Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain.
Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain.
Nutrients. 2020 Jan 31;12(2):388. doi: 10.3390/nu12020388.
We hypothesized that curcumin may mitigate muscle protein degradation and loss through attenuation of proteolytic activity in limb muscles of mice exposed to reloading (7dR) following immobilization (7dI). In gastrocnemius of mice (female C57BL/6J, 10 weeks) exposed to recovery following a seven-day period of hindlimb immobilization with/without curcumin treatment, markers of muscle proteolysis (systemic troponin-I), atrophy signaling pathways and histone deacetylases, protein synthesis, and muscle phenotypic characteristics and function were analyzed. In gastrocnemius of reloading mice compared to unloaded, muscle function, structure, sirtuin-1, and protein synthesis improved, while proteolytic and signaling markers (FoxO1/3) declined. In gastrocnemius of unloaded and reloaded mice treated with curcumin, proteolytic and signaling markers (NF-kB p50) decreased and sirtuin-1 activity and hybrid fibers size increased (reloaded muscle), while no significant improvement was seen in muscle function. Treatment with curcumin elicited a rise in sirtuin-1 activity, while attenuating proteolysis in gastrocnemius of mice during reloading following a period of unloading. Curcumin attenuated muscle proteolysis probably via activation of histone deacetylase sirtuin-1, which also led to decreased levels of atrophy signaling pathways. These findings offer an avenue of research in the design of therapeutic strategies in clinical settings of patients exposed to periods of disuse muscle atrophy.
我们假设姜黄素可能通过减轻在固定（7dI）后再加载（7dR）的肢体肌肉中的蛋白水解活性来减轻肌肉蛋白降解和损失。在接受了为期七天的后肢固定后恢复的小鼠（雌性 C57BL/6J，10 周）的比目鱼肌中，分析了肌肉蛋白水解（全身肌钙蛋白-I）、萎缩信号通路和组蛋白去乙酰化酶、蛋白质合成以及肌肉表型特征和功能的标志物。与未加载相比，再加载小鼠的比目鱼肌中的肌肉功能、结构、Sirtuin-1 和蛋白质合成得到改善，而蛋白水解和信号标志物（FoxO1/3）下降。在未加载和再加载并用姜黄素治疗的小鼠的比目鱼肌中，蛋白水解和信号标志物（NF-kB p50）下降，Sirtuin-1 活性和杂种纤维大小增加（再加载肌肉），而肌肉功能没有明显改善。姜黄素的治疗引发了 Sirtuin-1 活性的上升，同时减轻了再加载后卸载期后小鼠比目鱼肌中的蛋白水解。姜黄素可能通过激活组蛋白去乙酰化酶 Sirtuin-1 来减轻肌肉蛋白水解，这也导致了萎缩信号通路水平的降低。这些发现为在暴露于肌肉失用性萎缩的患者的临床环境中设计治疗策略的研究提供了途径。
