Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, Izhevsk 426034, Russia.
Institute of Neuroscience, Kazan State Medical University, Butlerova St. 49, Kazan 420012, Russia.
Int J Mol Sci. 2021 Feb 24;22(5):2239. doi: 10.3390/ijms22052239.
Muscle disuse and denervation leads to muscle atrophy, but underlying mechanisms can be different. Previously, we have found ceramide (Cer) accumulation and lipid raft disruption after acute hindlimb suspension (HS), a model of muscle disuse. Herein, using biochemical and fluorescent approaches the influence of unilateral denervation itself and in combination with short-term HS on membrane-related parameters of rat soleus muscle was studied. Denervation increased immunoexpression of sphingomyelinase and Cer in plasmalemmal regions, but decreased Cer content in the raft fraction and enhanced lipid raft integrity. Preliminary denervation suppressed (1) HS-induced Cer accumulation in plasmalemmal regions, shown for both nonraft and raft-fractions; (2) HS-mediated decrease in lipid raft integrity. Similar to denervation, inhibition of the sciatic nerve afferents with capsaicin itself increased Cer plasmalemmal immunoexpression, but attenuated the membrane-related effects of HS. Finally, both denervation and capsaicin treatment increased immunoexpression of proapoptotic protein Bax and inhibited HS-driven increase in antiapoptotic protein Bcl-2. Thus, denervation can increase lipid raft formation and attenuate HS-induced alterations probably due to decrease of Cer levels in the raft fraction. The effects of denervation could be at least partially caused by the loss of afferentation. The study points to the importance of motor and afferent inputs in control of Cer distribution and thereby stability of lipid rafts in the junctional and extrajunctional membranes of the muscle.
肌肉废用和去神经支配导致肌肉萎缩，但潜在的机制可能不同。之前，我们已经发现急性后肢悬吊（HS）后，即肌肉废用模型中，神经酰胺（Cer）积累和脂筏破坏。在此，我们使用生化和荧光方法研究了单侧去神经支配本身及其与短期 HS 联合对大鼠比目鱼肌膜相关参数的影响。去神经支配增加了质膜区域中神经鞘磷脂酶和 Cer 的免疫表达，但降低了筏分数中的 Cer 含量并增强了脂筏的完整性。初步去神经支配抑制了（1）HS 诱导的质膜区域 Cer 积累，这在非筏和筏分数中均有表现；（2）HS 介导的脂筏完整性降低。与去神经支配相似，用辣椒素来抑制坐骨神经传入纤维本身增加了质膜 Cer 的免疫表达，但减弱了 HS 的膜相关效应。最后，去神经支配和辣椒素处理都增加了促凋亡蛋白 Bax 的免疫表达，并抑制了 HS 驱动的抗凋亡蛋白 Bcl-2 的增加。因此，去神经支配可以增加脂筏的形成，并减轻 HS 诱导的改变，这可能是由于筏分数中的 Cer 水平降低所致。去神经支配的影响至少部分可能是由于传入神经的丧失所致。该研究指出了运动和传入输入在控制 Cer 分布以及肌肉连接和连接外膜中脂筏稳定性方面的重要性。
