Low doses of cadmium chloride and methallothionein-1-bound cadmium display different accumulation kinetics and induce different genes in cells of the human nephron.
Low doses of cadmium chloride and methallothionein-1-bound cadmium display different accumulation kinetics and induce different genes in cells of the human nephron.
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DOI：
10.1159/000330069
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Verhulst A
中科院分区：
文献类型：
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作者：
Cucu D;D'Haese PC;De Beuf A;Verhulst A
本研究通过将原代人肾小管细胞培养物暴露于生理相关剂量的氯化镉（CdCl 2）来研究肾小管对无机镉（Cd 2+）的处理。此外，Cd 2+的细胞积累进行了比较，金属硫蛋白-1结合镉（Cd 7 MT-1）。最后，本研究的目的是探讨镉（包括Cd 2+和Cd 7 MT-1）在肾细胞中的积累对肾毒性过程相关基因表达的影响。镉浓度测定采用原子吸收光谱法。通过定量实时RT-PCR评估mRNA表达。Cd ~（2+）以浓度和时间依赖性的方式蓄积到人肾小管细胞中。此外，细胞积累的Cd 2+是不同的细胞积累的Cd 7 MT-1，指示不同的吸收途径。最后，编码抗氧化蛋白金属硫蛋白-1（MT-1）和血红素加氧酶-1（HO-1）以及促凋亡Bcl-2相关X蛋白（Bax）的基因的mRNA表达被CdCl 2上调，而不是由Cd 7 MT 1。在生理相关的镉浓度的存在下，管状积累的元素在其无机形式是不同的Cd 7 MT-1。此外，无机镉的肾小管积累诱导基因的mRNA表达，其蛋白产物可能在镉相关的肾毒性中发挥作用。
The present study was conducted to investigate the renal tubular handling of inorganic cadmium (Cd2+) by exposing primary human tubular cell cultures to physiologically relevant doses of cadmium chloride (CdCl2). Furthermore, the cellular accumulation of Cd2+ was compared to that of metallothionein-1-bound Cd (Cd7MT-1). Finally, this study aimed to investigate the effect of the accumulation of Cd (both Cd2+ and Cd7MT-1) in renal cells on the expression of genes relevant to nephrotoxic processes. Cd concentration was measured using atomic absorption spectrometry. mRNA expression was evaluated by quantitative real-time RT-PCR. Cd2+ accumulated into human tubular cells in a concentration- and time-dependent way. Furthermore, cellular accumulation of Cd2+ was different from the cellular accumulation of Cd7MT-1, indicative for different uptake routes. Finally, mRNA expression of the genes encoding the anti-oxidative proteins metallothionein-1 (MT-1) and heme-oxygenase-1 (HO-1) as well as the pro-apoptotic Bcl-2-associated X protein (Bax) were upregulated by CdCl2 and not by Cd7MT1. In the presence of physiologically relevant Cd concentrations, tubular accumulation of the element in its inorganic form is different from that of Cd7MT-1. Furthermore, the tubular accumulation of inorganic Cd induces mRNA expression of genes of which the protein products may play a role in Cd-associated renal toxicity.