title: Tetramethylpyrazine ameliorated disuse-induced gastrocnemius muscle atrophy in hindlimb unloading rats through suppression of Ca2+/ROS-mediated apoptosis.
abstract: The purpose of this study was to examine the possible mechanism underlying the protective effect of tetramethylpyrazine (TMP) against disuse-induced muscle atrophy. Sprague-Dawley rats were randomly assigned to receive 14 days of hindlimb unloading (HLU, a model of disuse atrophy) or cage controls. The rats were given TMP (60 mg/kg body mass) or vehicle (water) by gavage. Compared with vehicle treatment, TMP significantly attenuated the loss of gastrocnemius muscle mass (-33.56%, P < 0.01), the decrease of cross-sectional area of slow fiber (-10.99%, P < 0.05) and fast fiber (-15.78%, P < 0.01) during HLU. Although TMP failed to further improve recovery of muscle function or fatigability compared with vehicle treatment, it can suppress the higher level of lactate (-22.71%, P < 0.01) induced by HLU. Besides, TMP could effectually reduce the increased protein expression of muscle RING-finger protein 1 induced by HLU (-14.52%, P < 0.01). Furthermore, TMP can ameliorate the calcium overload (-54.39%, P < 0.05), the increase of malondialdehyde content (-19.82%, P < 0.05), the decrease of superoxide dismutase activity (21.34%, P < 0.05), and myonuclear apoptosis (-78.22%, P < 0.01) induced by HLU. Moreover, TMP significantly reduced HLU-induced increase of Bax to B-cell lymphoma 2 (-36.36%, P < 0.01) and cytochrome c release (-36.16%, P < 0.05). In conclusion, TMP attenuated HLU-induced gastrocnemius muscle atrophy through suppression of Ca2+/reactive oxygen species increase and consequent proteolysis and apoptosis. Therefore, TMP might exhibit therapeutic effect against oxidative stress, cytosolic calcium overload, and mitochondrial damage in disuse-induced muscle atrophy.
authors.affiliation: a Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an 710069, China.|b Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China.
authors.forename: Nai-Fei
authors.initials: NF
authors.lastname: Hu
authors.affiliation: a Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an 710069, China.|b Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chang
authors.affiliation: c Shaanxi Institute of International Trade and Commerce, Xian Yang 712046, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Du
authors.affiliation: a Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an 710069, China.|b Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China.
authors.forename: Quan-Wang
authors.initials: QW
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an 710069, China.|b Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China.
authors.forename: Yasir
authors.initials: Y
authors.lastname: Arfat
authors.affiliation: a Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an 710069, China.|b Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Dang
authors.affiliation: a Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an 710069, China.|b Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China.
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004794:Enzyme Repression / Q000187:drug effects; D005260:Female; D019417:Hindlimb Suspension / Q000009:adverse effects; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020966:Muscular Disorders, Atrophic / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D011719:Pyrazines / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D063150:Polycomb Repressive Complex 1; C570469:Ring1 protein, rat; D044767:Ubiquitin-Protein Ligases; C017953:tetramethylpyrazine
keywords: apoptose; apoptosis; atrophie par inaction; cytosolic calcium overload; disuse atrophy; oxidative stress; stress oxydatif; surcharge cytosolique de calcium; tetramethylpyrazine; tétraméthylpyrazine