Ohira Takashi, Higashibata Akira, Seki Masaya, Kurata Yoichi, Kimura Yayoi, Hirano Hisashi, Kusakari Yoichiro, Minamisawa Susumu, Kudo Takashi, Takahashi Satoru, Ohira Yoshinobu, Furukawa Satoshi
Division of Aerospace Medicine, Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan
Space Biomedical Research Group, Japan Aerospace Exploration Agency, Tsukuba, Ibaraki, Japan.
Physiol Rep. 2017 Aug;5(15). doi: 10.14814/phy2.13350.
The effects of heat stress on the morphological properties and intracellular signaling of innervated and denervated soleus muscles were investigated. Heat stress was applied to rats by immersing their hindlimbs in a warm water bath (42°C, 30 min/day, every other day following unilateral denervation) under anesthesia. During 14 days of experimental period, heat stress for a total of seven times promoted growth-related hypertrophy in sham-operated muscles and attenuated atrophy in denervated muscles. In denervated muscles, the transcription of ubiquitin ligase, atrogin-1/muscle atrophy F-box (), and muscle RING-finger protein-1 (), genes was upregulated and ubiquitination of proteins was also increased. Intermittent heat stress inhibited the upregulation of , but not transcription. And the denervation-caused reduction in phosphorylated protein kinase B (Akt), 70-kDa heat-shock protein (HSP70), and peroxisome proliferator-activated receptor coactivator-1 (PGC-1), which are negative regulators of and transcription, was mitigated. In sham-operated muscles, repeated application of heat stress did not affect and transcription, but increased the level of phosphorylated Akt and HSP70, but not PGC-1 Furthermore, the phosphorylation of Akt and ribosomal protein S6, which is known to stimulate protein synthesis, was increased immediately after a single heat stress particularly in the sham-operated muscles. The effect of a heat stress was suppressed in denervated muscles. These results indicated that the beneficial effects of heat stress on the morphological properties of muscles were brought regardless of innervation. However, the responses of intracellular signaling to heat stress were distinct between the innervated and denervated muscles.
研究了热应激对受神经支配和去神经支配的比目鱼肌形态学特性及细胞内信号传导的影响。在麻醉状态下,将大鼠后肢浸入温水浴(42℃,每天30分钟,单侧去神经支配后隔天进行)对其施加热应激。在14天的实验期内,总共7次的热应激促进了假手术肌肉中与生长相关的肥大,并减轻了去神经支配肌肉的萎缩。在去神经支配的肌肉中,泛素连接酶atrogin-1/肌肉萎缩F盒()和肌肉环指蛋白-1()基因的转录上调,蛋白质的泛素化也增加。间歇性热应激抑制了的上调,但不影响转录。并且,去神经支配导致的磷酸化蛋白激酶B(Akt)、70 kDa热休克蛋白(HSP70)和过氧化物酶体增殖物激活受体γ共激活因子-1(PGC-1)的减少得到缓解,这些都是和转录的负调节因子。在假手术肌肉中,重复施加热应激不影响和转录,但增加了磷酸化Akt和HSP70的水平,但不影响PGC-1。此外,已知能刺激蛋白质合成的Akt和核糖体蛋白S6的磷酸化在单次热应激后立即增加,特别是在假手术肌肉中。去神经支配的肌肉中热应激的作用受到抑制。这些结果表明,无论神经支配情况如何,热应激对肌肉形态学特性都有有益影响。然而,受神经支配和去神经支配的肌肉对热应激的细胞内信号反应是不同的。