Notch Inhibition via GSI Treatment Elevates Protein Synthesis in C2C12 Myotubes

التفاصيل البيبلوغرافية
العنوان: Notch Inhibition via GSI Treatment Elevates Protein Synthesis in C2C12 Myotubes
المؤلفون: Susan T. Arthur, Joshua R. Huot, Joseph S. Marino, Michael J. Turner
المصدر: Biology, Vol 9, Iss 115, p 115 (2020)
Biology
Volume 9
Issue 6
بيانات النشر: MDPI AG, 2020.
سنة النشر: 2020
مصطلحات موضوعية: congenital, hereditary, and neonatal diseases and abnormalities, protein synthesis, Notch signaling pathway, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Muscle hypertrophy, GSI, medicine, PTEN, skin and connective tissue diseases, Protein kinase B, lcsh:QH301-705.5, PI3K/AKT/mTOR pathway, General Immunology and Microbiology, Myogenesis, Skeletal muscle, nutritional and metabolic diseases, Cell biology, medicine.anatomical_structure, lcsh:Biology (General), biology.protein, General Agricultural and Biological Sciences, hypertrophy, C2C12, notch
الوصف: The role of Notch signaling is widely studied in skeletal muscle regeneration but little is known about its influences on muscle protein synthesis (MPS). The purpose of this study was to investigate whether Notch signaling is involved in the regulation of MPS. C2C12 cells were treated with a &gamma
secretase inhibitor (GSI), to determine the effect of reduced Notch signaling on MPS and anabolic signaling markers. GSI treatment increased myotube hypertrophy by increasing myonuclear accretion (nuclei/myotube: p = 0.01) and myonuclear domain (myotube area per fusing nuclei: p <
0.001) in differentiating C2C12 cells. GSI treatment also elevated myotube hypertrophy in differentiated C2C12s (area/myotube
p = 0.01). In concert, GSI treatment augmented pmTOR Ser2448 (p = 0.01) and protein synthesis (using SUnSET method) in myotubes (p <
0.001). Examining protein expression upstream of mTOR revealed reductions in PTEN (p = 0.04), with subsequent elevations in pAKT Thr308 (p <
0.001) and pAKT Ser473 (p = 0.05). These findings reveal that GSI treatment elevates myotube hypertrophy through both augmentation of fusion and MPS. This study sheds light on the potential multifaceted roles of Notch within skeletal muscle. Furthermore, we have demonstrated that Notch may modulate the PTEN/AKT/mTOR pathway.
وصف الملف: application/pdf
اللغة: English
تدمد: 2079-7737
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47e697aece3cfd43e86c462160664ccaTest
https://www.mdpi.com/2079-7737/9/6/115Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....47e697aece3cfd43e86c462160664cca
قاعدة البيانات: OpenAIRE