日本毒性学会学術年会
第44回日本毒性学会学術年会
セッションID: S20-4
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シンポジウム20 A new era: Exposome and toxicology
Is environmental electrophile an essential item for exposome?
*熊谷 嘉人
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会議録・要旨集 フリー

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Included among the many environmental electrophiles are aromatic hydrocarbon quinones formed during combustion of gasoline, crotonaldehyde in tobacco smoke, methylmercury accumulated in fish, cadmium contaminated in rice, and acrylamide in baked foods. Although these reactive species exhibit different chemical structures, the common molecular target is protein nucleophiles. We found that these environmental electrophiles can covalently modify sensor proteins with reactive cysteine residues forming their adducts, resulting in activation of cellular redox signal transduction pathways (PTP1B/EGFR signal, Keap1/Nrf2 pathway, HSP90/HSF1 signal and PTEN/Akt signal) involved in cell survival, cell proliferation, and adaptive response. However, higher concentrations of electrophiles disrupt such signaling by nonselective covalent modification of cellular proteins, leading to cell damage. Persulfide/polysulfides produced by various enzymes appear to capture environmental electrophiles because of the formation of their sulfur adducts without electrophilicity. We therefore speculate that persulfide/polysulfides are candidates for the regulation of redox signal transduction pathways and toxicity during exposure to environmental electrophiles. In this symposium, we will discuss whether or not environmental electrophiles are critical item for exposome study.
References
1. Kumagai Y and Abiko Y. Chem Res Toxicol 30: 203-219, 2017.
2. Abiko Y et al. Free Radic Biol Med 104: 118-128, 2017.
3. Shinkai Y et al. Toxicol Sci in press, 2017.
4. Abiko Y et al. Chem Res Toxicol 28: 1301-1306, 2015.
5. Kumagai Y et al. Annu Rev Pharmacol Toxicol 52: 221-247, 2012.

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