title: Short-term ursolic acid promotes skeletal muscle rejuvenation through enhancing of SIRT1 expression and satellite cells proliferation.
abstract: Ursolic acid (UA) is a triterpenoid compound, which exerts its influences on the skeletal muscles. However, the mechanisms underlying these effects are still unclear. In this study, muscle satellite cells were isolated and purified by high-throughput pre-plating method (∼>60%) from 10 days old mice skeletal muscles. Evaluation of paired-box 7 (Pax7) expressions then confirmed the purification. Treatment of the cells with UA showed that UA up-regulated SIRT1 (∼35 folds) and overexpressed PGC-1α (∼175 folds) gene significantly. Moreover, the number of muscle satellite cells, which accompanied by initiation of neomyogenesis in the animal skeletal muscles, was increased (∼3.4 times). We also evaluated UA-mediated changes in the cellular energy status in the skeletal muscles. The results revealed that in the UA-treated mice, ATP and ADP contents in the various skeletal muscle tissue types, including: Gastrocnemius (Gas), Tibialis Anterior (Tib) and Gluteus Maximus (Glu) have been significantly decreased (P≤0.001); 2.2, 3.2, 2 times for ATP, and 9.6, 35.7, 11.6 times for ADP, respectively; however to compensate this process mitochondrial biogenesis occurred (12.33%±1.5 times). Furthermore, a rise in ATP/ADP ratio was observed 2.5, 4.5, 2.05 times for Gas, Tib and Glu muscles, respectively (P≤0.001). Alternatively, UA enhanced the expression of myoglobin (∼2 folds) in concert with remodeling of glycolytic muscle fibers to mainly fast IIA (∼30%) and slow-twitch (∼4%) types as well. Finally, our study indicated that UA indirectly mimicked beneficial effects of short-term calorie restriction and exercise (fast-oxidative) by directing the skeletal muscle composition toward oxidative metabolism.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Nuredin
authors.initials: N
authors.lastname: Bakhtiari
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: saman_h@modares.ac.ir.
authors.forename: Saman
authors.initials: S
authors.lastname: Hosseinkhani
authors.affiliation: Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Department of Biology, Faculty of Basic Sciences, Shahrekord University, Iran.
authors.forename: Roohullah
authors.initials: R
authors.lastname: Hemmati
authors.affiliation: Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Noori-Zadeh
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.affiliation: Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran.
authors.forename: Amin
authors.initials: A
authors.lastname: Tashakor
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D004734:Energy Metabolism / Q000187:drug effects; D005215:Fasting / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009211:Myoglobin / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D012060:Rejuvenation / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D056564:Sirtuin 1 / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D001786:Blood Glucose; D009211:Myoglobin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D056564:Sirtuin 1; D014315:Triterpenes; D000097245:Ursolic Acid; C485290:Ppargc1a protein, mouse
keywords: Muscle satellite cells; PGC-1α; SIRT1; Ursolic acid