Hirasaka Katsuya, Saito Shinobu, Yamaguchi Saki, Miyazaki Riho, Wang Yao, Haruna Marie, Taniyama Shigeto, Higashitani Atsushi, Terao Junji, Nikawa Takeshi, Tachibana Katsuyasu
Graduate School of Fisheries and Environmental Sciences, Nagasaki University.
J Nutr Sci Vitaminol (Tokyo). 2016;62(3):178-84. doi: 10.3177/jnsv.62.178.
Proinflammatory cytokines contribute to the progression of muscle wasting caused by ubiquitin-proteasome-dependent proteolysis. We have previously demonstrated that isoflavones, such as genistein and daidzein, prevent TNF-α-induced muscle atrophy in C2C12 myotubes. In this study, we examined the effect of dietary flavonoids on the wasting of muscle. Mice were divided into the following four groups: vehicle-injected (control) mice fed the normal diet (CN); tumor-bearing mice fed the normal diet (TN); control mice fed the isoflavone diet (CI); and tumor-bearing mice fed the isoflavone diet (TI). There were no significant differences in the intake of food or body weight gain among these four groups. The wet weight and myofiber size of gastrocnemius muscle in TN significantly decreased, compared with those in CN. Interestingly, the wet weight and myofiber size of gastrocnemius muscle in TI were nearly the same as those in CN and CI, although isoflavone supplementation did not affect the increased tumor mass or concentrations of proinflammatory cytokines, such as TNF-α and IL-6, in the blood. Moreover, increased expression of muscle-specific ubiquitin ligase genes encoding MAFbx/Atrogin-1 and MuRF1 in the skeletal muscle of TN was significantly inhibited by the supplementation of isoflavones. In parallel with the expression of muscle-specific ubiquitin ligases, dietary isoflavones significantly suppressed phosphorylation of ERK in tumor-bearing mice. These results suggest that dietary isoflavones improve muscle wasting in tumor-bearing mice via the ERK signaling pathway mediated-suppression of ubiquitin ligases in muscle cells.
促炎细胞因子会导致由泛素-蛋白酶体依赖性蛋白水解引起的肌肉萎缩进展。我们之前已经证明，染料木黄酮和大豆苷元等异黄酮可预防TNF-α诱导的C2C12肌管中的肌肉萎缩。在本研究中，我们研究了膳食黄酮类化合物对肌肉消瘦的影响。将小鼠分为以下四组：注射溶剂（对照）的正常饮食喂养小鼠（CN）；正常饮食喂养的荷瘤小鼠（TN）；异黄酮饮食喂养的对照小鼠（CI）；以及异黄酮饮食喂养的荷瘤小鼠（TI）。这四组小鼠在食物摄入量或体重增加方面没有显著差异。与CN组相比，TN组腓肠肌的湿重和肌纤维大小显著降低。有趣的是，TI组腓肠肌的湿重和肌纤维大小与CN组和CI组几乎相同，尽管补充异黄酮并未影响血液中肿瘤质量的增加或促炎细胞因子如TNF-α和IL-6的浓度。此外,补充异黄酮可显著抑制TN组骨骼肌中编码MAFbx/Atrogin-1和MuRF1的肌肉特异性泛素连接酶基因的表达增加。与肌肉特异性泛素连接酶的表达平行，膳食异黄酮显著抑制荷瘤小鼠中ERK的磷酸化。这些结果表明，膳食异黄酮通过ERK信号通路介导的肌肉细胞中泛素连接酶的抑制作用来改善荷瘤小鼠的肌肉消瘦。
