A diarylheptanoid derivative mediates glycogen synthase kinase 3β to promote the porcine muscle satellite cell proliferation: Implications for cultured meat production.

Autor: Suriya U; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Srikuea R; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Chokpanuwat T; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Suksen K; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Watcharanapapan W; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Saleepimol P; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Laohasinnarong D; Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, 73170, Thailand., Suksamrarn A; Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, 10240, Thailand., Myint KZ; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Janvilisri T; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Chairoungdua A; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand., Bhukhai K; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. Electronic address: kanit.bhu@mahidol.ac.th.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 03; Vol. 736, pp. 150850. Date of Electronic Publication: 2024 Oct 19.
DOI: 10.1016/j.bbrc.2024.150850
Abstrakt: Skeletal muscle stem cells, or satellite cells, are vital for cultured meat production, driving proliferation and differentiation to form muscle fibers in vitro. However, these abilities are often compromised after long-term in vitro culturing due to a loss of their stemness characteristics. Therefore, effective pharmacological agents that enhance satellite cell proliferation and maintain stemness ability are needed for optimal cell growth for cultured meat production. In this study, the effects of the identified glycogen synthase kinase 3β (GSK3β) inhibitors, ASPP 049, a diarylheptanoid isolated from Curcuma comosa rhizomes, and CHIR 99021 on porcine muscle satellite cell (PMSC) proliferation and Wnt/β-catenin signaling pathway were investigated. We found that both compounds enhanced cell viability and proliferation while preserving the stemness marker, as evidenced by increased expression of the skeletal muscle stem cell marker, Pax7 protein. Molecular dynamics simulations showed that ASPP 049 and CHIR 99021 exhibited differing binding affinities, primarily through hydrophobic interactions, suggesting potential for the design of more potent inhibitors in the future. Despite its weaker binding, ASPP 049 still showed significant effects on the regulation of the Wnt/β-catenin signaling pathway via increased phosphorylation of GSK3β at Ser9 and decreased the phosphorylation of β-catenin at Ser33, Ser37, and Thr41, thereby subsequently activating Wnt transcriptional activity. This study highlights the potential of ASPP 049 and CHIR 99021 to enhance PMSC proliferation and maintain stemness ability, offering a promising avenue for improving cultured meat production.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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