transient, whereas that mediated by PDTC and butylated hydroxyanisole (but not N-acetylcysteine) was sustained. The kinetics of JNK activation correlated with the expression of c-jun which was transient after stimulation with PMA plus ionophore and prolonged in response to PDTC, which also transiently induced c-fos. In addition, JNK activation by PMA plus ionophore was sensitive to inhibitors of signaling pathways involving Ca2+, protein kinase C, and tyrosine phosphorylation, which failed to inhibit the activation mediated by PDTC. Transfection of trans-dominant negative expression vectors of ras and raf, together with AP-1-dependent reporter constructs, as well as Western blot analysis using anti-ERK (extracellular signal-regulated kinase) antibodies, indicated that the Ras/Raf/ERK pathway did not appear to mediate the effect of the antioxidant. However, the combined treatment with PDTC and PMA, two agents that synergize on AP-1 activation, resulted in the persistent phosphorylation of ERK-2. In conclusion, our results identify JNK as a target of antioxidant agents which can be regulated differentially under oxidant and antioxidant conditions.en
dc.format.extent494703 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.urlhttp://www.jbc.org/cgi/reprint/271/42/26335en
dc.subjectJNKen
dc.subjectc-Jun NH2-terminal kinaseen
dc.subjectAntioxidantsen
dc.subjectT Lymphocytesen
dc.titleJNK (c-Jun NH2-terminal kinase) is a target for antioxidants in T lymphocytes.en
dc.typeArticleen
dc.format.digYES-
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