Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression
© 2024 The Author(s)..
Cigarette smoking (CS) causes skeletal muscle dysfunction, leading to sarcopenia and worse prognosis of patients with diverse systemic diseases. Here, we found that CS exposure prevented C2C12 myoblasts proliferation in a dose-dependent manner. Immunoblotting assays verified that CS exposure promoted the expression of cell cycle suppressor protein p21. Furthermore, CS exposure significantly inhibited replication-dependent (RD) histone transcription and caused S phase arrest in the cell cycle during C2C12 proliferation. Mechanistically, CS deregulated the expression levels of Nuclear Protein Ataxia-Telangiectasia Locus (NPAT/p220). Notably, the proteasome inhibitor MG132 was able to reverse the expression of NPAT in myoblasts, implying that the degradation of CS-mediated NPAT is proteasome-dependent. Overexpression of NPAT also rescued the defective proliferation phenotype induced by CS in C2C12 myoblasts. Taken together, we suggest that CS exposure induces NPAT degradation in C2C12 myoblasts and impairs myogenic proliferation through NPAT associated proteasomal-dependent mechanisms. As an application of the proteasome inhibitor MG132 or overexpression of NPAT could reverse the impaired proliferation of myoblasts induced by CS, the recovery of myoblast proliferation may be potential strategies to treat CS-related skeletal muscle dysfunction.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Current research in toxicology - 6(2024) vom: 14., Seite 100161 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jianfeng [VerfasserIn] |
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| Links: |
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| Themen: |
Cell cycle |
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| Anmerkungen: |
Date Revised 19.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.crtox.2024.100161 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369856910 |
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| 245 | 1 | 0 | |a Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression |
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| 520 | |a © 2024 The Author(s). | ||
| 520 | |a Cigarette smoking (CS) causes skeletal muscle dysfunction, leading to sarcopenia and worse prognosis of patients with diverse systemic diseases. Here, we found that CS exposure prevented C2C12 myoblasts proliferation in a dose-dependent manner. Immunoblotting assays verified that CS exposure promoted the expression of cell cycle suppressor protein p21. Furthermore, CS exposure significantly inhibited replication-dependent (RD) histone transcription and caused S phase arrest in the cell cycle during C2C12 proliferation. Mechanistically, CS deregulated the expression levels of Nuclear Protein Ataxia-Telangiectasia Locus (NPAT/p220). Notably, the proteasome inhibitor MG132 was able to reverse the expression of NPAT in myoblasts, implying that the degradation of CS-mediated NPAT is proteasome-dependent. Overexpression of NPAT also rescued the defective proliferation phenotype induced by CS in C2C12 myoblasts. Taken together, we suggest that CS exposure induces NPAT degradation in C2C12 myoblasts and impairs myogenic proliferation through NPAT associated proteasomal-dependent mechanisms. As an application of the proteasome inhibitor MG132 or overexpression of NPAT could reverse the impaired proliferation of myoblasts induced by CS, the recovery of myoblast proliferation may be potential strategies to treat CS-related skeletal muscle dysfunction | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cell cycle | |
| 650 | 4 | |a Cigarette smoking | |
| 650 | 4 | |a Myoblast proliferation | |
| 650 | 4 | |a NPAT | |
| 650 | 4 | |a Proteasome | |
| 700 | 1 | |a Liu, Jinling |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Jingjing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hongyu |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Luyun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Pei |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Yinan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jianying |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Zhang |e verfasserin |4 aut | |
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