Lead exposure induces neuronal apoptosis via NFκB p65/RBBP4/Survivin signaling pathway

• Published in: Toxicology (Amsterdam) 2023-11, Vol.499, p.153654-153654, Article 153654
• Main Authors: Chen, Hui, Zhang, Wei, Luo, Song, Li, Yanshu, Zhu, Qian, Xia, Yongli, Tan, Hong, Bian, Ying, Li, Yaobing, Ma, Jianmin, Chen, Wei, Luo, Xietian, Zhu, Gaochun
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; exposure models; Female; females; heavy metals; hippocampus; histones; lead; Lead - toxicity; neurons; NF-kappa B - metabolism; NFκB p65; PC12 Cells; Pregnancy; pro-apoptotic proteins; Rats; RBBP4; RNA, Messenger - metabolism; Signal Transduction; Survivin; Survivin - metabolism
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2023.153654

Lead (Pb), as a heavy metal that is easily exposed in daily life, can cause damage to various systems of body. Apoptosis is an autonomous cell death process regulated by genes in order to maintain the stability of internal environment, which plays an important role in the development of nervous system. RB binding protein 4 (RBBP4) is one of the core histone binding subunits and is closely related to the apoptosis process of nervous system cells. However, it is not known whether RBBP4 can regulate neuronal apoptosis in lead-exposed environments. We exposed PC12 cells to 0μM (control group), 1μM, and 100μM PbAc for 24hours to obtain cell samples. The female rats ingested drinking water containing 0, 0.5g/L, and 2.0g/L PbAc from the first day of pregnancy to three weeks after delivery to obtain hippocampal tissue samples from mammary rats. The results of TUNEL showed that lead exposure promoted the onset of apoptosis in cells and hippocampus. The mRNA and protein levels of the apoptosis-related protein Survivin were significantly reduced in the lead-exposed group compared to the control group. In addition, we found that lead exposure reduces the mRNA and protein levels of RBBP4 in PC12 cells and hippocampus, and increases the mRNA and protein levels of NFκB p65. Moreover, inhibiting NFκB p65 can reverse the decrease in RBBP4 expression in the lead exposure model. Overexpression of RBBP4 increased Survivin expression and reduced apoptosis induced by lead exposure. This suggests that lead exposure induces apoptosis through the NFκB p65/RBBP4/Survivin signaling pathway. •New molecular mechanism of neuronal apoptosis induced by lead exposure.•RBBP4 function and its regulation of the apoptosis-associated protein Survivin have been explored in a lead exposure model.•The demonstration that NFκB p65 can inhibit the expression of RBBP4 in a lead exposure model may provide a new direction for the treatment of lead poisoning.