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NF-κB, AP-1, Zinc-deficiency and aging

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Abstract

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-κB) and activator protein-1 (AP-1). AP-1 can be activated in Zn deficiency that can occur secondary to an increase in cellular H2O2, followed by activation of MAPKs p38 and JNK. Similarly, the cytosolic steps of the NF-κB 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-κB-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-κB 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-κB 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-κB 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.

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Acknowledgements

This work was partly supported by a grant-in aid from the Canadian Institute of Health Research (No. 63149) and ZINCAGE Project (EU Contract No. FOOD-CT-2003-506850).

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Authors and Affiliations

  1. Department of Virology, IFR 133, EA 3186, Franche-Comte University, F-25030, Besancon, France

    Georges Herbein & A. Varin

  2. Département de Médecine, Centre de Recherche sur le Vieillissement, Service de Gériatrie, Université de Sherbrooke, Sherbrooke, Que., Canada

    Tamas Fulop

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  1. Georges Herbein
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  2. A. Varin
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  3. Tamas Fulop
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Corresponding authors

Correspondence to Georges Herbein or Tamas Fulop.

Additional information

Presented at the ZincAge Conference, Madrid, February 10–13, 2006.

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Herbein, G., Varin, A. & Fulop, T. NF-κB, AP-1, Zinc-deficiency and aging. Biogerontology 7, 409–419 (2006). https://doi.org/10.1007/s10522-006-9056-4

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