Reduced sucrose nonfermenting AMPK-related kinase (SNARK) activity aggravates cancer-induced skeletal muscle wasting
Autor: | Tara MacDonald, Laurie J. Goodyear, Sarah J. Lessard, Pasquale Nigro, Prerana Pathak, Michael F. Hirshman, Christiano R. R. Alves |
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Rok vydání: | 2019 |
Předmět: |
AMPK
0301 basic medicine Genetically modified mouse Sucrose Aging medicine.medical_specialty Cachexia Apoptosis Mice Transgenic RM1-950 AMP-Activated Protein Kinases Protein Serine-Threonine Kinases Biology Article Carcinoma Lewis Lung Mice 03 medical and health sciences 0302 clinical medicine Atrophy Internal medicine medicine Animals Muscle Skeletal Wasting Pharmacology Kinase Skeletal muscle Cancer cachexia General Medicine medicine.disease Muscle atrophy Mice Inbred C57BL Muscular Atrophy 030104 developmental biology Endocrinology medicine.anatomical_structure 030220 oncology & carcinogenesis Therapeutics. Pharmacology medicine.symptom |
Zdroj: | Biomedicine & Pharmacotherapy, Vol 117, Iss, Pp-(2019) Biomed Pharmacother |
ISSN: | 0753-3322 |
Popis: | Sucrose nonfermenting AMPK-related kinase (SNARK) is a member of the AMPK family of kinases and has been implicated in the regulation of critical metabolic processes. Recent findings demonstrate that SNARK has an important role in the maintenance of muscle mass with age. Loss of skeletal muscle mass (cachexia) is a key problem for cancer patients. Thus, based on our previous findings with aging, we hypothesized that SNARK would play a role in regulating muscle mass under conditions of cancer cachexia. To test this hypothesis, Lewis Lung Carcinoma tumor cells or vehicle were injected subcutaneously in the right flank of wild type mice, muscle-specific transgenic mice expressing inactive SNARK mutant (SDN) or muscle-specific transgenic mice overexpressing wild-type SNARK (SWT). All tumor-bearing mice presented muscle wasting compared to vehicle-injected mice. However, SDN tumor-bearing mice had more pronounced atrophy compared to wild-type and SWT tumor-bearing mice. Histological analysis confirmed muscle atrophy in tumor-bearing mice, and SDN tumor-bearing mice exhibited a significantly smaller skeletal muscle cross-sectional area than wild-type and SWT tumor-bearing mice. Moreover, SDN tumor-bearing mice had increased skeletal muscle BAX protein expression, a marker of apoptosis, compared to other groups.Thus, lack of SNARK in skeletal muscle aggravates cancer-induced skeletal muscle wasting. These findings uncover a role for SNARK in the maintenance of skeletal muscle mass under cachexia conditions. |
Databáze: | OpenAIRE |
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