scholarly journals Plantar Mechanical Stimulation Maintains Slow Myosin Expression in Disused Rat Soleus Muscle via NO-Dependent Signaling

2021 ◽  
Vol 22 (3) ◽  
pp. 1372
Author(s):  
Kristina A. Sharlo ◽  
Inna I. Paramonova ◽  
Irina D. Lvova ◽  
Ekaterina P. Mochalova ◽  
Vitaliy E. Kalashnikov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mechanical Stimulation ◽  
Fiber Type ◽  
Hindlimb Unloading ◽  
No Production ◽  
Mrna Transcription ◽  
Positive Effects ◽  
Myosin I ◽  
Fast Fiber ◽  
Type Shift

It was observed that gravitational unloading during space missions and simulated microgravity in ground-based studies leads to both transformation of slow-twitch muscle fibers into fast-twitch fibers and to the elimination of support afferentation, leading to the “switching-off” of postural muscle motor units electrical activity. In recent years, plantar mechanical stimulation (PMS) has been found to maintain the neuromuscular activity of the hindlimb muscles. Nitric oxide (NO) was shown to be one of the mediators of muscle fiber activity, which can also promote slow-type myosin expression. We hypothesized that applying PMS during rat hindlimb unloading would lead to NO production upregulation and prevention of the unloading-induced slow-to-fast fiber-type shift in rat soleus muscles. To test this hypothesis, Wistar rats were hindlimb suspended and subjected to daily PMS, and one group of PMS-subjected animals was also treated with nitric oxide synthase inhibitor (L-NAME). We discovered that PMS led to sustained NO level in soleus muscles of the suspended animals, and NOS inhibitor administration blocked this effect, as well as the positive effects of PMS on myosin I and IIa mRNA transcription and slow-to-fast fiber-type ratio during rat hindlimb unloading. The results of the study indicate that NOS activity is necessary for the PMS-mediated prevention of slow-to-fast fiber-type shift and myosin I and IIa mRNA transcription decreases during rat hindlimb unloading.

scholarly journals Plantar mechanical stimulation prevents calcineurin-NFATc1 inactivation and slow-to-fast fiber type shift in rat soleus muscle under hindlimb unloading

2019 ◽  
Vol 126 (6) ◽  
pp. 1769-1781 ◽  
Author(s):  
Kristina Sharlo ◽  
Inna Paramonova ◽  
Olga Turtikova ◽  
Sergey Tyganov ◽  
Boris Shenkman
Keyword(s):  
T Cells ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Mechanical Stimulation ◽  
Fiber Type ◽  
Hindlimb Unloading ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Fast Fiber ◽  
Type Shift

The prevailing myosin isoform [myosin heavy chain (MyHC)] in a skeletal muscle determines contractile properties of the muscle. Under actual or simulated microgravity conditions such as human bed rest or rat hindlimb unloading, decrease in expression of MyHC of the slow type [MyHC I(β)] has been observed. It was demonstrated that increasing sensory input by performing plantar mechanical stimulation (PMS) on the soles of the feet results in an increase in neuromuscular activation of the lower limb muscles and may prevent slow-to-fast fiber type shift. The calcineurin-nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway is the main cascade regulating MyHC I(β) expression. The present study was aimed to analyze the states of the calcineurin-NFATc1 signaling cascade under conditions of PMS during rat hindlimb unloading. Male Wistar rats were randomly assigned to vivarium control groups and 1-day unloading (1HS), 3-day unloading (3HS), 1HS+PMS, and 3HS+PMS groups. We found that both 1 day and 3 days of unloading caused decrease in MyHC I(β) mRNA expression and decrease in glycogen synthase kinase-3β phosphorylation (Ser 9) that brought about the kinase activation, and these effects of unloading were prevented by PMS. Three days of unloading also caused increase in expression of calsarcin-2 (myozenin-I), which was found to be the endogenous calcineurin inhibitor. The level of calsarcin-2 expression in the 3HS+PMS group did not differ from the control group. Therefore, we conclude that PMS upregulates the calcineurin-NFATc1 signaling pathway and prevents unloading-induced MyHC I(β) decrease. NEW & NOTEWORTHY It is widely accepted that changes in the myosin phenotype during functional unloading (disuse) are determined by a decreased expression of the myosin heavy chain (MyHC) I(β) gene, and this decrease leads to changes of contractile and fatigue characteristics of soleus muscle. The calcineurin-nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) pathway is one of the most important signaling cascades regulating slow MyHC isoform expression. The present study is the first to show that plantar mechanical stimulation upregulates calcineurin-NFATc1 signaling in soleus muscles of hindlimb-unloaded rats.

scholarly journals Improvement of Contraction Force in Injured Skeletal Muscle after Autologous Mesenchymal Stroma Cell Transplantation Is Accompanied by Slow to Fast Fiber Type Shift

2013 ◽  
Vol 40 (6) ◽  
pp. 2-2 ◽  
Author(s):  
Philipp von Roth ◽  
Tobias Winkler ◽  
Kristina Rechenbach ◽  
Piotr. Radojewski ◽  
Carsten Perka ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Transplantation ◽  
Fiber Type ◽  
Contraction Force ◽  
Stroma Cell ◽  
Fast Fiber ◽  
Mesenchymal Stroma ◽  
Type Shift

scholarly journals Muscle fiber type differences in nitrate and nitrite storage and nitric oxide signaling in rats

2020 ◽  
Author(s):  
Gary M. Long ◽  
Derrick A. Gray ◽  
Ashley D. Troutman ◽  
Amanda Fisher ◽  
Mary Beth Brown ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cgmp Level ◽  
No Production ◽  
Nitric Oxide Signaling ◽  
Slow Twitch ◽  
Fast Twitch

AbstractRecent studies have emphasized the importance of the nitric oxide synthase (NOS)-independent, nitrate (NO3−) → nitrite (NO2−) → nitric oxide (NO) pathway in skeletal muscle. In particular, it has been hypothesized that this pathway is especially active in type II, or fast-twitch, muscle fibers, necessitating greater NO3− and NO2− storage. We therefore measured NO3− and NO2− concentrations in the predominantly fast-twitch vastus lateralis and predominantly slow-twitch soleus muscles of rats. Contrary to the above hypothesis, we found that NO3− and NO2− concentrations were 3.4-fold and 1.8-fold higher, respectively, in the soleus. On the other hand, NO signaling (i.e., cyclic guanosine monophosphate (cGMP) level) was comparable in the two muscles. Although the physiological significance of these observations remains to be determined, we speculate that NO production via the NO3− → NO2− → NO pathway is normally higher in slow-twitch muscles, thus helping compensate for their inherently lower NOS activity.

Sarcomere lesion damage occurs mainly in slow fibers of reloaded rat adductor longus muscles

1998 ◽  
Vol 85 (3) ◽  
pp. 1017-1023 ◽  
Author(s):  
Kalpana Vijayan ◽  
Joyce L. Thompson ◽  
Danny A. Riley
Keyword(s):  
Fiber Type ◽  
Hindlimb Unloading ◽  
Fiber Types ◽  
Hybrid Fiber ◽  
Hybrid Fibers ◽  
Fast Myosin ◽  
Slow Fiber ◽  
Fast Fiber ◽  
Damage Susceptibility ◽  
Adductor Longus

Sarcomere lesions were previously observed with reloading of rat adductor longus muscles after spaceflight and hindlimb unloading (HU). Spaceflown rats displayed more lesioned fibers in the “slow-fiber” region, suggesting a damage-susceptible fiber type. Unloading induces fast myosin expression in some slow fibers, generating hybrid fibers. We examined whether lesion damage differed among slow-, hybrid-, and fast-fiber types in HU-reloaded adductor longus muscles. Temporal HU for 5, 8, 11, 14, and 17 days revealed that hybrid fiber percent, detected by antimyosin immunostaining, peaked at 29 ± 12% by 14 days. A 14-day HU followed by 12–14 h of voluntary reloading was performed to induce lesions. χ2 analysis showed that slow fibers were preferentially damaged, accounting for 92 ± 5% of lesioned fibers; hybrid and fast fibers accounted for 7 ± 4 and <0.5%, respectively. Atrophy did not explain differential lesion damage across fiber types, as slow and hybrid fibers atrophied to a similar extent. Because active myofiber contractions are requisite for lesion formation, selective recruitment of slow fibers most likely explains their damage susceptibility.

Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload

2002 ◽  
Vol 92 (5) ◽  
pp. 2005-2011 ◽  
Author(s):  
Lori W. Smith ◽  
John D. Smith ◽  
David S. Criswell
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Fiber Type ◽  
Surgical Removal ◽  
No Production ◽  
Type I ◽  
Fiber Types ◽  
Muscle Adaptation ◽  
Cross Sectional ◽  
Type Transition

The purpose of this study was to determine the necessity of nitric oxide (NO) for hypertrophy and fiber-type transition in overloaded (OL) skeletal muscle. Endogenous NO production was blocked by administering N G-nitro-l-arginine methyl ester (l-NAME; 0.75 mg/ml; ∼100 mg · kg−1 · day−1) in drinking water. Thirty-eight female Sprague-Dawley rats (∼250 g) were randomly divided into four groups: control-nonoverloaded (Non-OL), control-OL, l-NAME-Non-OL, andl-NAME-OL. Chronic overload of the plantaris was induced bilaterally by surgical removal of the gastrocnemius and soleus. Rats in the Non-OL groups received sham surgeries. l-NAME treatment began 24 h before surgery and continued until the rats were killed 14 days postsurgery. Although OL induced hypertrophy in both control (+76%) and l-NAME (+39%) conditions ( P < 0.05), mean plantaris-to-body mass ratio in thel-NAME-OL group was significantly lower ( P< 0.05) than that in the control-OL group. Microphotometric analysis of histochemically determined fiber types revealed increases in cross-sectional area ( P < 0.05) for all fiber types (types I, IIA, and IIB/X) in the OL plantaris from control rats, whereas l-NAME-OL rats exhibited increases only in type I and IIB/X fibers. SDS-PAGE analysis of myosin heavy chain (MHC) composition in the plantaris indicated a significant ( P< 0.05) OL effect in the control rats. Specifically, the mean proportion of type I MHC increased 6% ( P < 0.05), whereas the proportion of type IIb MHC decreased ∼9% ( P < 0.05). No significant OL effects on MHC profile were observed in the l-NAME rats. These data support a role of NO in overload-induced skeletal muscle hypertrophy and fiber-type transition.

scholarly journals Effects of sarcolipin deletion on skeletal muscle adaptive responses to functional overload and unload

2017 ◽  
Vol 313 (2) ◽  
pp. C154-C161 ◽  
Author(s):  
Val A. Fajardo ◽  
Bradley A. Rietze ◽  
Paige J. Chambers ◽  
Catherine Bellissimo ◽  
Eric Bombardier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Ectopic Expression ◽  
Oxidative Capacity ◽  
Adaptive Responses ◽  
Slow Fiber ◽  
Fast Fiber ◽  
Fiber Number ◽  
Type Shift ◽  
Calcineurin Signaling

Overexpression of sarcolipin (SLN), a regulator of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs), stimulates calcineurin signaling to enhance skeletal muscle oxidative capacity. Some studies have shown that calcineurin may also control skeletal muscle mass and remodeling in response to functional overload and unload stimuli by increasing myofiber size and the proportion of slow fibers. To examine whether SLN might mediate these adaptive responses, we performed soleus and gastrocnemius tenotomy in wild-type (WT) and Sln-null ( Sln−/−) mice and examined the overloaded plantaris and unloaded/tenotomized soleus muscles. In the WT overloaded plantaris, we observed ectopic expression of SLN, myofiber hypertrophy, increased fiber number, and a fast-to-slow fiber type shift, which were associated with increased calcineurin signaling (NFAT dephosphorylation and increased stabilin-2 protein content) and reduced SERCA activity. In the WT tenotomized soleus, we observed a 14-fold increase in SLN protein, myofiber atrophy, decreased fiber number, and a slow-to-fast fiber type shift, which were also associated with increased calcineurin signaling and reduced SERCA activity. Genetic deletion of Sln altered these physiological outcomes, with the overloaded plantaris myofibers failing to grow in size and number, and transition towards the slow fiber type, while the unloaded soleus muscles exhibited greater reductions in fiber size and number, and an accelerated slow-to-fast fiber type shift. In both the Sln−/− overloaded and unloaded muscles, these findings were associated with elevated SERCA activity and blunted calcineurin signaling. Thus, SLN plays an important role in adaptive muscle remodeling potentially through calcineurin stimulation, which could have important implications for other muscle diseases and conditions.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

scholarly journals Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haidy A. Saleh ◽  
Eman Ramdan ◽  
Mohey M. Elmazar ◽  
Hassan M. E. Azzazy ◽  
Anwar Abdelnaser
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Raw 264.7 Cells ◽  
Inos Mrna ◽  
No Production ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Tnf Α ◽  
Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

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