Zinc, oxidant-triggered cell signaling, and human health.
Zinc (Zn) deficiency, a frequent condition in human populations, 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 signaling, including: (1) transcription factors containing Zn finger motifs, and (2) other oxidant-sensitive transcription factors (NF-kappaB and AP-1). The Zn finger motif in the Zn finger transcription factors is mainly a DNA binding domain. Cysteine residues coordinate the Zn ion folding structural domains that participate in intermolecular interactions. Oxidative stress can impair the DNA-binding activity of Zn finger transcription factor, by oxidizing the cysteine residues and therefore altering the secondary structure of the protein. AP-1 is generally 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. The role of AP-1 in Zn deficiency-associated pathology remains to be established. 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 aspects of Zn deficiency associated pathology. In summary, Zn deficiency induces oxidative stress that can both, lead to tissue oxidative damage and/or to the modulation of select signaling cascades. Their role in the pathology of Zn deficiency remains to be defined.
Oteiza
Patricia I
PI
Department of Nutrition, University of California, Davis, CA 95616, USA. poteiza@ucdavis.edu
Mackenzie
Gerardo G
GG
D006262:Health; D006801:Humans; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
D016877:Oxidants; D014157:Transcription Factors; D015032:Zinc