Arsenic: signal transduction, transcription factor, and biotransformation involved in cellular response and toxicity.
Arsenic is a naturally occurring metalloid that causes oxidative stress. Exposure of humans, experimental animals, and cultured cells to arsenic results in a variety of diverse health effects, dysfunction of critical enzymes, and cell damage. In this context, one area of arsenic study has been the role of its metabolism. Like organic chemicals, arsenic undergoes reduction, methylation, and glutathione conjugation to yield polar metabolites that are substrates for transporters. These events suggest that transcription factor(s) controlling the upregulation of antioxidant proteins, Phase II xenobiotic-metabolizing enzymes, and Phase III transporters should affect arsenic-mediated oxidative stress and the steady-state level of arsenic in the cells. In this review, we summarize recent progress in arsenic toxicity in terms of disrupted signal transduction cascades, the transcription factors involved, and arsenic biotransformation, including a novel pathway.
Kumagai
Yoshito
Y
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. yk-em-tu@md.tsukuba.ac.jp
Sumi
Daigo
D
D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D001711:Biotransformation; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000187:drug effects; D009569:Nitric Oxide; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000187:drug effects*
D051267:NF-E2-Related Factor 2; D014157:Transcription Factors; D009569:Nitric Oxide; D001151:Arsenic