NF-kappaB, AP-1, Zinc-deficiency and aging.
Zinc (Zn) deficiency, a frequent condition in human population especially in aged persons, induces oxidative stress and subsequently activates/inhibits oxidant-sensitive transcription factors that can affect cell function, proliferation and survival leading to disease. Zn deficiency-triggered oxidative stress could affect cell signalling, including transcription factors containing Zn finger motifs and other oxidant-sensitive transcription factors such as nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1). AP-1 can be activated in Zn deficiency that can occur secondary to an increase in cellular H(2)O(2), followed by activation of MAPKs p38 and JNK. Similarly, the cytosolic steps of the NF-kappaB cascade are activated by oxidants in Zn deficiency. However, an impaired nuclear transport of the active transcription factor leads to a low expression of NF-kappaB-dependent genes that could be involved in multiple steps of Zn deficiency associated pathology. We present here evidence that, following experimental depletion of Zn, both NF-kappaB and AP-1 signallings are altered in primary T cells isolated from young and elderly healthy individuals under CD3/CD28 costimulation. A supplementation of Zn restored both NF-kappaB and AP-1 activation in CD3/CD28 costimulated T cells from young, but not from elderly, healthy individuals, indicating that the Zn deficiency is only one component of a more complex mechanism involved in immunosenescence. In this review we summarize our present knowledge on NF-kappaB and AP-1 activation and underline the role of Zn in this process, especially in the context of Zn deficiency observed in aged persons leading to immunosenescence.
Herbein
Georges
G
Department of Virology, IFR 133, EA 3186, Franche-Comte University, F-25030, Besancon, France. gherbein@chu-besancon.fr
Varin
A
A
Fulop
Tamas
T
D000375:Aging / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D016922:Cellular Senescence; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D015032:Zinc