Department of Biology, University of Padova, Via U. Bassi 58/B, 35131 Padova, Italy.
Department of Biomedicina Comparata e Alimentazione (BCA), University of Padova, 35131 Padova, Italy.
Int J Mol Sci. 2022 Oct 9;23(19):12001. doi: 10.3390/ijms231912001.
This work aimed to evaluate the effects of zinc (Zn) relating to cadmium (Cd)-induced toxicity and the role played by MTF-1. This transcription factor regulates the expression of genes encoding metallothioneins (MTs), some Zn transporters and the heavy chain of γ-glutamylcysteine synthetase. For this reason, two cell lines of mouse fibroblasts were used: a wild-type strain and a knockout strain to study the effects. Cells were exposed to complete medium containing: (1) 50 μM ZnSO (Zn), (2) 1 μM CdCl (Cd 1), (3) 2 μM CdCl (Cd 2), (4) 50 μM ZnSO + 1 μM CdCl (ZnCd 1) and (5) 50 μM ZnSO + 2 μM CdCl (ZnCd 2) for 4, 18 and 24 h. Following exposure, cell viability, the intracellular content of metals, glutathione (GSH) and MT and the gene expression of the two isoforms of MT was evaluated. The results obtained suggest that a lower Cd content in the co-treatments is responsible for the protection offered by Zn due to the probable competition for a common transporter. Furthermore, Zn determines an increase in GSH in co-treatments compared to treatments with Cd alone. Finally, the MTF-1 factor is essential for the expression of MT-1 but not of MT-2 nor probably for the heavy chain of γ-glutamylcysteine synthetase.
本研究旨在评估锌(Zn)与镉(Cd)诱导毒性之间的关系,以及金属转录因子 1(MTF-1)所起的作用。该转录因子调控金属硫蛋白(MTs)、某些 Zn 转运蛋白和γ-谷氨酰半胱氨酸合成酶重链的基因表达。为此,我们使用了两种小鼠成纤维细胞系:野生型和基因敲除型细胞系来进行研究。细胞暴露于含有以下成分的完全培养基中:(1)50μM 的 ZnSO(Zn),(2)1μM 的 CdCl(Cd1),(3)2μM 的 CdCl(Cd2),(4)50μM 的 ZnSO 和 1μM 的 CdCl(ZnCd1),(5)50μM 的 ZnSO 和 2μM 的 CdCl(ZnCd2),孵育 4、18 和 24 小时。暴露后,评估细胞活力、金属含量、谷胱甘肽(GSH)和 MT 以及两种 MT 同工型的基因表达。结果表明,共同处理中 Cd 含量较低是 Zn 提供保护作用的原因,这可能是由于它们对共同转运体的竞争。此外,与单独用 Cd 处理相比,Zn 处理在共同处理中导致 GSH 增加。最后,MTF-1 因子对于 MT-1 的表达是必需的,但对于 MT-2 的表达可能不是必需的,也可能不是对于 γ-谷氨酰半胱氨酸合成酶重链的表达必需的。