Valverde M, Rosales-Cruz P, Torrejon-Gonzalez E, Ponce-Ortiz A, Rodriguez-Sastre M A, Rojas E
Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, Mexico, Mexico.
Oxid Med Cell Longev. 2024 Dec 18;2024:6983256. doi: 10.1155/omcl/6983256. eCollection 2024.
Occupational exposure to arsenic (As), cadmium (Cd), and lead (Pb) affects many sectors, necessitating research to understand their transformation mechanisms. In this study, we characterized the process of epithelial-mesenchymal transition (EMT) in a rat hepatic epithelial cell line with decreased expression of catalase and glutamate cysteine ligase catalytic (GCLC) subunit that was exposed to a mixture of As, Cd, and Pb at equimolar occupational exposure concentrations. We evaluated the expression of genes and proteins involved in EMT. Our findings revealed that cells with a decreased antioxidant barrier showed a decreased expression and abundance of epithelial genes when exposed to a mixture of metals. Additionally, we observed alterations in the expression of transcription factors (TFs) associated with EMT and an increase in the expression and abundance of mesenchymal genes. Specifically, we found that E-cadherin expression decreased by ~50% at both the gene and protein levels. In contrast, the expression of , , and genes increased by ~70%, whereas their corresponding protein levels increased by nearly 100%. Furthermore, the TFs zinc finger e-box binding homeobox 1 and snail family transcriptional repressor 1 showed a 30% increase in gene expression and an ~80% increase in protein expression. These changes enable the cells to acquire migratory capabilities. Our results confirmed that exposure to this mixture of As, Cd, and Pb can induce EMT in cells with a decreased antioxidant barrier.
职业性接触砷（As）、镉（Cd）和铅（Pb）会影响多个行业，因此有必要开展研究以了解它们的转化机制。在本研究中，我们对过氧化氢酶和谷氨酸半胱氨酸连接酶催化亚基（GCLC）表达降低的大鼠肝上皮细胞系中的上皮-间质转化（EMT）过程进行了表征，该细胞系暴露于等摩尔职业接触浓度的As、Cd和Pb混合物中。我们评估了参与EMT的基因和蛋白质的表达。我们的研究结果表明，抗氧化屏障降低的细胞在暴露于金属混合物时，上皮基因的表达和丰度降低。此外，我们观察到与EMT相关的转录因子（TFs）表达发生改变，间充质基因的表达和丰度增加。具体而言，我们发现E-钙黏蛋白在基因和蛋白质水平上的表达均下降了约50%。相比之下， 、 和 基因的表达增加了约70%，而它们相应的蛋白质水平增加了近100%。此外，转录因子锌指E盒结合同源框1和蜗牛家族转录抑制因子1的基因表达增加了30%，蛋白质表达增加了约80%。这些变化使细胞获得迁移能力。我们的结果证实，暴露于这种As、Cd和Pb的混合物可在抗氧化屏障降低的细胞中诱导EMT。
