JNK (c-Jun NH2-terminal kinase) is a target for antioxidants in T lymphocytes.
Authors
Gómez del Arco, PabloMartínez-Martínez, Sara
Calvo, Victor
Armesilla, Angel
Redondo, Juan Miguel
Issue Date
1996-10-18Submitted date
2007-01-24
Metadata
Show full item recordAbstract
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
Gómez Arco, P., Martínez-Martínez, S., Calvo, V., Armesilla, A.L. and Redondo, J.M. (1996) JNK (c-Jun NH2-terminal Kinase) Is a Target for Antioxidants in T Lymphocytes. Journal of Biological Chemistry, 271(42), pp. 26335-26340.PubMed ID
8824287Additional Links
https://www.sciencedirect.com/science/article/pii/S0021925818399125Type
Journal articleLanguage
enISSN
0021-9258ae974a485f413a2113503eed53cd6c53
10.1074/jbc.271.42.26335