| Autor: |
Petrov AM; Institute of Neuroscience, Kazan State Medical University, Butlerova st. 49, 420012 Kazan, Russia. fysio@rambler.ru.; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', P. O. Box 30, Lobachevsky Str., 2/31, 420111 Kazan, Russia. fysio@rambler.ru., Shalagina MN; Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, 426034 Izhevsk, Russia. uvula@mail.ru., Protopopov VA; Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, 426034 Izhevsk, Russia. vladimirvst@yandex.ru., Sergeev VG; Department of Physiology, Cell Biology and Biotechnology, Institute of Natural Science, Udmurt State University, University St. 1, 426034 Izhevsk, Russia. cellbio@yandex.ru., Ovechkin SV; Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, 426034 Izhevsk, Russia. ovechkin-sv@mail.ru., Ovchinina NG; Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, 426034 Izhevsk, Russia. ntly.82@mail.ru., Sekunov AV; Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, 426034 Izhevsk, Russia. d1key@inbox.ru., Zefirov AL; Institute of Neuroscience, Kazan State Medical University, Butlerova st. 49, 420012 Kazan, Russia. zefiroval@rambler.ru., Zakirjanova GF; Institute of Neuroscience, Kazan State Medical University, Butlerova st. 49, 420012 Kazan, Russia. gffysiology@gmail.com.; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', P. O. Box 30, Lobachevsky Str., 2/31, 420111 Kazan, Russia. gffysiology@gmail.com., Bryndina IG; Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, 426034 Izhevsk, Russia. i_bryndina@mail.ru. |
| Abstrakt: |
Lipid raft disruption is an early event during skeletal muscle unloading. Ceramide (Cer) serves as a signaling lipid that can contribute to lipid raft disturbance and muscle atrophy. Using biochemical and fluorescent approaches, the distribution of Cer and related molecules in the rat soleus muscle subjected to 12 h of hindlimb suspension (HS) was studied. HS led to upregulation of TNFα receptor 1 (TNFR1), Cer-producing enzymes, and acid and neutral sphingomyelinase (SMase) in detergent-resistant membranes (lipid rafts), which was accompanied by an increase in Cer and a decrease in sphingomyelin in this membrane fraction. Fluorescent labeling indicated increased Cer in the sarcoplasm as well as the junctional (synaptic) and extrajunctional compartments of the suspended muscles. Also, a loss of membrane asymmetry (a hallmark of membrane disturbance) was induced by HS. Pretreatment with clomipramine, a functional inhibitor of acid SMase, counteracted HS-mediated changes in the Cer/sphingomyelin ratio and acid SMase abundance as well as suppressed Cer accumulation in the intracellular membranes of junctional and extrajunctional regions. However, the elevation of plasma membrane Cer and disturbance of the membrane asymmetry were suppressed only in the junctional compartment. We suggest that acute HS leads to TNFR1 and SMase upregulation in the lipid raft fraction and deposition of Cer throughout the sarcolemma and intracellularly. Clomipramine-mediated downregulation of acid SMase can suppress Cer accumulation in all compartments, excluding the extrajunctional plasma membrane. |
