Tetramethylpyrazine ameliorated disuse-induced gastrocnemius muscle atrophy in hindlimb unloading rats through suppression of Ca2+/ROS-mediated apoptosis.
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.
['Hu|Nai-Fei|NF|', 'Chang|Hui|H|', 'Du|Bei|B|', 'Zhang|Quan-Wang|QW|', 'Arfat|Yasir|Y|', 'Dang|Kai|K|', 'Gao|Yun-Fang|YF|']
D000818:Animals D017209:Apoptosis D015415:Biomarkers D020013:Calcium Signaling D004794:Enzyme Repression D005260:Female D019417:Hindlimb Suspension D018656:Muscle Fibers, Fast-Twitch D018657:Muscle Fibers, Slow-Twitch D018482:Muscle, Skeletal D020966:Muscular Disorders, Atrophic D018384:Oxidative Stress D010975:Platelet Aggregation Inhibitors D063150:Polycomb Repressive Complex 1 D059748:Proteolysis D011719:Pyrazines D011897:Random Allocation D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D044767:Ubiquitin-Protein Ligases D014665:Vasodilator Agents
tetramethylpyrazine apoptosis disuse atrophy oxidative stress cytosolic calcium overload apoptose atrophie par inaction stress oxydatif surcharge cytosolique de calcium tétraméthylpyrazine