Long-term PGC1β overexpression leads to apoptosis, autophagy and muscle wasting
| العنوان: | Long-term PGC1β overexpression leads to apoptosis, autophagy and muscle wasting |
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| المؤلفون: | Vikas Yadav, Min Sup Song, Qingchun Tong, Eun Ran Kim, Vihang A. Narkar, George G. Rodney, Pierre Marie Badin, Sabina Lorca, Megha Sheth, Neah Likhite, Danesh H. Sopariwala, Isabelle K. Vila |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-16 (2017) Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Genetically modified mouse, medicine.medical_specialty, lcsh:Medicine, Apoptosis, Mice, Transgenic, Biology, Article, Mice, 03 medical and health sciences, Internal medicine, Autophagy, medicine, Animals, E2F1, Nuclear protein, Muscle, Skeletal, lcsh:Science, Myopathy, Insulin-like growth factor 1 receptor, Multidisciplinary, 030102 biochemistry & molecular biology, lcsh:R, Ubiquitination, Nuclear Proteins, Skeletal muscle, Organ Size, Muscular Atrophy, Oxidative Stress, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Proteolysis, lcsh:Q, medicine.symptom, ITGA7, Transcription Factors |
| الوصف: | Skeletal muscle wasting is prevalent in many chronic diseases, necessitating inquiries into molecular regulation of muscle mass. Nuclear receptor co-activator peroxisome proliferator-activated receptor co-activator 1 alpha (PGC1α) and its splice variant PGC1α4 increase skeletal muscle mass. However, the effect of the other PGC1 sub-type, PGC1β, on muscle size is unclear. In transgenic mice selectively over-expressing PGC1β in the skeletal muscle, we have found that PGC1β progressively decreases skeletal muscle mass predominantly associated with loss of type 2b fast-twitch myofibers. Paradoxically, PGC1β represses the ubiquitin-proteolysis degradation pathway genes resulting in ubiquitinated protein accumulation in muscle. However, PGC1β overexpression triggers up-regulation of apoptosis and autophagy genes, resulting in robust activation of these cell degenerative processes, and a concomitant increase in muscle protein oxidation. Concurrently, PGC1β up-regulates apoptosis and/or autophagy transcriptional factors such as E2f1, Atf3, Stat1, and Stat3, which may be facilitating myopathy. Therefore, PGC1β activation negatively affects muscle mass over time, particularly fast-twitch muscles, which should be taken into consideration along with its known aerobic effects in the skeletal muscle. |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::505b6a8ed932cbed50b41469fdd25aa1 https://doi.org/10.1038/s41598-017-10238-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....505b6a8ed932cbed50b41469fdd25aa1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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