Krapf Solveig, Schjølberg Tiril, Asoawe Lucia, Honkanen Susanna Kyllikki, Kase Eili Tranheim, Thoresen G Hege, Haugen Fred
Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
National Institute of Occupational Health, Oslo, Norway.
J Therm Biol. 2021 May;98:102930. doi: 10.1016/j.jtherbio.2021.102930. Epub 2021 Apr 15.
Proteins secreted from skeletal muscle serving a signalling role have been termed myokines. Many of the myokines are exercise factors, produced and released in response to muscle activity. Cold exposures affecting muscle may occur in recreational, occupational and therapeutic settings. Whether muscle temperature independently affects myokine profile, is still to be elucidated. We hypothesized that manipulating muscle temperature by means of external cooling would change myokine production and release. In the present study we have established new models for cold exposure of muscle in vivo and in vitro where rat hind limb or cultured human myotubes were cooled to 18 °C. After a recovery period, muscle tissue, cells and culture media were harvested for further analysis by qPCR and immunoassays. Expression of several myokine genes were significantly increased after cold exposure in both models: in rat muscle, mRNA levels of CCL2 (p = 0.04), VEGFA (p = 0.02), CXCL1 (p = 0.02) and RBM3 (p = 0.02) increased while mRNA levels of IL-6 (p = 0.03) were decreased; in human myotubes, mRNA levels of IL6 (p = 0.01), CXCL8 (p = 0.04), VEGFA (p = 0.03) and CXCL1 (p < 0.01) were significantly increased, as well as intracellular protein levels of IL-8 (CXCL8 gene product; p < 0.01). The corresponding effect on myokine secretion was not observed, on the contrary, IL-8 (p = 0.02) and VEGF (VEGFA gene product) p < 0.01) concentrations in culture media were reduced after cold exposure in vitro. In conclusion, cold exposure of muscle in vivo and in vitro had an effect on the production and release of several known exercise-related myokines. Myokine expression at the level of mRNA and protein was increased by cold exposure, whereas secretion tended to be decreased.
从骨骼肌分泌并发挥信号传导作用的蛋白质被称为肌动蛋白。许多肌动蛋白都是运动因子，它们是因肌肉活动而产生和释放的。在娱乐、职业和治疗环境中都可能发生影响肌肉的冷暴露情况。肌肉温度是否独立影响肌动蛋白谱仍有待阐明。我们假设通过外部冷却来控制肌肉温度会改变肌动蛋白的产生和释放。在本研究中，我们建立了新的体内和体外肌肉冷暴露模型，将大鼠后肢或培养的人肌管冷却至18°C。经过恢复期后，收集肌肉组织、细胞和培养基，通过qPCR和免疫测定进行进一步分析。在两种模型中，冷暴露后几种肌动蛋白基因的表达均显著增加：在大鼠肌肉中，CCL2（p = 0.04）、VEGFA（p = 0.02）、CXCL1（p = 0.02）和RBM3（p = 0.02）的mRNA水平升高，而IL-6（p = 0.03）的mRNA水平降低；在人肌管中，IL6（p = 0.01）、CXCL8（p = 0.04）、VEGFA（p = 0.03）和CXCL1（p < 0.01）的mRNA水平显著升高，以及IL-8（CXCL8基因产物；p < 0.01）的细胞内蛋白质水平也显著升高。未观察到对肌动蛋白分泌的相应影响，相反，体外冷暴露后培养基中IL-8（p = 0.02）和VEGF（VEGFA基因产物；p < 0.01）的浓度降低。总之，体内和体外的肌肉冷暴露对几种已知的与运动相关的肌动蛋白的产生和释放有影响。冷暴露会增加mRNA和蛋白质水平的肌动蛋白表达，而分泌则趋于减少。
