JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
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2025
·Vol. 39
·期 9
·e70449
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IF 2.8
Dai Lizhi,Yu Tong,Wang Jingxuan,Li Youchong,Cao Zheyuan,Xiao Jianhua
2-ethylhexyl diphenyl phosphate (EHDPHP), a ubiquitous organic phosphorus flame retardant, is extensively employed in food packaging, flame retardancy applications, and other industrial processes as a crucial chemical. However, recent discoveries have underscored its diverse toxic effects, posing a severe potential threat to biological health. Skeletal muscle, vital for locomotion, relies heavily on proper differentiation during development and maintenance for strength and functionality. This study investigated the impact of EHDPHP on skeletal muscle differentiation by culturing C2C12 cells with varying concentrations of EHDPHP during induction of differentiation, as well as constructing a mouse muscle injury repair model through oral administration of 30 μg/kg EHDPHP for 7 weeks. Exposure to EHDPHP was found to impede skeletal muscle differentiation in mice. Utilizing techniques such as western blot analysis, RNA-seq, and qRT-PCR, our preliminary analysis revealed that low concentrations of EHDPHP inhibited the expression of ACTC1, subsequently suppressing MyoG and MYH2 expression levels, thereby hindering C2C12 myoblast differentiation. Furthermore, EHDPHP exposure disrupted the repair process of muscle injury in mice and compromised the integrity of the repaired tissue. In conclusion, these findings elucidate the detrimental effects of EHDPHP exposure on muscle differentiation, uncovering its muscle toxicity.
研究领域:
毒理学
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分子生物学
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细胞生物学
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药理学
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环境科学
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PubMed
高影响因子
Cell Death & Disease
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2021
·Vol. 12
·期 12
·1-13
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IF 8.469
Tan Yanjie,Jin Yi,Zhao Pengxiang,Wu Jian,Ren Zhuqing
Lipid droplet (LD), a multi-functional organelle, is found in most eukaryotic cells. LDs participate in the regulation of many cellular processes including proliferation, stress, and apoptosis. Previous studies showed the athlete’s paradox that trained athletes accumulate LDs in their skeletal muscle. However, the impact of LDs on skeletal muscle and myogenesis is not clear. We discovered that C2C12 myoblast cells containing more LDs formed more multinucleated muscle fibers. We also discovered that LDs promoted cell migration and fusion by promoting actin-filaments remodeling. Mechanistically, two LD-proteins, Acyl-CoA synthetase long chain family member 3 (ACSL3) and lysophosphatidylcholine acyltransferase 1 (LPCAT1), medicated the recruitment of actinin proteins which contributed to actin-filaments formation on the surface of LDs. During remodeling, the actinin proteins on LDs surface translocated to actin-filaments via ARF1/COPI vesicles. Our study demonstrate LDs contribute to cell differentiation, which lead to new insight into the LD function.
研究领域:
细胞生物学
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分子生物学
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肌肉生理学
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PubMed
高影响因子
PLoS One
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2018
·Vol. 13
·期 5
·e0197934
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IF 2.766
Xi Chen,Long-Yun Li,Jin-Lan Jiang,Kai Li,Zhen-Bo Su,Fu-Qiang Zhang,Wen-Jing Zhang,Guo-Qing Zhao
In this study, we investigated the relationship between propofol and autophagy and examined whether this relationship depends on ER stress, production of ROS (reactive oxygen species), and disruption of calcium (Ca 2+ ) homeostasis. To this end, we measured C2C12 cell apoptosis in vitro , along with Ca 2+ levels; ROS production; and expression of proteins and genes associated with autophagy, Ca 2+ homeostasis, and ER stress, including LC3 (microtubule-associate protein 1 light chain 3), p62, AMPK (adenosine 5’-monophosphate (AMP)-activated protein kinase), phosphorylated AMPK, mTOR (the mammalian target of rapamycin), phosphorylated mTOR, CHOP (C/BEP homologous protein), and Grp78/Bip (78 kDa glucose-regulated protein). We found that propofol treatment induced autophagy, ER stress, and Ca 2+ release. The ratio of phosphorylated AMPK to AMPK increased, whereas the ratio of phosphorylated mTOR to mTOR decreased. Collectively, the data suggested that propofol induced autophagy in vitro through ER stress, resulting in elevated ROS and Ca 2+ . Additionally, co-administration of an ER stress inhibitor blunted the effect of propofol.
研究领域:
药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
Molecular Therapy-Nucleic Acids
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2020
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IF 7.032
Yihao Liu,Jie Wang,Xiaomin Zhou,Haigang Cao,Xiaoyu Zhang,Kuilong Huang,Xiao Li,Gongshe Yang,Xin’e Shi
Skeletal muscle is an important metabolic organ of the body, and impaired skeletal muscle differentiation can result in a wide range of metabolic diseases. It has been shown that microRNAs (miRNAs) play an important role in skeletal muscle differentiation. The aim of this study was to investigate the role of mmu-miR-324-5p in the differentiation of C2C12 myoblasts and lipid droplet deposition in myotubes for future targeted therapies. We found that mmu-miR-324-5p was highly expressed in mouse skeletal muscle. Overexpression of miR-324-5p significantly inhibited C2C12 myoblast differentiation while promoting oleate-induced lipid accumulation and β-oxidation in C2C12 myoblasts. Conversely, inhibition of mmu-miR-324-5p promoted C2C12 myoblast differentiation and inhibited lipid deposition in myotubes. Mechanistically, mmu-miR-324-5p negatively regulated the expression of long non-coding Dum (lncDum) and peptidase M20 domain containing 1 (Pm20d1) in C2C12 myoblasts. Reduced lncDum expression was associated with a significant decrease in the expression of myogenesis-related genes. Knockdown of mmu-miR-324-5p increased the levels of lncDum and myogenesis-related gene expression. Following oleate-induced lipid deposition in C2C12 myoblasts, overexpression of mmu-miR-324-5p decreased the expression of Pm20d1 while increasing the expression of mitochondrial β-oxidation and long-chain fatty acid synthesis-related genes. In conclusion, we provide evidence that miR-324-5p inhibits C2C12 myoblast differentiation and promotes intramuscular lipid deposition by targeting lncDum and Pm20d1, respectively.
研究领域:
分子生物学
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细胞生物学
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肌肉生理学
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代谢
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PubMed
高影响因子
ACS Applied Materials & Interfaces
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2019
·
IF 8.456
Xiaoxiao Chen,Wenqiang Du,Ze Cai,Shengyun Ji,Monika Dwivedi,Jianfeng Chen,Gang Zhao,Jiaru Chu
Fiber-shaped cellular constructs have attracted increasing attention in the regeneration of blood vessels, nerve networks, and skeletal myofibers. Nevertheless, the generation of functional fiber-shaped cellular constructs suffers from limited appropriate microfiber-based fabrication approaches and the maintenance of regenerated tissue functions. Herein, we demonstrate a silicone-tube-based coagulant bath free method to fabricate tens of centimeters long cell-laden microfibers using single UV exposure without pretreatment of nozzles or microchannels. By modulating the exposure time, the gelatin methacrylate microfibers with tissue-like microstructures and mechanical properties are obtained. Then, a culture system integrated with a pillar well-array based stretching device is used to apply uniaxial stretching with various strain ratios in situ to cell-laden microfibers in a 60 mm petri dish. Cells with improved spreading, elongation, and alignment are obtained under uniaxial stretching. Moreover, the promotional effects of uniaxial stretching on the differentiation of C2C12 myoblasts, the formation, and contractility of myofibers become more pronounced with increasing strain ratio and achieve saturation level as strain ratio up to ∼35%.
研究领域:
组织工程
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生物医学工程
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细胞生物学
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材料科学
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PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2018
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IF 4.235
Binbin Sun,Zeyu Zhong,Fan Wang,Jiong Xu,Feng Xu,Weimin Kong,Zhaoli Ling,Nan Shu,Ying Li,Tong Wu,Mian Zhang,Liang Zhu,Xiaodong Liu,Li Liu
Skeletal muscle accounts for approximately 75% of glucose disposal in body and statins impair glucose metabolism. We aimed to investigate the effect of atorvastatin on glucose metabolism in C2C12 cells. Glucose metabolism and expression of glucose transporter 4 (GLUT4) and hexokinase II (HXKII) were measured following incubation with atorvastatin or pravastatin . Roles of cholesterol in atorvastatin-induced glucose metabolism impairment were investigated via adding cholesterol or mevalonic acid and confirmed by cholesterol depletion with methyl-β-cyclodextrin. Hypercholesterolemia mice induced by high fat diet (HFD) feeding, orally received atorvastatin (6 and 12 mg/kg) or pravastatin (12 mg/kg) for 22 days. Results showed that atorvastatin not pravastatin concentration-dependently impaired glucose consumption, glucose uptake and GLUT4 membrane translocation in C2C12 cells without affecting expression of HXKII or total GLUT4 protein. The atorvastatin-induced alterations were reversed by cholesterol or mevalonic acid. Cholesterol depletion exerted similar impact to atorvastatin, which could be alleviated by cholesterol supplement. Glucose consumption or GLUT4 translocation was positively associated with cellular cholesterol levels. In HFD mice, atorvastatin not pravastatin significantly increased blood glucose levels following glucose or insulin dose and decreased expression of membrane not total GLUT4 protein in muscle. Glucose exposure following glucose or insulin dose was negatively correlated to muscular free cholesterol concentration. Expression of membrane GLUT4 protein was positively related to free cholesterol in muscle. In conclusion, atorvastatin impaired glucose utilization in muscle cells partly via inhibiting GLUT4 membrane translocation due to inhibition of cholesterol synthesis by atorvastatin, at least, partly contributing to glucose intolerance in HFD mice.
研究领域:
药理学
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细胞生物学
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代谢
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内分泌学
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PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Ning Xu,Guanzheng Cui,Shengyin Zhao,Yu Li,Qian Liu,Xuchang Liu,Chuanliang Zhao,Rongjie Feng,Mingjie Kuang,Shijie Han
Introduction Osteoporosis is a common bone disease in which the bone loses density and strength and is prone to fracture. Bone marrow mesenchymal stem cells (BMSCs) are important in bone-related diseases. Exosomes, as mediators of cell communication, have potential in cell processes. Previous studies have focused on muscle factors’ regulation of bone remodeling, but research on exosomes is lacking.Methods In order to confirm the therapeutic effect of mechanically stimulated myocytes (C2C12) derived exosomes (Exosome-MS) on the Glucocorticoid-induced osteoporosis(GIOP) compared with unmechanically stimulated myocytes (C2C12) derived exosomes (Exosomes), we established a dexamethasone-induced osteoporosis model in vivo and in vitro. Cell viability and proliferation were assessed using CCK8 and EDU assays. Osteogenic potential was evaluated through Western blotting, real-time PCR, alkaline phosphatase activity assay, and alizarin red staining. Differential expression of miRNAs was determined by high-throughput sequencing. The regulatory mechanism of miR-92a-3p on cell proliferation and osteogenic differentiation via the PTEN/AKT pathway was investigated using real-time PCR, luciferase reporter gene assay, Western blotting, and immunofluorescence. The therapeutic effects of exosomes were evaluated in vivo using microCT, HE staining, Masson staining, and immunohistochemistry.Results In this study, we found that exosomes derived from mechanical stress had a positive impact on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). Importantly, we demonstrated that miR-92a-3p mimics could reverse dexamethasone-induced osteoporosis in vitro and in vivo, indicating that mechanical stress-induced mouse myoblast-derived exosomes could promote osteogenesis and prevent the occurrence and progression of osteoporosis in mice through miR-92a-3p/PTEN/AKT signaling pathway.Conclusion Exosomes derived from mechanical stress-induced myoblasts can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through miR-92a-3p/PTEN/AKT signaling pathway, and can have a therapeutic effect on glucocorticoid-induced osteoporosis in mice in vivo.
研究领域:
骨科
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细胞生物学
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分子生物学
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再生医学
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PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Yaozhu Fan,Xuefeng Wang,Yiyan Li,Lingfei Li,Yang Tian
The hypoglycemic peptide MoHpP-2 from Moringa oleifera seeds exhibits excellent α-glucosidase inhibitory activity, but its amelioration in insulin resistant (IR) cells and type 2 diabetes mellitus (T2DM) mice is still unclear. Therefore, the present study aimed to investigate the hypoglycemic effect of MoHpP-2 on C2C12/IR cells, and gut microbiota and metabolite changes of T2DM mice using 16S rRNA high-throughput sequencing and metabolomics. MoHpP-2 within the concentration range could effectively enhance the glucose consumption levels and antioxidant capacity in C2C12/IR cells. MoHpP-2 intervention improves the blood sugar levels, liver function, and organ indices, reverses oxidative damage, and enhances the antioxidant capacity of T2DM mice. Furthermore, it increases the diversity of cecum microorganisms, decreases the ratio of Firmicutes to Bacteroides and some pathogenic bacteria , and reshapes the gut microbial composition of T2DM mice. Moreover, the metabolomic analysis results showed that MoHpP-2 intervention might promote unsaturated fatty acid biosynthesis, inhibit bile acid formation, and regulate linoleic acid metabolism and amino acid metabolism related to oxidative stress, thereby improving insulin resistance and sensitivity in T2DM mice. Overall, the experimental results provide insights into the hypoglycemic effect of MoHpP-2 in vitro and in vivo and its application in hypoglycemic functional food products.
研究领域:
药理学
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营养学
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微生物学
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代谢组学
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高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
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IF 4.259
Chen Xubo,Zhao Xueyan,Lan Fazhang,Zhou Tao,Cai Hua,Sun Haiying,Kong Weijia,Kong Wen
Studies have reported attenuation of insulin resistance (IR) by improving phosphorylation of the insulin signalling pathway. However, the upstream molecular signalling pathway is still elusive. In this study, Western blot was used to evaluate the phosphorylation level of the insulin signalling pathway and the AMPK pathway. 2-NBDG was used to evaluate glucose uptake. Ca 2+ imaging was used to assess change of intracellular Ca 2+ concentration. We found that NaHS enhanced the intracellular Ca 2+ concentration and glucose uptake and activated the insulin signalling cascade in a palmitic acid (PA)-induced IR model in C2C12 cells. Furthermore, activation of the IRS1/PI3K/AKT pathway and glucose uptake were decreased when AMPK or CaMKKβ was inhibited. Our study also showed that the mitochondrial electron transport chain, ATP production, and intramitochondrial cAMP declined in the IR model but that this effect was reversed by NaHS, an effect that may be mediated by the Ca 2+ /CaMKK2/AMPK and PI3K/AKT pathways. Our data indicate that H 2 S improves activation of the insulin signalling cascade and glucose uptake via activation of the Ca 2+ /CaMKK2/AMPK pathway and mitochondrial metabolism in C2C12 cells. Furthermore, NaHS protects mitochondrial function and maintains normal ATP production by activating the cAMP system and the Ca 2+ /CaMKK2/AMPK and PI3K/ATK pathways.
研究领域:
分子生物学
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细胞代谢
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内分泌学
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糖尿病研究
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DOI
PubMed
高影响因子
Toxics
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2026
·Vol. 14
·期 7
·623
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IF 4.9
Jingyu Zhao,Yingnan An,Jiankai Shi,Libing Ma,Xiaoying He,Ying Liu,Chuncheng Liu
The effects of scandium on skeletal muscle cells remain poorly understood. This study aims to determine whether scandium chloride (ScCl3) affects C2C12 myoblast proliferation, and the cellular responses were assessed using CCK-8, flow cytometry, RNA-seq, and bioinformatic analyses after treatment with 0.01 mM and 1 mM ScCl3. We verified that 1 mM ScCl3significantly promoted cell proliferation by inducing the G1/S phase transition, while the low concentration had no significant effect. However, GO enrichment analysis failed to capture proliferation-related terms among the top 20 ranked terms. To address this, we grouped genes based on their expression patterns and combined transcription factor activity inference with Hallmark pathway enrichment. This strategy identified distinct functional modules responsive to scandium, involving mitosis, myogenesis, and metabolism, with key regulators including Foxo1, Rela, and myogenic transcription factors. Collectively, our findings suggest that scandium may exert regulatory effects on myoblast proliferation and modulate genes involved in differentiation and metabolism by coordinating multiple functional modules.
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Food & Function
·
2026
·Vol. 17
·期 11
·5152-5169
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IF 6.3
Xin Cao,Hongjuan Liu,Miao Yang,Zhixian Chen,Qian Cheng,Jialin Sun,Xudong Wu,Yan Zhang,Liping Hao
Yeast protein (YP) is a sustainable alternative protein, offering a favorable amino acid profile. However, its digestion kinetics and potential as a source of bioactive peptides (BAPs) remain neglected. This study applied the INFOGEST digestion model to compare in vitro digestion kinetics of YP, whey and soy protein. YP exhibited delayed amino acid release and distinct proteomic features. Analysis of the final intestinal chyme of YP identified 312 unique peptides. In silico screening identified several low-molecular-weight peptides (<1000 Da) with high bioactivity potential and favorable pharmacokinetics. Crucially, cell-based assays revealed that two high-abundance peptides, GDWPLPT and PLPPAPAPK, significantly alleviated lipopolysaccharide (LPS)-induced injury in C2C12 myotubes. These peptides reduced reactive oxygen species (ROS) levels and interleukin-6 (IL-6) secretion, while restoring mitochondrial membrane potential and adenosine triphosphate (ATP) synthesis. Overall, this study provides a comprehensive characterization of the digestion kinetics and peptide profiles of YP. Beyond these findings, the cytoprotective potential of the identified peptides was validated in a muscle injury model, thereby proving YP as a promising source of functional food ingredients for future applications.
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PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2026
·
IF 4
Liu Hengxu,Xiong Rui,Zhang Shipeng,Zheng Quanyou,Lai Xiaodan
Fatigue is a widespread health problem, and abnormal autophagy in skeletal muscle cells is a key mechanism driving fatigue progression. The purpose of this study was to evaluate the effect of ginsenoside Rg3 (Rg3) on fatigue in ammonium chloride (NH 4 Cl)-induced C2C12 myoblasts cells and to elucidate its potential molecular mechanism. The potential anti-fatigue mechanism of Rg3 was predicted by network pharmacology and molecular dynamics simulations. C2C12 cells were treated with NH 4 Cl to construct an in vitro fatigue model and then treated with Rg3. CCK-8, live/dead staining, Giemsa staining, autolysosome staining, and Western blot were used to evaluate cell viability, myotube morphology, autophagic flow, and key protein expression. Network pharmacology analysis indicated that the anti-fatigue effect of Rg3 was associated with the PI3K/AKT/mTOR pathway-regulated autophagy. Molecular docking and molecular dynamics simulations confirmed that Rg3 binds strongly to PI3K. Cell experiments showed that Rg3 significantly attenuated cell death, myotube injury and abnormal autophagy in NH 4 Cl-induced C2C12 cells. Moreover, Rg3 effectively activated the PI3K/AKT/mTOR pathway. Our results indicated that the anti-fatigue effect of Rg3 may be associated with the attenuation of autophagy through activation of the PI3K/AKT/mTOR pathway. This provides a potential therapeutic candidate for fatigue intervention.
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高影响因子
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