Wang Hecheng, Sun Shibo, Ren Yan, Yang Rui, Guo Jianli, Zong Yu, Zhang Qiuxian, Zhao Jing, Zhang Wei, Xu Weiping, Guan Shui, Xu Jianqiang
School of Life and Pharmaceutical Sciences (LPS) & Panjin Institute of Industrial Technology (PIIT), Dalian University of Technology, Panjin, 124221, China.
School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453000, China.
Biol Trace Elem Res. 2023 Jan;201(1):139-148. doi: 10.1007/s12011-022-03117-6. Epub 2022 Jan 23.
Cadmium (Cd) as a ubiquitous toxic heavy metal in the environment, causes severe hazards to human health, such as cellular stress and organ injury. Selenium (Se) was reported to reduce Cd toxicity and the mechanisms have been intensively studied so far. However, it is not yet crystal clear whether the protective effect of Se against Cd-induced cytotoxicity is related to selenoproteins in nerve cells or not. In this study, we found that Cd inhibited selenoprotein thioredoxin reductase 1 (TrxR1; TXNRD1) and decreased the expression level of TrxR1, resulting in cellular oxidative stress, and Se supplements ameliorated Cd-induced cytotoxicity in SH-SY5Y cells. Mechanistically, the detoxification of Se against Cd is attributed to the increase of the cellular TrxR activity and upregulated TrxR1 protein level, culminating in strengthened antioxidant capacity. Results showed that Se supplements attenuated the ROS production and apoptosis in SH-SY5Y cells, and significantly mitigated Cd-induced SH-SY5Y cell death. This study may be a valuable reference for shedding light on the mechanism of Cd-induced cytotoxicity and the role of TrxR1 in Se-mitigated cytotoxicity of Cd in neuroblast cells, which may be helpful for understanding the therapeutic potential of Cd and Se in treating or preventing neurodegenerative diseases, like Alzheimer's disease (AD) and Parkinson's disease (PD).
镉（Cd）作为环境中普遍存在的有毒重金属，对人类健康造成严重危害，如细胞应激和器官损伤。据报道，硒（Se）可降低镉的毒性，目前对其作用机制已进行了深入研究。然而，硒对镉诱导的细胞毒性的保护作用是否与神经细胞中的硒蛋白有关，目前尚不清楚。在本研究中，我们发现镉抑制硒蛋白硫氧还蛋白还原酶1（TrxR1；TXNRD1）并降低TrxR1的表达水平，导致细胞氧化应激，而补充硒可改善镉诱导的SH-SY5Y细胞毒性。从机制上讲，硒对镉的解毒作用归因于细胞TrxR活性的增加和TrxR1蛋白水平的上调，最终增强了抗氧化能力。结果表明，补充硒可减轻SH-SY5Y细胞中的活性氧生成和凋亡，并显著减轻镉诱导的SH-SY5Y细胞死亡。本研究可能为阐明镉诱导的细胞毒性机制以及TrxR1在硒减轻神经母细胞瘤细胞镉细胞毒性中的作用提供有价值的参考，这可能有助于理解镉和硒在治疗或预防神经退行性疾病（如阿尔茨海默病（AD）和帕金森病（PD））方面的治疗潜力。
