Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University.
Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
J Toxicol Sci. 2020;45(12):801-806. doi: 10.2131/jts.45.801.
Metallothionein (MT) is an inducible protein with cytoprotective activity against heavy metals such as cadmium, zinc, and copper. MT-1 and MT-2 are the isoforms of MT induced by and bind the heavy metals. Bovine aortic endothelial cells contain three types of MT genes, namely, MT-1A, MT-1E, and MT-2A; however, the associated protein expression of these MT isoforms has not been identified. In the present study, the expression of MT subisoform proteins in cells treated with cadmium chloride was identified using a high-performance liquid chromatography-inductively coupled plasma-mass spectrometry system. It was revealed that: (1) transcriptional induction of MT-1A by cadmium was markedly more sensitive than that of MT-1E/2A; (2) MT-1A and MT-2A proteins were the predominant MT subisoforms induced by cadmium; and (3) there might be differentiation in the functions of MT-1 and MT-2 against cadmium cytotoxicity, although the actual roles of the MT isoforms in the cells were not distinct. This is the first study to show the differential induction of isoforms of MT proteins in vascular endothelial cells by cadmium.
金属硫蛋白（MT）是一种具有细胞保护活性的诱导蛋白，可抵抗镉、锌和铜等重金属。MT-1 和 MT-2 是由重金属诱导并与之结合的 MT 同工型。牛主动脉内皮细胞包含三种类型的 MT 基因，即 MT-1A、MT-1E 和 MT-2A；然而，这些 MT 同工型的相关蛋白表达尚未确定。在本研究中，使用高效液相色谱-电感耦合等离子体质谱系统鉴定了氯化镉处理细胞中 MT 亚基蛋白的表达。结果表明：（1）镉对 MT-1A 的转录诱导比 MT-1E/2A 更为敏感；（2）MT-1A 和 MT-2A 蛋白是镉诱导的主要 MT 亚基同工型；（3）尽管 MT 同工型在细胞中的实际作用并不明显，但 MT-1 和 MT-2 在对抗镉细胞毒性方面的功能可能存在差异。这是首次表明镉可诱导血管内皮细胞中 MT 蛋白同工型的差异诱导。
