Differential localization of autolyzed calpains 1 and 2 in slow and fast skeletal muscles in the early phase of atrophy

2007 ◽  
Vol 292 (5) ◽  
pp. C1723-C1731 ◽  
Author(s):  
Marianne Vermaelen ◽  
Pascal Sirvent ◽  
Fabrice Raynaud ◽  
Catherine Astier ◽  
Jacques Mercier ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Skeletal Muscles ◽  
Soluble Fraction ◽  
Muscle Disuse ◽  
Short Period ◽  
Slow Type ◽  
Ubiquitin Proteasome ◽  
Rat Soleus Muscle ◽  
Proteolytic Pathways

Calpains have been proposed to be involved in the cytoskeletal remodeling and wasting of skeletal muscle. However, limited data are available about the specific involvement of each calpain in the early stages of muscle atrophy. The aims of this study were to determine whether calpains 1 and 2 are autolyzed after a short period of muscle disuse, and, if so, where in the myofibers the autolyzed products are localized. In the rat soleus muscle, 5 days of immobilization increased autolyzed calpain 1 in the particulate and not the soluble fraction. Conversely, autolyzed calpain 2 was not found in the particulate fraction, whereas it was increased in the soluble fraction after immobilization. In the less atrophied plantaris muscle, no difference was noted between the control and immobilized groups whatever the fraction or calpain. Other proteolytic pathways were also investigated. The ubiquitin-proteasome pathway was activated in both skeletal muscles, and caspase 3 was activated only in the soleus muscle. Taken together, our data suggest that calpains 1 and 2 are involved in atrophy development in slow type muscle exclusively and that they have different regulation and protein targets. Moreover, the activation of proteolytic pathways appears to differ in slow and fast muscles, and the proteolytic mechanisms involved in fast-type muscle atrophy remain unclear.

Calpain and caspase-3 play required roles in immobilization-induced limb muscle atrophy

2013 ◽  
Vol 114 (10) ◽  
pp. 1482-1489 ◽  
Author(s):  
Erin E. Talbert ◽  
Ashley J. Smuder ◽  
Kisuk Min ◽  
Oh Sung Kwon ◽  
Scott K. Powers
Keyword(s):  
Muscle Atrophy ◽  
Caspase 3 ◽  
Respiratory Muscles ◽  
Ubiquitin Proteasome System ◽  
Type I ◽  
Disuse Atrophy ◽  
Limb Muscle ◽  
Disuse Muscle Atrophy ◽  
Ubiquitin Proteasome ◽  
Rat Soleus Muscle

Prolonged skeletal muscle inactivity results in a rapid decrease in fiber size, primarily due to accelerated proteolysis. Although several proteases are known to contribute to disuse muscle atrophy, the ubiquitin proteasome system is often considered the most important proteolytic system during many conditions that promote muscle wasting. Emerging evidence suggests that calpain and caspase-3 may also play key roles in inactivity-induced atrophy of respiratory muscles, but it remains unknown if these proteases are essential for disuse atrophy in limb skeletal muscles. Therefore, we tested the hypothesis that activation of both calpain and caspase-3 is required for locomotor muscle atrophy induced by hindlimb immobilization. Seven days of immobilization (i.e., limb casting) promoted significant atrophy in type I muscle fibers of the rat soleus muscle. Independent pharmacological inhibition of calpain or caspase-3 prevented this casting-induced atrophy. Interestingly, inhibition of calpain activity also prevented caspase-3 activation, and, conversely, inhibition of caspase-3 prevented calpain activation. These findings indicate that a regulatory cross talk exists between these proteases and provide the first evidence that the activation of calpain and caspase-3 is required for inactivity-induced limb muscle atrophy.

scholarly journals Isoform-Specific Na,K-ATPase Alterations Precede Disuse-Induced Atrophy of Rat Soleus Muscle

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Violetta V. Kravtsova ◽  
Vladimir V. Matchkov ◽  
Elena V. Bouzinova ◽  
Alexander N. Vasiliev ◽  
Irina A. Razgovorova ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Muscle Fibers ◽  
Hindlimb Suspension ◽  
Resting Membrane Potential ◽  
Membrane Localization ◽  
Specific Effects ◽  
Contractile Parameters ◽  
Mrna Content ◽  
Rat Soleus Muscle

This study examines the isoform-specific effects of short-term hindlimb suspension (HS) on the Na,K-ATPase in rat soleus muscle. Rats were exposed to 24–72 h of HS and we analyzed the consequences on soleus muscle mass and contractile parameters; excitability and the resting membrane potential (RMP) of muscle fibers; the electrogenic activity, protein, and mRNA content of theα1 andα2 Na,K-ATPase; the functional activity and plasma membrane localization of theα2 Na,K-ATPase. Our results indicate that 24–72 h of HS specifically decreases the electrogenic activity of the Na,K-ATPaseα2 isozyme and the RMP of soleus muscle fibers. This decrease occurs prior to muscle atrophy or any change in contractile parameters. Theα2 mRNA and protein content increased after 24 h of HS and returned to initial levels at 72 h; however, even the increased content was not able to restoreα2 enzyme activity in the disused soleus muscle. There was no change in the membrane localization ofα2 Na,K-ATPase. Theα1 Na,K-ATPase electrogenic activity, protein and mRNA content did not change. Our findings suggest that skeletal muscle use is absolutely required forα2 Na,K-ATPase transport activity and provide the first evidence that Na,K-ATPase alterations precede HS-induced muscle atrophy.

Immobilization-induced activation of key proteolytic systems in skeletal muscles is prevented by a mitochondria-targeted antioxidant

2013 ◽  
Vol 115 (4) ◽  
pp. 529-538 ◽  
Author(s):  
Erin E. Talbert ◽  
Ashley J. Smuder ◽  
Kisuk Min ◽  
Oh Sung Kwon ◽  
Hazel H. Szeto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscles ◽  
Mammalian Target Of Rapamycin ◽  
Skeletal Muscle Atrophy ◽  
Muscle Disuse ◽  
Mitochondrial Ros ◽  
Disuse Muscle Atrophy ◽  
Muscle Fiber Atrophy ◽  
First Time

Long periods of skeletal muscle disuse result in muscle fiber atrophy, and mitochondrial production of reactive oxygen species (ROS) appears to be a required signal for the increase in protein degradation that occurs during disuse muscle atrophy. The experiments detailed here demonstrate for the first time in limb muscle that the inactivity-induced increases in E3 ligase expression and autophagy biomarkers result from increases in mitochondrial ROS emission. Treatment of animals with a mitochondrial-targeted antioxidant also prevented the disuse-induced decrease in anabolic signaling (Akt/mammalian target of rapamycin signaling) that is normally associated with prolonged inactivity in skeletal muscles. Additionally, our results confirm previous findings that treatment with a mitochondrial-targeted antioxidant is sufficient to prevent casting-induced skeletal muscle atrophy, mitochondrial dysfunction, and activation of the proteases calpain and caspase-3. Collectively, these data reveal that inactivity-induced increases in mitochondrial ROS emission play a required role in activation of key proteolytic systems and the downregulation of important anabolic signaling molecules in muscle fibers exposed to prolonged inactivity.

scholarly journals Plantar mechanical stimulation attenuates protein synthesis decline in disused skeletal muscle via modulation of nitric oxide level

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sergey A. Tyganov ◽  
Ekaterina Mochalova ◽  
Svetlana Belova ◽  
Kristina Sharlo ◽  
Sergey Rozhkov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Signaling Pathways ◽  
Soleus Muscle ◽  
Mechanical Stimulation ◽  
No Synthase ◽  
28S Rrna ◽  
Slow Type ◽  
Rat Soleus Muscle ◽  
Type Fiber

AbstractBoth research conducted under microgravity conditions and ground-based space analog studies have shown that air pump-based plantar mechanical stimulation (PMS) of cutaneous mechanoreceptors of the sole of the foot is able to increase neuromuscular activity in the musculature of the lower limbs. This type of stimulation is able to attenuate unloading-induced skeletal muscle atrophy and impaired muscle function. The aim of the present study was to evaluate the effects of PMS on anabolic signaling pathways in rat soleus muscle following 7-day hindlimb suspension (HS) and to elucidate if the effects of PMS on anabolic processes would be NO-dependent. The soles of the feet were stimulated with a frequency of 1-s inflation/1-s deflation with a total of 20 min followed by 10 min rest. This cycle was repeated for 4 h each day. We observed a decrease in the soleus muscle mass after 7-day HS, which was not prevented by PMS. We also observed a decrease in slow-type fiber cross-sectional area (CSA) by 56%, which significantly exceeded a decrease (–22%) in fast-type fiber CSA. PMS prevented a reduction in slow-twitch fiber CSA, but had no effect on fast-twitch fiber CSA. PMS prevented a 63% decrease in protein synthesis after 7-day HS as well as changes in several key anabolic signaling regulators, such as p70S6k, 4E-BP1, GSK3β, eEF-2, p90RSK. PMS also prevented a decrease in the markers of translational capacity (18S and 28S rRNA, c-myc, 45S pre-rRNA). Some effects of PMS on anabolic signaling were altered due to NO-synthase inhibitor (L-NAME) administration. Thus, PMS is able to partially prevent atrophic processes in rat soleus muscle during 7-day HS, affecting slow-type muscle fibers. This effect is mediated by alterations in anabolic signaling pathways and may depend on NO-synthase activity.

scholarly journals Expression of Myosin Heavy Chain Isoforms Along Intrafusal Fibers of Rat Soleus Muscle Spindles After 14 Days of Hindlimb Unloading

2002 ◽  
Vol 50 (11) ◽  
pp. 1543-1553 ◽  
Author(s):  
L. De-Doncker ◽  
F. Picquet ◽  
G. Butler Browne ◽  
M. Falempin
Keyword(s):  
Soleus Muscle ◽  
Muscle Spindles ◽  
Myosin Heavy Chain Isoforms ◽  
Hindlimb Unloading ◽  
Cross Sectional ◽  
Intrafusal Fibers ◽  
Significant Difference ◽  
Slow Type ◽  
Rat Soleus Muscle

Morphological, contractile, histochemical, and electrophoretical characteristics of slow postural muscles are altered after hindlimb unloading (HU). However, very few data on intrafusal fibers (IFs) are available. Our aim was to determine the effects of 14 days of hindlimb unloading on the morphological and immunohistochemical characteristics of IF in rat soleus muscle. Thirty-three control and 32 unloaded spindles were analyzed. The number and distribution of muscle spindles did not appear to be affected after unloading. There was no significant difference in number, cross-sectional area, and histochemical properties of IF between the two groups. However, after unloading, a significant decrease in slow type 1 MHC isoform and a slight increase in slow-tonic MHC expression were observed in the B and C regions of the bag1 fibers. The α-cardiac MHC expression was significantly decreased along the entire length of the bag2 fibers and in the B and C regions of the bag1 fibers. In 12 muscle spindles, the chain fibers expressed the slow type 1 and α-cardiac MHC isoforms over a short distance of the A region, although these isoforms are not normally expressed. The most striking finding of the study was the relative resistance of muscle spindles to perturbation induced by HU.

scholarly journals Inhibition of Akt2 phosphorylation abolishes the calorie restriction-induced improvement in insulin-stimulated glucose uptake by rat soleus muscle

2016 ◽  
Vol 41 (11) ◽  
pp. 1208-1211 ◽  
Author(s):  
Naveen Sharma ◽  
Edward B. Arias ◽  
Gregory D. Cartee
Keyword(s):  
Glucose Uptake ◽  
Calorie Restriction ◽  
Soleus Muscle ◽  
Skeletal Muscles ◽  
Akt Inhibitor ◽  
Rat Soleus Muscle ◽  
Slow Twitch ◽  
Ad Libitum ◽  
Isolated Rat

Calorie restriction (CR; ∼60%–65% of ad libitum consumption) can enhance insulin-stimulated glucose uptake (ISGU) in predominantly slow-twitch skeletal muscles (e.g., soleus) by an incompletely understood mechanism. We used an Akt inhibitor (MK-2206) to eliminate CR’s effect on insulin-stimulated Akt2 phosphorylation in isolated rat soleus muscles. We found long-term CR-enhanced ISGU was abolished by eliminating the CR effect on Akt2 phosphorylation, suggesting the CR-induced benefit on ISGU in the predominantly slow-twitch soleus relies on enhanced Akt2 phosphorylation.

scholarly journals Long-term physical inactivity exacerbates hindlimb unloading-induced muscle atrophy in young rat soleus muscle

2021 ◽  
Author(s):  
Toshinori Yoshihara ◽  
Toshiharu Natsume ◽  
Takamasa Tsuzuki ◽  
Shuo-wen Chang ◽  
Ryo Kakigi ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Physical Inactivity ◽  
Wistar Rats ◽  
Hindlimb Unloading ◽  
Whole Body ◽  
Protein Levels ◽  
Male Wistar Rats ◽  
Rat Soleus Muscle

This study investigated the effects of long-term physical inactivity in adolescent on subsequent hindlimb unloading-induced muscle atrophy in rat soleus muscle. First, 3-week-old male Wistar rats were assigned to an age-matched control (n=6) or a physical inactivity (n=8) group. Rats in the physical inactivity group were housed in narrow cages with approximately half the usual floor space for 8 weeks to limit range of movement. Whole body energy consumption was measured and the blood, organs, femoral bone, and hindlimb muscles were removed. We found that long-term physical inactivity did not affect the metabolic and physiological characteristics of growing rats. Then, fifty-six 3-week-old male Wistar rats were assigned randomly into control (n=28) and physical inactivity (n=28) groups. After 8 weeks, the rats in both groups underwent hindlimb unloading. The soleus muscles were removed before unloading (0-day), and 1, 3, and 7 days after unloading (n=7 for each). Although the soleus muscle weight was significantly decreased after 7 days of hindlimb unloading in both groups, the decrease was drastic in the inactive group. A significant interaction between inactivity and unloading (p<0.01) was observed according to the 4-hydroxynonenal-conjugated protein levels and the histone deacetylase 4 (HDAC4) and NF-kB protein levels. HDAC4 and NF-kB p65 protein levels in the physical inactivity group increased significantly 1 day after hindlimb unloading, along with the mRNA levels of their downstream targets myogenin and muscle RING finger protein 1 (MuRF1). Subsequent protein ubiquitination was upregulated by long-term physical inactivity (p<0.05).

scholarly journals Dietary astaxanthin supplementation attenuates disuse-induced muscle atrophy and myonuclear apoptosis in the rat soleus muscle

2016 ◽  
Vol 67 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Toshinori Yoshihara ◽  
Yuki Yamamoto ◽  
Tsubasa Shibaguchi ◽  
Nobuyuki Miyaji ◽  
Ryo Kakigi ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Rat Soleus Muscle
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