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Promotion of Lead-induced Cytotoxicity in Differentiating Neural Cells and Protective Effects of Selenium
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DOI：10.1007/s12011-026-05285-1.png)
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Abstract
En 中文
Lead (Pb) exposure remains a global health concern, particularly because of its adverse effects on neurodevelopment during fetal development and childhood. Early-life exposure to Pb during neuronal differentiation can impair neurodevelopment, although the underlying molecular mechanisms remain unclear. In this study, we investigated the cellular and molecular mechanisms underlying Pb-induced neurotoxicity during neural differentiation using SH-SY5Y cells. Our results demonstrated that Pb exposure caused severe injury to differentiating neural cells, leading to cell death with membrane disruption. This form of cell death was resistant to inhibitors of major regulated cell death pathways but was markedly suppressed by selenium supplementation with selenite or by the addition of selenoprotein P, a selenium transport protein. Transcriptome and protein expression analyses revealed that Pb induced endoplasmic reticulum (ER) stress responses. However, individual knockdown of selected ER-resident selenoproteins, including SELENOK, SELENOS, and SELENOT, did not abolish the protective effect of selenium, indicating that none of these proteins is individually indispensable for protection under the present experimental conditions. Peroxiredoxin 6 (PRDX6) knockout SH-SY5Y cells, which exhibit reduced selenium metabolic activity, remained responsive to the protective effect of selenium against Pb-induced cytotoxicity. Moreover, the glutathione peroxidase (GPx) mimetic ebselen also alleviated Pb toxicity under these conditions. These findings indicate that selenium protects differentiating neural cells against Pb-induced injury through mechanisms involving peroxide-reducing activity as well as additional selenium-dependent pathways. Collectively, our findings provide new insights into the molecular basis of Pb-induced neurotoxicity and support a protective role for selenium-dependent stress resistance against Pb-induced cellular injury.
Keywords:
Selenoprotein P
Selenium
Lead
Differentiation
Glutathione Peroxidase
Neurotoxicity
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