Puerarin alleviates cadmium-induced mitochondrial mass decrease by inhibiting PINK1-Parkin and Nix-mediated mitophagy in rat cortical neurons

Shuangquan Wen; Li Wang; Tao Wang; Mingchang Xu; Wenhua Zhang; Ruilong Song; Hui Zou; Jianhong Gu; Jianchun Bian; Yan Yuan; Zongping Liu

doi:10.1016/j.ecoenv.2021.113127

Puerarin alleviates cadmium-induced mitochondrial mass decrease by inhibiting PINK1-Parkin and Nix-mediated mitophagy in rat cortical neurons

Ecotoxicol Environ Saf. 2022 Jan 15:230:113127. doi: 10.1016/j.ecoenv.2021.113127. Epub 2021 Dec 31.

Authors

Affiliations

¹ College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
² College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. Electronic address: yuanyan@yzu.edu.cn.
³ College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. Electronic address: liuzongping@yzu.edu.cn.

PMID: 34979308
DOI: 10.1016/j.ecoenv.2021.113127

Abstract

Cadmium (Cd) has well-known central nervous system toxicity, and mitochondria are direct targets of Cd-induced neuronal toxicity. However, how Cd induces mitochondrial mass decrease in terms of its neurotoxic effects remains unknown. Puerarin, an isoflavone extracted from kudzu root, can cross the blood-brain barrier and exert protective effects in nervous system disease. The purpose of the study was to determine the mechanism of Cd-induced mitochondrial mass decrease and the protective role of puerarin in rat cortical neurons. The results indicated that Cd induced mitochondrial mass decrease by activating mitophagy mediated by the PTEN-induced putative kinase protein 1 (PINK1)-E3 ubiquitin ligase (Parkin) and Nip3-like protein X (Nix) pathways in rat cortical neurons. Puerarin improved the Cd-induced decrease in mitochondrial membrane potential (MMP) in vitro, and blocked PINK1-Parkin and Nix-mediated mitophagy, inhibiting Cd-induced mitochondrial mass decrease in rat cortical neurons in vitro and in vivo. In summary, our data clearly indicated that puerarin protects rat cortical neurons against Cd-induced neurotoxicity by ameliorating mitochondrial damage, inhibiting mitophagy-mediated mitochondrial mass decrease. Puerarin appears to have great potential as a neuroprotective agent.

Keywords: Cadmium; Mitochondrial mass; Mitophagy; Neuron; Puerarin.