Zhang Jing, Gao Yahong, Li Yuewen, Liu Dongdong, Sun Wenpeng, Liu Chuncheng, Zhao Xiujuan
School of Life Science and Technology, Inner Mongolia University of Science & Technology, Baotou 014020, China.
Inner Mongolia Key Laboratory of Functional Genome Bioinformatics, Baotou 014010, China.
Biology (Basel). 2024 Aug 24;13(9):655. doi: 10.3390/biology13090655.
Although the human body needs nickel as a trace element, too much nickel exposure can be hazardous. The effects of nickel on cells include inducing oxidative stress, interfering with DNA damage repair, and altering epigenetic modifications. Glucose metabolism and lipid metabolism are closely related to oxidative stress; however, their role in nickel-induced damage needs further study. In Institute of Cancer Research (ICR) mice, our findings indicated that nickel stress increased the levels of blood lipid indicators (triglycerides, high-density lipoprotein, and cholesterol) by about 50%, blood glucose by more than two-fold, and glycated serum protein by nearly 20%. At the same time, nickel stress increased oxidative stress (malondialdehyde) and inflammation (Interleukin 6) by about 30% in the kidney. Based on next-generation sequencing technology, we detected and analyzed differentially expressed genes in the kidney caused by nickel stress. Bioinformatics analysis and experimental verification showed that nickel inhibited the expression of genes related to lipid metabolism and the AMPK and PPAR signaling pathways. The finding that nickel induces kidney injury and inhibits key genes involved in lipid metabolism and the AMPK and PPAR signaling pathways provides a theoretical basis for a deeper understanding of the mechanism of nickel-induced kidney injury.
尽管人体需要镍作为微量元素，但过多接触镍可能有害。镍对细胞的影响包括诱导氧化应激、干扰DNA损伤修复以及改变表观遗传修饰。葡萄糖代谢和脂质代谢与氧化应激密切相关；然而，它们在镍诱导的损伤中的作用需要进一步研究。在癌症研究所（ICR）小鼠中，我们的研究结果表明，镍应激使血脂指标（甘油三酯、高密度脂蛋白和胆固醇）水平升高约50%，血糖升高两倍多，糖化血清蛋白升高近20%。同时，镍应激使肾脏中的氧化应激（丙二醛）和炎症（白细胞介素6）增加约30%。基于下一代测序技术，我们检测并分析了镍应激导致的肾脏中差异表达基因。生物信息学分析和实验验证表明，镍抑制了与脂质代谢以及AMPK和PPAR信号通路相关的基因表达。镍诱导肾脏损伤并抑制参与脂质代谢以及AMPK和PPAR信号通路的关键基因这一发现，为更深入了解镍诱导肾脏损伤的机制提供了理论依据。
