Signaling from toxic metals to NF-kappaB and beyond: not just a matter of reactive oxygen species.
The nuclear factor kappa B (NF-kappaB) family of transcription factors controls expression of a number of early response genes associated with inflammatory responses, cell growth, cell cycle progression, and neoplastic transformation. These genes include a multitude of cytokines, chemokines, adhesion molecules, immune receptors, stress proteins, apoptotic or anti-apoptotic regulators, and several oncogenes. Accumulating evidence indicates that a variety of toxic metals are able to affect the activation or activity of NF-kappaB, but the molecular mechanisms involved in this process remain largely unknown. The signaling pathways mediating cytokine- or microorganism-induced NF-kappaB activation have been well established recently. Whether the same signaling systems are involved in metal-induced NF-kappaB activation, however, is unclear. In the present review, we have attempted to evaluate and update the possible mechanisms of metal signals on the activation and function of NF-kappaB.
Chen
Fei
F
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA. lfd3@cdc.gov
Shi
Xianglin
X
D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D019216:Metals, Heavy / Q000009:adverse effects* / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000494:pharmacology*; D018384:Oxidative Stress; D010770:Phosphotransferases / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000009:adverse effects; D015398:Signal Transduction
D016207:Cytokines; D019216:Metals, Heavy; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D010770:Phosphotransferases