Versatile function of AMPK signaling in osteosarcoma: An old player with new emerging carcinogenic functions

Hashemi, Mehrdad; Razzazan, Mehrnaz; Bagheri, Maryam; Asadi, Saba; Jamali, Behdokht; Khalafi, Maryam; Azimi, Abolfazl; Rad, Sepideh; Behroozaghdam, Mitra; Nabavi, Noushin; Rashidi, Mohsen; Dehkhoda, Farshid; Taheriazam, Afshin; Entezari, Maliheh

doi:10.1016/j.prp.2023.154849

Pathology - Research and Practice

2023

DOI: 10.1016/j.prp.2023.154849

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Versatile function of AMPK signaling in osteosarcoma: An old player with new emerging carcinogenic functions

Mehrdad Hashemi,

Mehrnaz Razzazan,

Maryam Bagheri

et al.

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Cited by 3 publications

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

Chen,

Xie,

Liu

et al. 2024

J Sci Food Agric

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BACKGROUNDMaduramicin 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.RESULTSFirst, 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.CONCLUSIONOur findings showed that MA impairs autophagic flux through activating the AMPK‐induced eIF2α‐ATF4 pathway in skeletal muscle. © 2024 Society of Chemical Industry.

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

Chen,

Xie,

Liu

et al. 2024

J Sci Food Agric

View full text Add to dashboard Cite

show abstract

The functions and clinical implications of hsa_circ_0032462-miR-488-3p-SLC7A1 axis in human osteosarcoma

Wang,

Gao,

Yang

et al. 2025

Bone

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Development of novel paullone-based PROTACs as anticancer agents

Manda,

Chatakonda,

Ugale

et al. 2025

Journal of Molecular Structure

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Versatile function of AMPK signaling in osteosarcoma: An old player with new emerging carcinogenic functions

Cited by 3 publications

References 186 publications

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

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

The functions and clinical implications of hsa_circ_0032462-miR-488-3p-SLC7A1 axis in human osteosarcoma

Development of novel paullone-based PROTACs as anticancer agents

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