Maduramicin ammonium impairs autophagic flux through activating AMPK-mediated eIF2α-ATF4 endoplasmic reticulum stress pathway in skeletal muscle.

Autor: Chen X; Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, People's Republic of China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People's Republic of China.; Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou, People's Republic of China., Xie X; Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, People's Republic of China., Liu C; Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, People's Republic of China., Chen L; Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, People's Republic of China., Zhang M; Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, People's Republic of China., Zhang Y; Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Yangzhou University, Yangzhou, People's Republic of China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, People's Republic of China.; Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou, People's Republic of China.
Jazyk: angličtina
Zdroj: Journal of the science of food and agriculture [J Sci Food Agric] 2024 Dec 11. Date of Electronic Publication: 2024 Dec 11.
DOI: 10.1002/jsfa.14071
Abstrakt: Background: Maduramicin ammonium (MA), a widely used coccidiostat, has been reported to cause skeletal muscle degeneration in animals and even humans. In this study, we explore the underlying mechanism of its toxicity in skeletal muscle.
Results: First, we observed that MA impaired autophagic flux which was evidenced by increased protein level of LC3-II and p62 in skeletal myoblast C2C12 and L6 cell lines and rectus femoris muscle tissues of rats and broilers. Then, we found that MA induced eIF2α phosphorylation and ATF4 expression in the cells and tissues. Co-treatment with ISRIB attenuated MA-induced LC3-II and p62 in C2C12 and L6 cells, suggesting that MA-induced eIF2α-ATF4 pathway contributed to impairment of autophagic flux in the cells. Lastly, we showed that MA activated AMPK signaling in skeletal muscle, since the phosphorylation of AMPK was increased by MA treatment in skeletal myoblast cell lines and muscle tissues. Furthermore, in AMPK downregulated C2C12 cells, MA-induced LC3-II, ATF4 and phosphorylation of eIF2α was reversed, supporting that AMPK was involved in the regulation of the eIF2α-ATF4 pathway and autophagic flux during MA exposure.
Conclusion: Our findings showed that MA impairs autophagic flux through activating the AMPK-induced eIF2α-ATF4 pathway in skeletal muscle. © 2024 Society of Chemical Industry.
(© 2024 Society of Chemical Industry.)
Databáze: MEDLINE
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