Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression
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 promote...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X24000148 |
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| author | Jianfeng Wang Jinling Liu Jingjing Shao Hongyu Chen Luyun Cui Pei Zhang Yinan Yao Jianying Zhou Zhang Bao |
| author_facet | Jianfeng Wang Jinling Liu Jingjing Shao Hongyu Chen Luyun Cui Pei Zhang Yinan Yao Jianying Zhou Zhang Bao |
| author_sort | Jianfeng Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-25T01:19:12Z |
| format | Article |
| id | doaj.art-5c8668b0c6b54054a90555f823d4b0ba |
| institution | Directory Open Access Journal |
| issn | 2666-027X |
| language | English |
| last_indexed | 2024-04-25T01:19:12Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj.art-5c8668b0c6b54054a90555f823d4b0ba2024-03-09T09:29:28ZengElsevierCurrent Research in Toxicology2666-027X2024-01-016100161Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progressionJianfeng Wang0Jinling Liu1Jingjing Shao2Hongyu Chen3Luyun Cui4Pei Zhang5Yinan Yao6Jianying Zhou7Zhang Bao8Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDepartment of Pulmonology, the Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310058 ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaSchool of Medicine, Hangzhou City University, Hangzhou 310015, China; Institute of Bioinformatics and James D. Watson Institute of Genome Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Corresponding authors.Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2666027X24000148Cigarette smokingMyoblast proliferationCell cycleNPATProteasome |
| spellingShingle | Jianfeng Wang Jinling Liu Jingjing Shao Hongyu Chen Luyun Cui Pei Zhang Yinan Yao Jianying Zhou Zhang Bao Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression Current Research in Toxicology Cigarette smoking Myoblast proliferation Cell cycle NPAT Proteasome |
| title | Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression |
| title_full | Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression |
| title_fullStr | Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression |
| title_full_unstemmed | Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression |
| title_short | Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression |
| title_sort | cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of npat protein and hindering cell cycle progression |
| topic | Cigarette smoking Myoblast proliferation Cell cycle NPAT Proteasome |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X24000148 |
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