Effect of the lysosomotropic agent chloroquine on mTORC1 activation and protein synthesis in human skeletal muscle
| العنوان: | Effect of the lysosomotropic agent chloroquine on mTORC1 activation and protein synthesis in human skeletal muscle |
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| المؤلفون: | Melissa M. Markofski, Michael S. Borack, Paul T. Reidy, Christopher S. Fry, Rachel R Deer, Elena Volpi, Kristofer Jennings, Blake B. Rasmussen, Jared M. Dickinson |
| المصدر: | Nutrition & Metabolism, Vol 18, Iss 1, Pp 1-13 (2021) Nutrition & Metabolism |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | RC620-627, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), P70-S6 Kinase 1, mTORC1, Pharmacology, 03 medical and health sciences, 0302 clinical medicine, Chloroquine, Muscle protein turnover, medicine, Myocyte, Amino acid sensing, TX341-641, Kinase activity, Nutritional diseases. Deficiency diseases, 030304 developmental biology, 0303 health sciences, Nutrition and Dietetics, Chemistry, Nutrition. Foods and food supply, Research, Skeletal muscle, medicine.anatomical_structure, mTOR signaling, Phosphorylation, Leucine, biological phenomena, cell phenomena, and immunity, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | Background Previous work in HEK-293 cells demonstrated the importance of amino acid-induced mTORC1 translocation to the lysosomal surface for stimulating mTORC1 kinase activity and protein synthesis. This study tested the conservation of this amino acid sensing mechanism in human skeletal muscle by treating subjects with chloroquine—a lysosomotropic agent that induces in vitro and in vivo lysosome dysfunction. Methods mTORC1 signaling and muscle protein synthesis (MPS) were determined in vivo in a randomized controlled trial of 14 subjects (10 M, 4 F; 26 ± 4 year) that ingested 10 g of essential amino acids (EAA) after receiving 750 mg of chloroquine (CHQ, n = 7) or serving as controls (CON, n = 7; no chloroquine). Additionally, differentiated C2C12 cells were used to assess mTORC1 signaling and myotube protein synthesis (MyPS) in the presence and absence of leucine and the lysosomotropic agent chloroquine. Results mTORC1, S6K1, 4E-BP1 and rpS6 phosphorylation increased in both CON and CHQ 1 h post EAA ingestion (P P = 0.06; CHQ, P P Conclusions Chloroquine did not inhibit amino acid-induced activation of mTORC1 signaling and skeletal MPS in humans as it does in C2C12 muscle cells. Therefore, different in vivo experimental approaches are required for confirming the precise role of the lysosome and amino acid sensing in human skeletal muscle. Trial registration NCT00891696. Registered 29 April 2009. |
| اللغة: | English |
| تدمد: | 1743-7075 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d1b8dbbc9c77bb0c5609871d719205c6 https://doaj.org/article/3a713d11a58f498f85e33400471fcb59 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d1b8dbbc9c77bb0c5609871d719205c6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17437075 |
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