scholarly journals Disuse-induced Preferential Loss of the Giant Protein Titin Depresses Muscle Performance via Abnormal Sarcomeric Organization

2007 ◽  
Vol 131 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Jun Udaka ◽  
Shintaro Ohmori ◽  
Takako Terui ◽  
Iwao Ohtsuki ◽  
Shin'ichi Ishiwata ◽  
...  
Keyword(s):  
Muscle Function ◽  
Molecular Mechanisms ◽  
Force Production ◽  
Muscle Performance ◽  
Skeletal Muscle Atrophy ◽  
Active Force ◽  
Thin Filaments ◽  
Preferential Loss ◽  
Qualitative Performance

Persistent muscle weakness due to disuse-associated skeletal muscle atrophy limits the quality of life for patients with various diseases and individuals who are confined to bed. Fibers from disused muscle exhibit a marked reduction in active force production, which can exacerbate motor function, coupled with the well-known loss of muscle quantity. Despite recent understanding of the signaling pathways leading to the quantity loss, the molecular mechanisms of the depressed qualitative performance still remain elusive. Here we show that long-term disuse causes preferential loss of the giant sarcomere protein titin, associated with changes in physiologic muscle function. Ca2+ sensitivity of active force decreased following 6 wk of hindlimb immobilization in the soleus muscle of the rat, accompanied by a shift in the length-active force relationship to the shorter length side. Our analyses revealed marked changes in the disused sarcomere, with shortening of thick and thin filaments responsible for altered length dependence and expansion of interfilament lattice spacing leading to a reduction in Ca2+ sensitivity. These results provide a novel view that disuse-induced preferential titin loss results in altered muscle function via abnormal sarcomeric organization.

scholarly journals Comparative Biomechanics of Thick Filaments and Thin Filaments with Functional Consequences for Muscle Contraction

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Mark S. Miller ◽  
Bertrand C. W. Tanner ◽  
Lori R. Nyland ◽  
Jim O. Vigoreaux
Keyword(s):  
Mechanical Properties ◽  
Muscle Contraction ◽  
Material Properties ◽  
Muscle Function ◽  
Striated Muscle ◽  
Muscle Performance ◽  
Thin Filaments ◽  
Thick Filaments ◽  
Functional Consequences

The scaffold of striated muscle is predominantly comprised of myosin and actin polymers known as thick filaments and thin filaments, respectively. The roles these filaments play in muscle contraction are well known, but the extent to which variations in filament mechanical properties influence muscle function is not fully understood. Here we review information on the material properties of thick filaments, thin filaments, and their primary constituents; we also discuss ways in which mechanical properties of filaments impact muscle performance.

scholarly journals Relation between skeletal muscle strength and ubiquitin ligase expression in muscle atrophy models in zebrafish larvae (Danio Rerio)

2020 ◽  
Author(s):  
Jiao Liu ◽  
Elisabeth Le ◽  
Matthias Schwartzkopf ◽  
Anders Arner
Keyword(s):  
Skeletal Muscle ◽  
Food Intake ◽  
Muscle Weakness ◽  
Muscle Atrophy ◽  
Ubiquitin Ligase ◽  
Muscle Function ◽  
Skeletal Muscle Atrophy ◽  
Active Force ◽  
Zebrafish Larvae

Abstract Background Skeletal muscle atrophy is often seen in patients with chronic diseases or muscle disuse. Upregulated expression of ubiquitin ligases such as Muscle Ring Finger 1 (MuRF-1) and Muscle Atrophy F-box (MAFbx) has been shown in different immobilization-induced atrophy models, which is believed to be responsible for the enhanced muscle protein proteolysis and thereafter results in muscle weakness. However, currently used immobilization animal models can include artefacts due to difficulty of food intake and stress. Zebrafish larvae 5-6 days after hatching do not require active movement for food intake, and it is possible to assess the muscle function of their trunk muscle. Therefore, we established two muscle atrophy models using zebrafish larvae and aimed to investigate the role of the MuRFs and MAFbx in relation with muscle function.Methods An actin-myosin interaction blocker (BTS) was used to immobilize zebrafish larvae from 3-6 days after hatching; in another series, dexamethasone was fed to larvae from 3-5 days after hatching. Maximal active force of trunk muscles was examined and the distance between adjacent filaments in sarcomeric structure was measured using small angle x-ray diffraction. MuRF and MAFbx expression was determined using real time PCR. Two-way ANOVA was used to analyze the difference between groups.Results We found a significant up-regulation of MuRF-1 and a lower active force generation in dexamethasone treated larvae. However, although the BTS immobilization induced muscle weakness, it was associated with decreased of MuRF-1 to 3 and MAFbx. After 3 days of immobilization, sarcomere became more compressed compared to the controls.Conclusions Two kinds of muscle atrophy models were successfully established in zebrafish larvae. MuRFs and MAFbx was lowered in BTS treated model whereas MuRF-1 was up-regulated in dexamethasone treated model implicating the complex role of ubiquitin ligase in different muscle atrophy models.

scholarly journals Dual Role of Reactive Oxygen Species in Muscle Function: Can Antioxidant Dietary Supplements Counteract Age-Related Sarcopenia?

2019 ◽  
Vol 20 (15) ◽  
pp. 3815 ◽  
Author(s):  
Simona Damiano ◽  
Espedita Muscariello ◽  
Giuliana La Rosa ◽  
Martina Di Maro ◽  
Paolo Mondola ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dietary Supplements ◽  
Muscle Mass ◽  
Muscle Function ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Muscle Performance ◽  
Dual Function ◽  
Antioxidant Supplementation ◽  
Age Related

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and strength. In older people, malnutrition and physical inactivity are often associated with sarcopenia, and, therefore, dietary interventions and exercise must be considered to prevent, delay, or treat it. Among the pathophysiological mechanisms leading to sarcopenia, a key role is played by an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and a decrease in enzymatic antioxidant protection leading to oxidative stress. Many studies have evaluated, in addition to the effects of exercise, the effects of antioxidant dietary supplements in limiting age-related muscle mass and performance, but the data which have been reported are conflicting. In skeletal muscle, ROS/RNS have a dual function: at low levels they increase muscle force and adaptation to exercise, while at high levels they lead to a decline of muscle performance. Controversial results obtained with antioxidant supplementation in older persons could in part reflect the lack of univocal effects of ROS on muscle mass and function. The purpose of this review is to examine the molecular mechanisms underlying the dual effects of ROS in skeletal muscle function and the analysis of literature data on dietary antioxidant supplementation associated with exercise in normal and sarcopenic subjects.

scholarly journals Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

2021 ◽  
Vol 22 (3) ◽  
pp. 1201
Author(s):  
Hsuan Peng ◽  
Kazuhiro Shindo ◽  
Renée R. Donahue ◽  
Ahmed Abdel-Latif
Keyword(s):  
Stem Cell ◽  
Immune Responses ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Clinical Evidence ◽  
Current Knowledge ◽  
Cell Delivery ◽  
Cardiac Cell Therapy ◽  
Stem Cell Treatment

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.

scholarly journals RNAseq Reveals Differential Gene Expression Contributing to Phytophthora nicotianae Adaptation to Partial Resistance in Tobacco

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 656
Author(s):  
Jing Jin ◽  
Rui Shi ◽  
Ramsey Steven Lewis ◽  
Howard David Shew
Keyword(s):  
Partial Resistance ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Effective Means ◽  
Phytophthora Nicotianae ◽  
Economic Losses ◽  
Black Shank ◽  
Differential Gene ◽  
Go Terms

Phytophthora nicotianae is a devastating oomycete plant pathogen with a wide host range. On tobacco, it causes black shank, a disease that can result in severe economic losses. Deployment of host resistance is one of the most effective means of controlling tobacco black shank, but adaptation to complete and partial resistance by P. nicotianae can limit the long-term effectiveness of the resistance. The molecular basis of adaptation to partial resistance is largely unknown. RNAseq was performed on two isolates of P. nicotianae (adapted to either the susceptible tobacco genotype Hicks or the partially resistant genotype K 326 Wz/Wz) to identify differentially expressed genes (DEGs) during their pathogenic interactions with K 326 Wz/Wz and Hicks. Approximately 69% of the up-regulated DEGs were associated with pathogenicity in the K 326 Wz/Wz-adapted isolate when sampled following infection of its adapted host K 326 Wz/Wz. Thirty-one percent of the up-regulated DEGs were associated with pathogenicity in the Hicks-adapted isolate on K 326 Wz/Wz. A broad spectrum of over-represented gene ontology (GO) terms were assigned to down-regulated genes in the Hicks-adapted isolate. In the host, a series of GO terms involved in nuclear biosynthesis processes were assigned to the down-regulated genes in K 326 Wz/Wz inoculated with K 326 Wz/Wz-adapted isolate. This study enhances our understanding of the molecular mechanisms of P. nicotianae adaptation to partial resistance in tobacco by elucidating how the pathogen recruits pathogenicity-associated genes that impact host biological activities.

scholarly journals Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review

2021 ◽  
Vol 22 (10) ◽  
pp. 5145
Author(s):  
Giuseppe Schepisi ◽  
Caterina Gianni ◽  
Sara Bleve ◽  
Silvia De Padova ◽  
Cecilia Menna ◽  
...  
Keyword(s):  
Vitamin D ◽  
Testicular Cancer ◽  
Vitamin D Deficiency ◽  
Molecular Mechanisms ◽  
Hypovitaminosis D ◽  
Young Males ◽  
Report Data ◽  
Testicular Cancer Survivors ◽  
Patients Experience

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications.

scholarly journals Crosstalk between Long-Term Sublethal Oxidative Stress and Detrimental Inflammation as Potential Drivers for Age-Related Retinal Degeneration

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Lara Macchioni ◽  
Davide Chiasserini ◽  
Letizia Mezzasoma ◽  
Magdalena Davidescu ◽  
Pier Luigi Orvietani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Rpe Cells ◽  
Age Related ◽  
Oxidative Insult

Age-related retinal degenerations, including age-related macular degeneration (AMD), are caused by the loss of retinal pigmented epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD, deeply linked to the aging process, also involves oxidative stress and inflammatory responses. However, the molecular mechanisms contributing to the shift from healthy aging to AMD are still poorly understood. Since RPE cells in the retina are chronically exposed to a pro-oxidant microenvironment throughout life, we simulated in vivo conditions by growing ARPE-19 cells in the presence of 10 μM H2O2 for several passages. This long-term oxidative insult induced senescence in ARPE-19 cells without affecting cell proliferation. Global proteomic analysis revealed a dysregulated expression in proteins involved in antioxidant response, mitochondrial homeostasis, and extracellular matrix organization. The analyses of mitochondrial functionality showed increased mitochondrial biogenesis and ATP generation and improved response to oxidative stress. The latter, however, was linked to nuclear factor-κB (NF-κB) rather than nuclear factor erythroid 2–related factor 2 (Nrf2) activation. NF-κB hyperactivation also resulted in increased pro-inflammatory cytokines expression and inflammasome activation. Moreover, in response to additional pro-inflammatory insults, senescent ARPE-19 cells underwent an exaggerated inflammatory reaction. Our results indicate senescence as an important link between chronic oxidative insult and detrimental chronic inflammation, with possible future repercussions for therapeutic interventions.

scholarly journals Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

2021 ◽  
Vol 22 (13) ◽  
pp. 6663
Author(s):  
Maurycy Jankowski ◽  
Mariusz Kaczmarek ◽  
Grzegorz Wąsiatycz ◽  
Claudia Dompe ◽  
Paul Mozdziak ◽  
...  
Keyword(s):  
Stem Cells ◽  
In Vitro Culture ◽  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Marker Genes ◽  
P Value ◽  
Illumina Platform

Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic differentiation of ASCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture and osteogenic differentiation of ASCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ASCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells’ application in regenerative medicine.

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