The Effects of Pb on TNF-R1-RIPK1/RIPK3 Signaling Pathway in the Hippocampus of Mice.

Lead (Pb), a dense, soft, blue-gray metal, is widely used in metallurgy, cables, storage batteries, pigments, and other industrial applications. Pb has been shown to cause degenerative changes in the nervous system. Necroptosis, a form of non-apoptotic programmed cell death modality, is closely associated with neurodegenerative diseases. Whether the TNF-R1-RIPK1/RIPK3 pathway is involved in the neurodegeneration induced by Pb has yet to be determined. Here, we explored the role of the TNF-R1-RIPK1/RIPK3 signaling pathway in the Pb-induced necroptosis by using HT-22 cells, primary mouse hippocampal neurons, and C57BL/6 mice models, demonstrating that Pb exposure elevated lead levels in murine whole blood and hippocampal tissue in a dose-response relationship. Protein expression levels of PARP, c-PARP, RIPK1, p-RIPK1, RIPK3, MLKL, and p-MLKL in the hippocampal tissues were elevated, while the protein expression of caspase-8 was decreased. Furthermore, Pb exposure reduced the survival rates in HT-22 cells and primary mouse hippocampal neurons, while increasing the protein expressions of RIPK1 and p-MLKL. Collectively, these novel findings suggest that the TNF-R1/RIPK1/RIPK3 signaling pathway is associated with Pb-induced neurotoxicity in hippocampal neurons in mice. © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Huishuai Li, Zhenning Li, Chun Yang, Ruokun Wei, Peiqi Wei, Haiyan Yuan, Michael Aschner, Shiyan Ou, Dongjie Peng, Shaojun Li. The Effects of Pb on TNF-R1-RIPK1/RIPK3 Signaling Pathway in the Hippocampus of Mice. Neurochemical research. 2024 Nov 27;50(1):36

Mesh Tags

Substances

PMID: 39602045

search → result