Protective effects of an inducer of molecular chaperon on disuse skeletal muscle

香叶基香叶基丙酮（GGA）作为胃溃疡和胃炎的治疗药物已在临床上应用多年。GGA选择性诱导70-kDa热休克蛋白（HSP 70），并且HSP在所有细胞和生物体中暴露于许多应激后作为适应性反应被诱导。热休克蛋白作为分子伴侣参与蛋白质的正确折叠和重折叠，从而发挥必要的管家和保护功能。因此，在本研究中，我们研究了GGA对骨骼肌在正常和应激条件下，如废用性萎缩大鼠后肢卸载的影响。在给予0、200、400和600 mg/kg的GGA后24小时分离骨骼肌。在比目鱼肌、腓肠肌、跖肌和趾长伸肌中，将剂量增加至600 mg/kg并没有导致HSP 72表达的进一步增加。当暴露于压力时，GGA引发其他类型的细胞增强HSP 70的诱导。此外，我们研究了在后肢去负荷条件下给予GGA后对HSP 70的诱导作用。与对照组相比，萎缩肌肉中的HSP 72水平降低，而GGA给药肌肉中的这些值减弱了后肢卸载条件下HSP 70的降低。虽然后肢卸载导致肌肉萎缩，肌原纤维蛋白含量的损失显着减少GGA管理的骨骼肌。这些结果表明，GGA可能表现出独立的Hsp 70诱导的保护作用。此外，这些观察结果也可能表明，GGA的管理可能是一个有用的工具，以减轻肌肉萎缩。

Geranylgeranylacetone (GGA) has been used in clinics for many years as a therapeutic agent for gastric ulcer and gastritis. GGA induces 70-kDa heat shock protein (HSP70) selectively, and HSPs are induced as an adaptative response in all cells and organisms upon exposure to a number of stresses. HSPs function as molecular chaperones involved in the correct folding and refolding of proteins, and thereby exert essential housekeeping and protective functions. In this study, we thus investigated the effects of GGA on skeletal muscle under normal and stressful conditions such as disuse atrophy by hindlimb unloading in rats. Skeletal muscles were isolated 24 hours after administration of GGA at 0,200,400 and 600 mg/kg. In soleus, gastrocnemius, plantaris and extensor digitorum longus muscles, increasing the dose up to 600 mg/kg did not result in a further increase in HSP72 expression. GGA primed other types of cells for enhanced induction of HSP70, when exposed to stress. In addition, we investigated the induction of HSP70 after administration of GGA in hindlimb unloading condition. The HSP72 levels decreased in the atrophied muscle compare with control, whereas these values in the GGA administrated muscles attenuated the decrease of HSP70 in hindlimb unloading condition. Although hindlimb unloading resulted in muscle atrophy, the loss of myofibrillar protein content was significantly less in the GGA administrated skeletal muscle. These results suggest that GGA may exhibit protective actions independently of Hsp70 induction. Additionally, these observations may also indicate that the administration of GGA could be one of the useful tools to attenuate muscle atrophy.