Tokumoto Maki, Kutsukake Natsuko, Yamanishi Erika, Katsuta Daiki, Anan Yasumi, Ogra Yasumitsu
Laboratory of Chemical Toxicology and Environmental Health, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida 194-8543, Tokyo, Japan.
Toxicol Rep. 2014 Aug 29;1:589-595. doi: 10.1016/j.toxrep.2014.08.011. eCollection 2014.
Inorganic metalloids, such as arsenic (As), antimony (Sb), selenium (Se), and tellurium (Te), are methylated in biota. In particular, As, Se, and Te are methylated and excreted in urine. The biomethylation is thought to be a means to detoxify the metalloids. The methylation of As is catalyzed by arsenic (+3 oxidation state) methyltransferase (AS3MT). However, it is still unclear whether AS3MT catalyzes the methylation of the other metalloids. It is also unclear whether other factors catalyze the As methylation instead of AS3MT. Recombinant human AS3MT (rhAS3MT) was prepared and used in the methylation of As, Se, and Te. As, but not Se and Te, was specifically methylated in the presence of rhAS3MT. Then, siRNA targeting AS3MT was introduced into human hepatocarcinoma (HepG2) cells. Although AS3MT protein expression was completely silenced by the gene knockdown, no increase in As toxicity was found in the HepG2 cells transfected with AS3MT-targeting siRNA. We conclude that AS3MT catalyzes the methylation of As and not other biomethylatable metalloids, such as Se and Te. We speculate that other methylation enzyme(s) also catalyze the methylation of As in HepG2 cells.
无机类金属，如砷（As）、锑（Sb）、硒（Se）和碲（Te），在生物群中会发生甲基化。特别是，砷、硒和碲会甲基化并通过尿液排出。生物甲基化被认为是一种使类金属解毒的方式。砷的甲基化由砷（+3氧化态）甲基转移酶（AS3MT）催化。然而，AS3MT是否催化其他类金属的甲基化仍不清楚。也不清楚是否有其他因素而非AS3MT催化砷的甲基化。制备了重组人AS3MT（rhAS3MT）并将其用于砷、硒和碲的甲基化反应。在rhAS3MT存在的情况下，只有砷发生了特异性甲基化，而硒和碲没有。然后，将靶向AS3MT的小干扰RNA（siRNA）导入人肝癌（HepG2）细胞。尽管基因敲低使AS3MT蛋白表达完全沉默，但在用靶向AS3MT的siRNA转染的HepG2细胞中未发现砷毒性增加。我们得出结论，AS3MT催化砷的甲基化，而不催化其他可生物甲基化的类金属，如硒和碲。我们推测，其他甲基化酶也在HepG2细胞中催化砷的甲基化。
