Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension

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...

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Main Authors: Irina G. Bryndina, Maria N. Shalagina, Vladimir A. Protopopov, Alexey V. Sekunov, Andrey L. Zefirov, Guzalia F. Zakirjanova, Alexey M. Petrov
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/5/2239
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author Irina G. Bryndina
Maria N. Shalagina
Vladimir A. Protopopov
Alexey V. Sekunov
Andrey L. Zefirov
Guzalia F. Zakirjanova
Alexey M. Petrov
author_facet Irina G. Bryndina
Maria N. Shalagina
Vladimir A. Protopopov
Alexey V. Sekunov
Andrey L. Zefirov
Guzalia F. Zakirjanova
Alexey M. Petrov
author_sort Irina G. Bryndina
collection DOAJ
description 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.
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spelling doaj.art-3ecaef4e3c704860b435c9ba054a67f32023-12-11T18:12:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225223910.3390/ijms22052239Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb SuspensionIrina G. Bryndina0Maria N. Shalagina1Vladimir A. Protopopov2Alexey V. Sekunov3Andrey L. Zefirov4Guzalia F. Zakirjanova5Alexey M. Petrov6Department of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, Izhevsk 426034, RussiaDepartment of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, Izhevsk 426034, RussiaDepartment of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, Izhevsk 426034, RussiaDepartment of Pathophysiology and Immunology, Izhevsk State Medical Academy, Kommunarov St. 281, Izhevsk 426034, RussiaInstitute of Neuroscience, Kazan State Medical University, Butlerova St. 49, Kazan 420012, RussiaInstitute of Neuroscience, Kazan State Medical University, Butlerova St. 49, Kazan 420012, RussiaInstitute of Neuroscience, Kazan State Medical University, Butlerova St. 49, Kazan 420012, RussiaMuscle 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.https://www.mdpi.com/1422-0067/22/5/2239skeletal muscledisusedenervationdeafferentationcapsaicinlipid rafts
spellingShingle Irina G. Bryndina
Maria N. Shalagina
Vladimir A. Protopopov
Alexey V. Sekunov
Andrey L. Zefirov
Guzalia F. Zakirjanova
Alexey M. Petrov
Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension
International Journal of Molecular Sciences
skeletal muscle
disuse
denervation
deafferentation
capsaicin
lipid rafts
title Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension
title_full Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension
title_fullStr Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension
title_full_unstemmed Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension
title_short Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension
title_sort early lipid raft related changes interplay between unilateral denervation and hindlimb suspension
topic skeletal muscle
disuse
denervation
deafferentation
capsaicin
lipid rafts
url https://www.mdpi.com/1422-0067/22/5/2239
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AT alexeyvsekunov earlylipidraftrelatedchangesinterplaybetweenunilateraldenervationandhindlimbsuspension
AT andreylzefirov earlylipidraftrelatedchangesinterplaybetweenunilateraldenervationandhindlimbsuspension
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