Bryndina Irina G, Shalagina Maria N, Sekunov Alexey V, Zefirov Andrei L, Petrov Alexey M
Department of Pathological Physiology, Izhevsk State Medial Academy, Izhevsk, Kommunarov St. 281, 426034, Russia.
Department of Normal Physiology, Kazan State Medial University, Kazan, Butlerova St. 49, 420012, Russia.
Neurosci Lett. 2018 Jan 18;664:1-6. doi: 10.1016/j.neulet.2017.11.009. Epub 2017 Nov 7.
Disuse-induced skeletal muscle dysfunction is a serious consequence of long-term spaceflight, numerous diseases and conditions for which treatment possibilities are still strictly limited. We have previously shown that acute hindlimb suspension (HS)-mediated disuse disrupts membrane lipid rafts in the unloaded muscle. Here, we investigated whether pretreatment of rats with the inhibitor of acid sphingomyelinase, clomipramine (1.25mg/g/day, intramuscularly, for 5days before HS), is able to hinder the loss in lipid raft integrity in response to 12h of HS. Clomipramine pretreatment significantly counteracted the decrease in labeling of the plasma membranes with lipid raft markers (fluorescent cholera toxin B subunit and bodipy-GM1-ganglioside) specifically in the junctional regions of the suspended soleus muscle. This was associated with: a) enhancing raft disrupting potential of exogenous sphingomyelinase in the junctional membranes; b) prevention of both ceramide accumulation and cholesterol loss; c) prevention of decline in nicotinic acetylcholine receptor labeling in the unloaded muscle. Our data suggest that sphingomyelinase-mediated raft disturbance serves as one of the earlier events in HS effects.
废用性骨骼肌功能障碍是长期太空飞行、众多疾病和病症的严重后果，而针对这些病症的治疗可能性仍然极为有限。我们之前已经表明，急性后肢悬吊（HS）介导的废用会破坏卸载肌肉中的膜脂筏。在此，我们研究了用酸性鞘磷脂酶抑制剂氯米帕明（1.25mg/g/天，肌肉注射，在HS前5天）预处理大鼠是否能够阻止因12小时HS而导致的脂筏完整性丧失。氯米帕明预处理显著抵消了用脂筏标记物（荧光霍乱毒素B亚基和Bodipy-GM1-神经节苷脂）标记悬吊带比目鱼肌连接区域质膜的减少。这与以下情况相关：a）增强外源性鞘磷脂酶在连接膜中的脂筏破坏潜力；b）防止神经酰胺积累和胆固醇流失；c）防止卸载肌肉中烟碱型乙酰胆碱受体标记的下降。我们的数据表明，鞘磷脂酶介导的脂筏紊乱是HS效应中较早发生的事件之一。
