Ceramide Enriched Membrane Domains in Rat Skeletal Muscle Exposed to Short-Term Hypogravitational Unloading

Брындина, И. Г.; Protopopov, V. A.; Sergeev, Valery; Shalagina, Maria N.; Ovechkin, Sergey; Yakovlev, A. A.

doi:10.3389/conf.fphys.2018.26.00028

Cited by 6 publications

(9 citation statements)

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“…While in the control animals ceramide staining was characterized by the weak diffuse fluorescence, located preferentially in the region of the plasma membrane, in unloaded muscle this image was very different. Ceramide accumulated in the form of large superficial structures resembled ceramide-enriched membrane domains described earlier by[28] and found by us in rat soleus muscle suspended for 4 days[41]. Clomipramine treatment was effective in partial prevention of ceramide membraneTNFR1 aSMase nSMase GAPDH rearrangement due to disuse.…”

supporting

confidence: 79%

“…This effect has been described in different cells [58,59,60]. Previously we observed the formation of ceramideenriched domains in the plasma membranes of disused rat soleus muscle [41]. Another important aspect of pro-oxidant action of ceramide is that it exerts a direct effect on the generation of reactive oxygen species in mitochondria [61].…”

Section: Discussionmentioning

confidence: 57%

“…We have shown previously that lipid raft disorganization in rat soleus muscle caused by shortterm unloading (12 hours) is associated with aSMase/ceramide up-regulation [6,19]. Also, we have demonstrated that not only ceramide amount but its distribution in muscle fibers substantially renders during disuse [41]. In the present work, we studied the intensity and distribution of ceramide immunofluorescence in longitudinal sections of rat soleus muscle that underwent 4-or 14-day unloading with or without clomipramine treatment.…”

Section: Ceramide (Biochemical and Immunofluorescence Study)mentioning

confidence: 85%

“…Analogously, we have supposed that the de novo synthesis is not the main source of ceramide accumulation in disused muscle because we did not find its up-regulation in soleus muscle of mice that underwent HS (Bryndina, 2014). In addition, we have shown that the inhibitor of acid sphingomyelinase clomipramine prevents or attenuates some effects of muscle disuse, like following: ceramide accumulation [46], lipid raft disruption [19], formation of ceramideenriched membrane domains [41], as well as the disturbance of membrane lipid asymmetry and formation of ceramide-containing vesicles [6]. Thus, we believe that aSMase mechanism is predominant in ceramide generation during disuse and it may be involved in the development of disuse muscle atrophy.…”

Section: Discussionmentioning

confidence: 99%

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TNFa is Involved in the Development of Disuse Muscle Atrophy Through the Acid Sphingomyelinase/ Ceramide Up-Regulation and Pro-Oxidant Signaling

Брындина

Ovchinina

Protopopov

et al. 2020

Preprint

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Background: There is paucity of data indicating the role of cytokines including TNFa in the development of disuse muscle atrophy, despite the growing interest to this problem emerging in the recent years. The aim of the present study was to test the hypothesis that TNFa/ TNFR1 may be involved in the development of disuse muscle atrophy caused by unloading through aSMase/ ceramide/ ROS mechanism. Methods: The experiments were performed on male Wistar rats (180 – 230g) subjected to 4 or 14 days of hindlimb suspension (HS) and treated with clomipramine (HS+Clom) or vehicle. The following parameters were studied: TNFR1, aSMase, nSMase and Nox2 proteins and ceramide in detergent-resistant membrane (DRM) fraction isolated from soleus muscle homogenates, pro-oxidant/anti-oxidant and pro-apoptotic/anti-apoptotic activities, immune fluorescence intensity and distribution of ceramide, Nox2, Nox4 and caveolin-3 on longitudinal and transverse muscle sections. The relative muscle mass, cross-sectional area (CSA) and Feret’s diameter (FD) of muscle fibers were used to confirm muscle atrophy. Statistical analysis was performed using one-way ANOVA followed by the Bonferroni post hoc test, or Cruskall-Wallis and Mann-Whitney U test. Results: Disuse caused an increase in membrane TNFR1, aSMase, ceramide abundance in DRM, up-regulation of pro-oxidant and pro-apoptotic capacities (increased Nox2, Nox4, TBA-active products, Bax/Bcl-2 ratio, elevated activity of caspase-3/7 and -6). The most of alterations were maximal on the 4 th day of unloading. The inhibitor of aSMase clomipramine attenuated ceramide accumulation, decreased pro-oxidant and pro-apoptotic activities and diminished muscle atrophy induced by unloading. It has been shown that in suspended for 14 days rats the loss in relative muscle mass, CSA and FD averaged -35%, -65% and -49%, respectively, whereas in clomipramine treated rats it was -25%, -45% and -25%, in comparison with the control values. Clomipramine also mitigated the inhibition of the mTORC1/p70S6 kinase inhibition caused by 14-day HS. Conclusions: The obtained results indicate the involvement of aSMase/ ceramide pathway in the development of disuse muscle atrophy. This effect may be triggered by TNFR1 and realized through enhanced prooxidant NADPH oxidase activity and pro-apoptotic signaling.

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supporting

confidence: 79%

Section: Discussionmentioning

confidence: 57%

Section: Ceramide (Biochemical and Immunofluorescence Study)mentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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TNFa is Involved in the Development of Disuse Muscle Atrophy Through the Acid Sphingomyelinase/ Ceramide Up-Regulation and Pro-Oxidant Signaling

Брындина

Ovchinina

Protopopov

et al. 2020

Preprint

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“…However, such data in humans are inconsistent (Skovbro et al 2008;Bosma et al 2012;Petersen & Jurczak, 2016). Although many rodent studies have shown ceramide accumulation with muscle disuse (Bryndina et al 2014;Lee et al 2015;Kwon et al 2016;Bryndina et al 2018), a recent clinical trial demonstrated that skeletal muscle lipid intermediates did not increase after 7 days of bed rest in young healthy adults (Dirks et al 2016). However, gaps with respect to unravelling the relationship between ceramides and inactivity-induced insulin resistance remain.…”

Section: Introductionmentioning

confidence: 99%

Skeletal muscle ceramides and relationship with insulin sensitivity after 2 weeks of simulated sedentary behaviour and recovery in healthy older adults

Reidy

McKenzie

Mahmassani

et al. 2018

The Journal of Physiology

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Older adults are at risk of physical inactivity as they encounter debilitating life events. It is not known how insulin sensitivity is affected by modest short-term physical inactivity and recovery in healthy older adults, nor how insulin sensitivity is related to changes in serum and muscle ceramide content. Healthy older adults (aged 64-82 years, five females, seven males) were assessed before (PRE), after 2 weeks of reduced physical activity (RA) and following 2 weeks of recovery (REC). Insulin sensitivity (hyperinsulinaemic-euglyceamic clamp), lean mass, muscle function, skeletal muscle subfraction, fibre-specific, and serum ceramide content and indices of skeletal muscle inflammation were assessed. Insulin sensitivity decreased by 15 ± 6% at RA (driven by men) but rebounded above PRE by 14 ± 5% at REC. Mid-plantar flexor muscle area and leg strength decreased with RA, although only muscle size returned to baseline levels following REC. Body fat did not change and only minimal changes in muscle inflammation were noted across the intervention. Serum and intramuscular ceramides (nuclear/myofibrillar fraction) were modestly increased at RA and REC. However, ceramides were not related to changes in inactivity-induced insulin sensitivity in healthy older adults. Short-term inactivity induced insulin resistance in older adults in the absence of significant changes in body composition (i.e. fat mass) are not related to changes in ceramides.

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Muscle Plasticity under Functional Unloading: Effects of an Acid Sphingomyelinase Inhibitor Clomipramine

Sekunov

Protopopov

Skurygin

et al. 2021

J Evol Biochem Phys

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Ceramide Enriched Membrane Domains in Rat Skeletal Muscle Exposed to Short-Term Hypogravitational Unloading

Cited by 6 publications

References 0 publications

TNFa is Involved in the Development of Disuse Muscle Atrophy Through the Acid Sphingomyelinase/ Ceramide Up-Regulation and Pro-Oxidant Signaling

TNFa is Involved in the Development of Disuse Muscle Atrophy Through the Acid Sphingomyelinase/ Ceramide Up-Regulation and Pro-Oxidant Signaling

Skeletal muscle ceramides and relationship with insulin sensitivity after 2 weeks of simulated sedentary behaviour and recovery in healthy older adults

Muscle Plasticity under Functional Unloading: Effects of an Acid Sphingomyelinase Inhibitor Clomipramine

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