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JNK (c-Jun NH2-terminal kinase) is a target for antioxidants in T lymphocytes.
J Biol Chem. 1996 Oct 18; 271(42):26335-40.JB

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.

Authors+Show Affiliations

Centro de Biología Molecular y Servicio de Inmunología, Hospital de la Princesa, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid, Cantoblanco, Madrid 28006, Spain.No 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

8824287

Citation

Gómez del Arco, P, et al. "JNK (c-Jun NH2-terminal Kinase) Is a Target for Antioxidants in T Lymphocytes." The Journal of Biological Chemistry, vol. 271, no. 42, 1996, pp. 26335-40.
Gómez del Arco P, Martínez-Martínez S, Calvo V, et al. JNK (c-Jun NH2-terminal kinase) is a target for antioxidants in T lymphocytes. J Biol Chem. 1996;271(42):26335-40.
Gómez del Arco, P., Martínez-Martínez, S., Calvo, V., Armesilla, A. L., & Redondo, J. M. (1996). JNK (c-Jun NH2-terminal kinase) is a target for antioxidants in T lymphocytes. The Journal of Biological Chemistry, 271(42), 26335-40.
Gómez del Arco P, et al. JNK (c-Jun NH2-terminal Kinase) Is a Target for Antioxidants in T Lymphocytes. J Biol Chem. 1996 Oct 18;271(42):26335-40. PubMed PMID: 8824287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - JNK (c-Jun NH2-terminal kinase) is a target for antioxidants in T lymphocytes. AU - Gómez del Arco,P, AU - Martínez-Martínez,S, AU - Calvo,V, AU - Armesilla,A L, AU - Redondo,J M, PY - 1996/10/18/pubmed PY - 1996/10/18/medline PY - 1996/10/18/entrez SP - 26335 EP - 40 JF - The Journal of biological chemistry JO - J Biol Chem VL - 271 IS - 42 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/8824287/JNK__c_Jun_NH2_terminal_kinase__is_a_target_for_antioxidants_in_T_lymphocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)39912-5 DB - PRIME DP - Unbound Medicine ER -