Exposure of human proximal tubule cells to cd2+, zn2+, and Cu2+ induces metallothionein protein accumulation but not metallothionein isoform 2 mRNA.
Exposure of human proximal tubule cells to cd2+, zn2+, and Cu2+ induces metallothionein protein accumulation but not metallothionein isoform 2 mRNA.
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DOI：
10.1289/ehp.98106587
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发表时间：
1998-09
影响因子：
10.4
通讯作者：
Sens DA
中科院分区：
文献类型：
--
作者：
Garrett SH;Somji S;Todd JH;Sens DA
人类金属硫蛋白（MT）基因家族的组织比常用的小鼠和大鼠模型更复杂。人类MT由一个基因家族编码，该基因家族由10种功能性MT同种型和7种非功能性MT同种型组成。本研究的一个目的是确定暴露于金属的人近端小管（HPT）细胞培养物中MT蛋白的蓄积是否与从啮齿动物模型获得的知识库中预期的相似。为了实现这一目标，HPT细胞暴露于致死和亚致死浓度的Cd 2+，Zn 2+，Cu 2+，Ag 2+，Hg 2+，Pb 2+和MT蛋白水平进行了测定。结果与动物模型研究基本一致，但也有一些例外，主要是在动物模型数据库有限的地区。在明确的协议与动物模型，镉，锌，铜被证明是有效的诱导剂MT蛋白的积累。与MT蛋白表达的相似性相反，我们获得的证据表明，与动物模型和人源性细胞培养物相比，人肾MT-2基因具有独特的调控模式。在本研究中，我们确定，MT-2A mRNA不诱导HPT细胞暴露于镉或其他金属，在动物模型和其他人类细胞培养系统中的研究，其中一个高水平的MT-2 mRNA的诱导发生后，暴露于镉或锌的发现。虽然MT蛋白表达在人类和动物模型之间可能是相似的，但这一发现提供了初步证据，表明MT蛋白表达相关基因的调控在物种之间可能是不同的。
The organization of the human metallothionein (MT) gene family is more complex than the commonly used mouse and rat models. The human MTs are encoded by a family of genes consisting of 10 functional and 7 nonfunctional MT isoforms. One objective of this study was to determine if the accumulation of MT protein in cultures of human proximal tubule (HPT) cells exposed to metals is similar to that expected from the knowledge base obtained from rodent models. To accomplish this objective, HPT cells were exposed to both lethal and sublethal concentrations of Cd2+, Zn2+, Cu2+, Ag2+, Hg2+, and Pb2+ and MT protein levels were determined. The results were in general agreement with animal model studies, although there were some exceptions, mainly in areas where the animal model database was limited. In clear agreement with animal models, Cd2+, Zn2+, and Cu2+ were demonstrated to be potent inducers of MT protein accumulation. In contrast to the similarity in MT protein expression, we obtained evidence that the human renal MT-2 gene has a unique pattern of regulation compared to both animal models and human-derived cell cultures. In the present study, we determined that MT-2A mRNA was not induced by exposure of HPT cells to Cd2+ or the other metals, a finding in contrast to studies in both animal models and other human cell culture systems in which a high level of MT-2 mRNA induction occurs upon exposure to Cd2+ or Zn2+. While MT protein expression may be similar between humans and animal models, this finding provides initial evidence that regulation of the genes underlying MT protein expression may be divergent between species.