Zinc, oxidant-triggered cell signaling, and human health

Patricia I Oteiza, Gerardo G. Mackenzie

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


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-κB 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 H2O2, 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-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 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.

Original languageEnglish (US)
Pages (from-to)245-255
Number of pages11
JournalMolecular Aspects of Medicine
Issue number4-5 SPEC. ISS.
StatePublished - Aug 2005


  • AP-1
  • Cell signaling
  • NF-κB
  • Oxidative stress
  • Zinc
  • Zinc deficiency

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine


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