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

2021 ◽  
Vol 22 (5) ◽  
pp. 2239
Author(s):  
Irina G. Bryndina ◽  
Maria N. Shalagina ◽  
Vladimir A. Protopopov ◽  
Alexey V. Sekunov ◽  
Andrey L. Zefirov ◽  
...  

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.

2019 ◽  
Vol 20 (19) ◽  
pp. 4860 ◽  
Author(s):  
Alexey M. Petrov ◽  
Maria N. Shalagina ◽  
Vladimir A. Protopopov ◽  
Valeriy G. Sergeev ◽  
Sergey V. Ovechkin ◽  
...  

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.


2021 ◽  
Vol 22 (8) ◽  
pp. 3920
Author(s):  
Violetta V. Kravtsova ◽  
Inna I. Paramonova ◽  
Natalia A. Vilchinskaya ◽  
Maria V. Tishkova ◽  
Vladimir V. Matchkov ◽  
...  

Sustained sarcolemma depolarization due to loss of the Na,K-ATPase function is characteristic for skeletal muscle motor dysfunction. Ouabain, a specific ligand of the Na,K-ATPase, has a circulating endogenous analogue. We hypothesized that the Na,K-ATPase targeted by the elevated level of circulating ouabain modulates skeletal muscle electrogenesis and prevents its disuse-induced disturbances. Isolated soleus muscles from rats intraperitoneally injected with ouabain alone or subsequently exposed to muscle disuse by 6-h hindlimb suspension (HS) were studied. Conventional electrophysiology, Western blotting, and confocal microscopy with cytochemistry were used. Acutely applied 10 nM ouabain hyperpolarized the membrane. However, a single injection of ouabain (1 µg/kg) prior HS was unable to prevent the HS-induced membrane depolarization. Chronic administration of ouabain for four days did not change the α1 and α2 Na,K-ATPase protein content, however it partially prevented the HS-induced loss of the Na,K-ATPase electrogenic activity and sarcolemma depolarization. These changes were associated with increased phosphorylation levels of AMP-activated protein kinase (AMPK), its substrate acetyl-CoA carboxylase and p70 protein, accompanied with increased mRNA expression of interleikin-6 (IL-6) and IL-6 receptor. Considering the role of AMPK in regulation of the Na,K-ATPase, we suggest an IL-6/AMPK contribution to prevent the effects of chronic ouabain under skeletal muscle disuse.


1999 ◽  
Vol 276 (2) ◽  
pp. R308-R316 ◽  
Author(s):  
Nathalie Cros ◽  
Jacky Muller ◽  
Sophie Bouju ◽  
Geneviève Piétu ◽  
Chantal Jacquet ◽  
...  

Muscle disuse induces substantial alterations in the highly plastic skeletal muscle tissues, which occur especially in antigravity slow muscles. We differentially screened a muscle cDNA array to identify modifications in gene profile expression induced in slow rat soleus muscle mechanically unloaded by hindlimb suspension as a model for muscle disuse. This study focused on muscle creatine kinase mRNA and protein and glyceraldehyde-3-phosphate dehydrogenase mRNA, which were found to be upregulated in unweighted muscles. These upregulations were analyzed over a 4-wk time course of hindlimb suspension and compared with variations in myosin heavy chain (MHC) isoforms while specifically focusing on type IIx MHC mRNA and protein. The two metabolic marker upregulations clearly preceded IIx MHC contractile protein upregulation. Muscle creatine kinase upregulation was shown to be an excellent, and the earliest, marker of muscle disuse at mRNA and protein levels.


2018 ◽  
Vol 664 ◽  
pp. 1-6 ◽  
Author(s):  
Irina G. Bryndina ◽  
Maria N. Shalagina ◽  
Alexey V. Sekunov ◽  
Andrei L. Zefirov ◽  
Alexey M. Petrov
Keyword(s):  

2003 ◽  
Vol 77 (19) ◽  
pp. 10714-10718 ◽  
Author(s):  
Weiping Peng ◽  
Gail Henderson ◽  
Guey-Chuen Perng ◽  
Anthony B. Nesburn ◽  
Steven L. Wechsler ◽  
...  

ABSTRACT The herpes simplex virus type 1 latency-associated transcript (LAT) inhibits apoptosis. We demonstrate here that LAT influences the accumulation of the Bcl-xL transcript versus the Bcl-xS transcript in Neuro-2A cells. Bcl-xL encodes an antiapoptotic protein, whereas Bcl-xS encodes a proapoptotic protein. Promoting the accumulation of Bcl-xL in neurons may inhibit apoptosis, thus enhancing the latency-reactivation cycle.


2006 ◽  
Vol 21 (2) ◽  
pp. 135-137 ◽  
Author(s):  
Ioannis A. Liappas ◽  
Charalabos C. Papageorgiou ◽  
Andreas D. Rabavilas

AbstractZolpidem is a GABA (A) agonist, which is indicated for the short-term management of insomnia. Recent research provide evidence suggesting that zolpidem produces spatial working memory (WM) deficits and dependence; however, the underlying mechanisms of these effects are unknown. Since the auditory N400 component of event-related potentials (ERPS) is considered as an index of memory use of context processing, the present study focused on N400 waveform of ERPs elicited during a WM task in a case suffering from zolpidem dependence. The patterns of N400 waveform of this case were compared to the patterns obtained from healthy controls. This comparison revealed that zolpidem dependence is accompanied by reduced amplitudes located at posterior brain areas and diffuse prolongation of N400. These findings may indicate that zolpidem dependence manifests alterations with regard to the memory use of context processing, involving or affecting a wide-ranging network of the brain's structures.


1996 ◽  
Vol 81 (6) ◽  
pp. 2540-2546 ◽  
Author(s):  
Robert J. Talmadge ◽  
Roland R. Roy ◽  
V. Reggie Edgerton

Talmadge, Robert J., Roland R. Roy, and V. Reggie Edgerton.Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers. J. Appl. Physiol. 81(6): 2540–2546, 1996.—The effects of 14 days of spaceflight (SF) or hindlimb suspension (HS) (Cosmos 2044) on myosin heavy chain (MHC) isoform content of the rat soleus muscle and single muscle fibers were determined. On the basis of electrophoretic analyses, there was a de novo synthesis of type IIx MHC but no change in either type I or IIa MHC isoform proportions after either SF or HS compared with controls. The percentage of fibers containing only type I MHC decreased by 26 and 23%, and the percentage of fibers with multiple MHCs increased from 6% in controls to 32% in HS and 34% in SF rats. Type IIx MHC was always found in combination with another MHC or combination of MHCs; i.e., no fibers contained type IIx MHC exclusively. These data suggest that the expression of the normal complement of MHC isoforms in the adult rat soleus muscle is dependent, in part, on normal weight bearing and that the absence of weight bearing induces a shift toward type IIx MHC protein expression in the preexisting type I and IIa fibers of the soleus.


2019 ◽  
Vol 498 (1) ◽  
pp. 9-38 ◽  
Author(s):  
Benjamin Sames ◽  
M. Wagreich ◽  
C. P. Conrad ◽  
S. Iqbal

AbstractA review of short-term (<3 myr: c. 100 kyr to 2.4 myr) Cretaceous sea-level fluctuations of several tens of metres indicates recent fundamental progress in understanding the underlying mechanisms for eustasy, both in timing and in correlation. Cretaceous third- and fourth-order hothouse sea-level changes, the sequence-stratigraphic framework, are linked to Milankovitch-type climate cycles, especially the longer-period sequence-building bands of 405 kyr and 1.2 myr. In the absence of continental ice sheets during Cretaceous hothouse phases (e.g. Cenomanian–Turonian), growing evidence indicates groundwater-related sea-level cycles: (1) the existence of Milankovitch-type humid-arid climate oscillations, proven via intense humid weathering records during times of regression and sea-level lowstands; (2) missing or inverse relationships of sea-level and the marine δ18O archives, i.e. the lack of a pronounced positive excursion, cooling signal during sea-level lowstands; and (3) the anti-phase relationship of sea and lake levels, attesting to high groundwater levels and charged continental aquifers during sea-level lowstands. This substantiates the aquifer-eustasy hypothesis. Rates of aquifer-eustatic sea-level change remain hard to decipher; however, reconstructions range from a very conservative minimum estimate of 0.04 mm a−1 (longer time intervals) to 0.7 mm a−1 (shorter, probably asymmetric cycles). Remarkably, aquifer-eustasy is recognized as a significant component for the Anthropocene sea-level budget.


Author(s):  
Sean Paul Kilroe ◽  
Jonathan Fulford ◽  
Sarah Jackman ◽  
Andrew Holwerda ◽  
Annemie Gijsen ◽  
...  

ABSTRACT Background Short-term (&lt;1 wk) muscle disuse lowers daily myofibrillar protein synthesis (MyoPS) rates resulting in muscle mass loss. The understanding of how daily dietary protein intake influences such muscle deconditioning requires further investigation. Objectives To assess the influence of graded dietary protein intakes on daily MyoPS rates and the loss of muscle mass during 3 d of disuse. Methods Thirty-three healthy young men (aged 22 ± 1 y; BMI = 23 ± 1 kg/m2) initially consumed the same standardized diet for 5 d, providing 1.6 g protein/kg body mass/d. Thereafter, participants underwent a 3-d period of unilateral leg immobilization during which they were randomly assigned to 1 of 3 eucaloric diets containing relatively high, low, or no protein (HIGH: 1.6, LOW: 0.5, NO: 0.15 g protein/kg/d; n = 11 per group). One day prior to immobilization participants ingested 400 mL deuterated water (D2O) with 50-mL doses consumed daily thereafter. Prior to and immediately after immobilization upper leg bilateral MRI scans and vastus lateralis muscle biopsies were performed to measure quadriceps muscle volume and daily MyoPS rates, respectively. Results Quadriceps muscle volume of the control legs remained unchanged throughout the experiment (P &gt; 0.05). Immobilization led to 2.3 ± 0.4%, 2.7 ± 0.2%, and 2.0 ± 0.4% decreases in quadriceps muscle volume (P &lt; 0.05) of the immobilized leg in the HIGH, LOW, and NO groups (P &lt; 0.05), respectively, with no significant differences between groups (P &gt; 0.05). D2O ingestion resulted in comparable plasma free [2H]-alanine enrichments during immobilization (∼2.5 mole percentage excess) across groups (P &gt; 0.05). Daily MyoPS rates during immobilization were 30 ± 2% (HIGH), 26 ± 3% (LOW), and 27 ± 2% (NO) lower in the immobilized compared with the control leg, with no significant differences between groups (P &gt; 0.05). Conclusions Three days of muscle disuse induces considerable declines in muscle mass and daily MyoPS rates. However, daily protein intake does not modulate any of these muscle deconditioning responses. Clinical trial registry number: NCT03797781


1998 ◽  
Vol 274 (4) ◽  
pp. R939-R949 ◽  
Author(s):  
J. A. Armour ◽  
K. Collier ◽  
G. Kember ◽  
J. L. Ardell

Analyses of activity generated by neurons in middle cervical or stellate ganglia versus intrinsic cardiac ganglia were performed to determine how neurons in different intrathoracic ganglia, which are involved in cardiac regulation, interact. Discharges of 19% of intrathoracic extracardiac neurons and 32% of intrinsic cardiac neurons were related to cardiodynamics. Epicardial touch increased the activity generated by ∼80% of intrinsic cardiac neurons and ∼60% of extracardiac neurons. Both populations responded similarly to epicardial chemical stimuli. Activity generated by neurons in intrinsic cardiac ganglia demonstrated no consistent short-term relationships to neurons in extracardiac ganglia. Myocardial ischemia influenced extracardiac and intrinsic cardiac neurons similarly. Carotid artery baroreceptors influenced neurons in ipsilateral extracardiac ganglia. After decentralization from the central nervous system, intrinsic cardiac neurons received afferent inputs primarily from cardiac chemosensitive neurites, whereas middle cervical ganglion neurons received afferent inputs primarily from cardiac mechanosensory neurites. It is concluded that the populations of neurons in different intrathoracic ganglia can display differential reflex control of cardiac function. Their redundancy in function and noncoupled behavior minimizes cardiac dependency on a single population of intrathoracic neurons.


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