Higashi Tsunehito, Mai Yosuke, Mazaki Yuichi, Miwa Soichi
Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
J Biosci Bioeng. 2017 Dec;124(6):680-684. doi: 10.1016/j.jbiosc.2017.07.003. Epub 2017 Jul 25.
The unsaturated carbonyl compounds are known as the environmental pollutants. Acrolein (ACR) and methyl vinyl ketone (MVK) are representative unsaturated carbonyl compounds. ACR is contained in smoke, automobile exhaust, industrial waste, and several foods. MVK is widely used as the industrial chemical. Although ACR and MVK are highly toxic, the molecular mechanism for their cytotoxicity has been unclear. We have previously reported that ACR and MVK are major cytotoxic compounds in the gas phase of cigarette smoke, and protein kinase C (PKC) inhibitor and NADPH oxidases inhibitor partially rescued cells from ACR- or MVK-induced cell death (Noya et al., Toxicology, 314, 1-10, 2013). PKC translocation, which is hallmark for PKC activation, and cell damage were induced by treatment of cultured cells with ACR or MVK. Intracellular Ca chelator completely suppressed ACR- or MVK-induced PKC translocation to the cell membrane and cell damage, while extracellular Ca chelator had no effects on ACR- and MVK-induced cytotoxicity. These results suggest that intracellular Ca is an essential factor for cell damage caused by both PKC-dependent and PKC-independent pathways, and mobilization of Ca from intracellular Ca stores is induced by ACR or MVK.
不饱和羰基化合物是已知的环境污染物。丙烯醛（ACR）和甲基乙烯基酮（MVK）是代表性的不饱和羰基化合物。ACR存在于烟雾、汽车尾气、工业废料以及多种食物中。MVK被广泛用作工业化学品。尽管ACR和MVK具有高毒性，但其细胞毒性的分子机制尚不清楚。我们之前报道过，ACR和MVK是香烟烟雾气相中的主要细胞毒性化合物，蛋白激酶C（PKC）抑制剂和NADPH氧化酶抑制剂可部分挽救细胞免受ACR或MVK诱导的细胞死亡（Noya等人，《毒理学》，314卷，1 - 10页，2013年）。用ACR或MVK处理培养细胞可诱导PKC转位（这是PKC激活的标志）和细胞损伤。细胞内钙螯合剂完全抑制了ACR或MVK诱导的PKC向细胞膜转位以及细胞损伤，而细胞外钙螯合剂对ACR和MVK诱导的细胞毒性没有影响。这些结果表明，细胞内钙是PKC依赖性和PKC非依赖性途径导致细胞损伤的关键因素，并且ACR或MVK可诱导细胞内钙库释放钙。
