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双酚A通过下调磷酸化P65核因子-κB信号通路抑制C2C12小鼠成肌细胞的增殖和分化。

Bisphenol-A Abrogates Proliferation and Differentiation of C2C12 Mouse Myoblasts via Downregulation of Phospho-P65 NF-B Signaling Pathway.

作者信息

Tipbunjong Chittipong, Thitiphatphuvanon Thanvarin, Pholpramool Chumpol, Surinlert Piyaporn

机构信息

Department of Anatomy, Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.

Faculty of Medicine, Kasetsart University, Bangkok 10900, Thailand.

出版信息

J Toxicol. 2024 Feb 28;2024:3840950. doi: 10.1155/2024/3840950. eCollection 2024.

Abstract

Previous studies showed that bisphenol-A (BPA), a monomer of polycarbonate plastic, is leached out and contaminated in foods and beverages. This study aimed to investigate the effects of BPA on the myogenesis of adult muscle stem cells. C2C12 myoblasts were treated with BPA in both proliferation and differentiation conditions. Cytotoxicity, cell proliferation and differentiation, antioxidant activity, apoptosis, myogenic regulatory factors (MRFs) gene expression, and mechanism of BPA on myogenesis were examined. C2C12 myoblasts exposed to 25-50 M BPA showed abnormal morphology, expressing numerous and long cytoplasmic extensions. Cell proliferation was inhibited and was accumulated in subG1 and S phases of the cell cycle, subsequently leading to apoptosis confirmed by nuclear condensation and the expression of apoptosis markers, cleaved caspase-9 and caspase-3. In addition, the activity of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase was significantly decreased. Meanwhile, BPA suppressed myoblast differentiation by decreasing the number and size of multinucleated myotubes via the modulation of MRF gene expression. Moreover, BPA significantly inhibited the phosphorylation of P65 NF-B in both proliferation and differentiation conditions. Altogether, the results revealed the adverse effects of BPA on myogenesis leading to abnormal growth and development via the inhibition of phospho-P65 NF-B.

摘要

先前的研究表明,聚碳酸酯塑料的单体双酚A(BPA)会从食品和饮料中渗出并造成污染。本研究旨在调查BPA对成年肌肉干细胞成肌作用的影响。在增殖和分化条件下,用BPA处理C2C12成肌细胞。检测细胞毒性、细胞增殖与分化、抗氧化活性、细胞凋亡、成肌调节因子(MRFs)基因表达以及BPA对成肌作用的机制。暴露于25-50μM BPA的C2C12成肌细胞表现出形态异常,出现大量且长的细胞质延伸。细胞增殖受到抑制,并在细胞周期的G1期和S期积累,随后通过核浓缩以及凋亡标志物(裂解的caspase-9和caspase-3)的表达证实细胞发生凋亡。此外,抗氧化酶过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性显著降低。同时,BPA通过调节MRF基因表达,减少多核肌管的数量和大小,从而抑制成肌细胞分化。此外,在增殖和分化条件下,BPA均显著抑制P65 NF-κB的磷酸化。总之,结果揭示了BPA通过抑制磷酸化P65 NF-κB对成肌作用产生不利影响,导致异常生长和发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca1a/10917485/43b9e9fa8312/JT2024-3840950.001.jpg

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