Arsenic (+3 oxidation state) methyltransferase is a specific but replaceable factor against arsenic toxicity.
Arsenic (+3 oxidation state) methyltransferase is a specific but replaceable factor against arsenic toxicity.
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DOI：
10.1016/j.toxrep.2014.08.011
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发表时间：
2014
影响因子：
--
通讯作者：
Ogra Y
中科院分区：
文献类型：
--
作者：
Tokumoto M;Kutsukake N;Yamanishi E;Katsuta D;Anan Y;Ogra Y
AS3MT催化砷的甲基化。硒和碲在AS3MT存在下没有甲基化。AS3MT基因敲除对砷的细胞毒性无影响。无机类金属，如砷（as）、锑（Sb）、硒（Se）和碲（Te），在生物群中被甲基化。特别是砷、硒和碲被甲基化并随尿液排出。生物甲基化被认为是一种解毒类金属的方法。砷（+3氧化态）甲基转移酶（AS3MT）催化砷的甲基化。然而，AS3MT是否能催化其他类金属的甲基化尚不清楚。目前也不清楚是否有其他因素代替AS3MT催化As甲基化。制备了重组人AS3MT (rhAS3MT)，并用于As、Se和Te的体外甲基化。As，而不是Se和Te，在rhAS3MT存在下特异性甲基化。然后，将靶向AS3MT的siRNA引入人肝癌（HepG2）细胞。虽然AS3MT基因敲除完全沉默了AS3MT蛋白的表达，但转染AS3MT靶向siRNA的HepG2细胞没有发现As毒性的增加。我们得出结论，AS3MT催化As的甲基化，而不是其他可生物甲基化的金属，如Se和Te。我们推测在HepG2细胞中，其他的甲基化酶也能催化As的甲基化。
AS3MT catalyzed the methylation of arsenic. Selenium and tellurium were not methylated in the presence of AS3MT. AS3MT knockdown had no effect on the cytotoxicity of arsenic. 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 in vitro 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.