Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin–p53 interaction
Abstract Background Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a stat...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Skeletal Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13395-022-00302-y |
| _version_ | 1818017905928830976 |
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| author | Yaoxian Xiang Zongqi You Xinying Huang Junxi Dai Junpeng Zhang Shuqi Nie Lei Xu Junjian Jiang Jianguang Xu |
| author_facet | Yaoxian Xiang Zongqi You Xinying Huang Junxi Dai Junpeng Zhang Shuqi Nie Lei Xu Junjian Jiang Jianguang Xu |
| author_sort | Yaoxian Xiang |
| collection | DOAJ |
| description | Abstract Background Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a state of cell growth arrest owing to such stimuli as oxidation, can be caused by progerin. However, evidence for whether SIPS-induced progerin accumulation is connected to denervation-induced muscle atrophy is not sufficient. Methods Flow cytometry and a reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) inhibitors were used to assess the effect of oxidation on protein (p53), progerin, and nuclear progerin–p53 interaction in the denervated muscles of models of mice suffering from sciatic injury. Loss-of-function approach with the targeted deletion of p53 was used to assess connection among SIPS, denervated muscle atrophy, and fibrogenesis. Results The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. The abnormal accumulation of progerin in the nuclear membrane as well as the activation of nuclear progerin–p53 interaction triggered premature senescence in the denervated muscle cells of mice. The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis. Conclusion Oxidative stress-triggered premature senescence via nuclear progerin–p53 interaction that promotes denervated skeletal muscular atrophy and fibrogenesis. |
| first_indexed | 2024-04-14T07:32:48Z |
| format | Article |
| id | doaj.art-497819a00ca642e2ba3d3da004b2b917 |
| institution | Directory Open Access Journal |
| issn | 2044-5040 |
| language | English |
| last_indexed | 2024-04-14T07:32:48Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Skeletal Muscle |
| spelling | doaj.art-497819a00ca642e2ba3d3da004b2b9172022-12-22T02:05:47ZengBMCSkeletal Muscle2044-50402022-07-0112111210.1186/s13395-022-00302-yOxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin–p53 interactionYaoxian Xiang0Zongqi You1Xinying Huang2Junxi Dai3Junpeng Zhang4Shuqi Nie5Lei Xu6Junjian Jiang7Jianguang Xu8Department of Hand Surgery, Huashan Hospital, Fudan UniversityDepartment of Hand Surgery, Huashan Hospital, Fudan UniversityDepartment of Hand Surgery, Huashan Hospital, Fudan UniversityDepartment of Hand Surgery, Huashan Hospital, Fudan UniversitySchool of Rehabilitation Science, Shanghai University of Traditional Chinese MedicineShanghai Medical College of Fudan UniversityDepartment of Hand Surgery, Huashan Hospital, Fudan UniversityDepartment of Hand Surgery, Huashan Hospital, Fudan UniversityDepartment of Hand Surgery, Huashan Hospital, Fudan UniversityAbstract Background Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a state of cell growth arrest owing to such stimuli as oxidation, can be caused by progerin. However, evidence for whether SIPS-induced progerin accumulation is connected to denervation-induced muscle atrophy is not sufficient. Methods Flow cytometry and a reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) inhibitors were used to assess the effect of oxidation on protein (p53), progerin, and nuclear progerin–p53 interaction in the denervated muscles of models of mice suffering from sciatic injury. Loss-of-function approach with the targeted deletion of p53 was used to assess connection among SIPS, denervated muscle atrophy, and fibrogenesis. Results The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. The abnormal accumulation of progerin in the nuclear membrane as well as the activation of nuclear progerin–p53 interaction triggered premature senescence in the denervated muscle cells of mice. The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis. Conclusion Oxidative stress-triggered premature senescence via nuclear progerin–p53 interaction that promotes denervated skeletal muscular atrophy and fibrogenesis.https://doi.org/10.1186/s13395-022-00302-yROSNODenervated muscle atrophyProgerinP53 |
| spellingShingle | Yaoxian Xiang Zongqi You Xinying Huang Junxi Dai Junpeng Zhang Shuqi Nie Lei Xu Junjian Jiang Jianguang Xu Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin–p53 interaction Skeletal Muscle ROS NO Denervated muscle atrophy Progerin P53 |
| title | Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin–p53 interaction |
| title_full | Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin–p53 interaction |
| title_fullStr | Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin–p53 interaction |
| title_full_unstemmed | Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin–p53 interaction |
| title_short | Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin–p53 interaction |
| title_sort | oxidative stress induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin p53 interaction |
| topic | ROS NO Denervated muscle atrophy Progerin P53 |
| url | https://doi.org/10.1186/s13395-022-00302-y |
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