Effects of ursolic acid on sub-lesional muscle pathology in a contusion model of spinal cord injury
Autor: | Han Gao, Gregory E. Bigford, Andrew J. Darr, John R. Bethea, Valerie Bracchi-Ricard, Mark S. Nash |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
lcsh:Medicine Gene Expression P70-S6 Kinase 1 Pharmacology Protective Agents Muscle hypertrophy 03 medical and health sciences Random Allocation 0302 clinical medicine Atrophy medicine Animals Muscle Strength lcsh:Science Muscle Skeletal Protein kinase B Spinal cord injury PI3K/AKT/mTOR pathway Spinal Cord Injuries Multidisciplinary business.industry lcsh:R Skeletal muscle Organ Size medicine.disease Muscle atrophy Triterpenes Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Motor Skills lcsh:Q Female medicine.symptom business 030217 neurology & neurosurgery |
Zdroj: | PLoS ONE, Vol 13, Iss 8, p e0203042 (2018) |
ISSN: | 1932-6203 |
Popis: | Spinal Cord Injury (SCI) results in severe sub-lesional muscle atrophy and fiber type transformation from slow oxidative to fast glycolytic, both contributing to functional deficits and maladaptive metabolic profiles. Therapeutic countermeasures have had limited success and muscle-related pathology remains a clinical priority. mTOR signaling is known to play a critical role in skeletal muscle growth and metabolism, and signal integration of anabolic and catabolic pathways. Recent studies show that the natural compound ursolic acid (UA) enhances mTOR signaling intermediates, independently inhibiting atrophy and inducing hypertrophy. Here, we examine the effects of UA treatment on sub-lesional muscle mTOR signaling, catabolic genes, and functional deficits following severe SCI in mice. We observe that UA treatment significantly attenuates SCI induced decreases in activated forms of mTOR, and signaling intermediates PI3K, AKT, and S6K, and the upregulation of catabolic genes including FOXO1, MAFbx, MURF-1, and PSMD11. In addition, UA treatment improves SCI induced deficits in body and sub-lesional muscle mass, as well as functional outcomes related to muscle function, motor coordination, and strength. These findings provide evidence that UA treatment may be a potential therapeutic strategy to improve muscle-specific pathological consequences of SCI. |
Databáze: | OpenAIRE |
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