scholarly journals The role of the recently discovered E3 ubiquitin ligase UBR5 in skeletal muscle mass regulation

2019 ◽  
Vol 597 (16) ◽  
pp. 4133-4135
Author(s):  
Valentin Dablainville ◽  
Anthony M. J. Sanchez
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Ubiquitin Ligase ◽  
Skeletal Muscle Mass ◽  
E3 Ubiquitin Ligase

scholarly journals Knockdown of the E3 ubiquitin ligase UBR5 and its role in skeletal muscle anabolism

2021 ◽  
Vol 320 (1) ◽  
pp. C45-C56
Author(s):  
David C. Hughes ◽  
Daniel C. Turner ◽  
Leslie M. Baehr ◽  
Robert A. Seaborne ◽  
Mark Viggars ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Ubiquitin Ligase ◽  
Fluorescent Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Tibialis Anterior Muscle ◽  
E3 Ubiquitin Ligase ◽  
Skeletal Muscle Atrophy ◽  
The Impact

UBR5 is an E3 ubiquitin ligase positively associated with anabolism, hypertrophy, and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5’s role in the regulation of skeletal muscle mass remain unknown. The present study aimed to elucidate these mechanisms by silencing the UBR5 gene in vivo. To achieve this aim, we electroporated a UBR5-RNAi plasmid into mouse tibialis anterior muscle to investigate the impact of reduced UBR5 on anabolic signaling MEK/ERK/p90RSK and Akt/GSK3β/p70S6K/4E-BP1/rpS6 pathways. Seven days after UBR5 RNAi electroporation, although reductions in overall muscle mass were not detected, the mean cross-sectional area (CSA) of green fluorescent protein (GFP)-positive fibers were reduced (−9.5%) and the number of large fibers were lower versus the control. Importantly, UBR5-RNAi significantly reduced total RNA, muscle protein synthesis, ERK1/2, Akt, and GSK3β activity. Although p90RSK phosphorylation significantly increased, total p90RSK protein levels demonstrated a 45% reduction with UBR5-RNAi. Finally, these early events after 7 days of UBR5 knockdown culminated in significant reductions in muscle mass (−4.6%) and larger reductions in fiber CSA (−18.5%) after 30 days. This was associated with increased levels of phosphatase PP2Ac and inappropriate chronic elevation of p70S6K and rpS6 between 7 and 30 days, as well as corresponding reductions in eIF4e. This study demonstrates that UBR5 plays an important role in anabolism/hypertrophy, whereby knockdown of UBR5 culminates in skeletal muscle atrophy.

scholarly journals Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

2020 ◽  
Vol 21 (5) ◽  
pp. 1628 ◽  
Author(s):  
Keisuke Hitachi ◽  
Masashi Nakatani ◽  
Shiori Funasaki ◽  
Ikumi Hijikata ◽  
Mizuki Maekawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Muscle Size ◽  
Skeletal Muscle Atrophy ◽  
Myostatin Gene ◽  
Expression Levels ◽  
Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

scholarly journals Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake

Aging Cell ◽  
2015 ◽  
Vol 14 (4) ◽  
pp. 511-523 ◽  
Author(s):  
Adam P. Sharples ◽  
David C. Hughes ◽  
Colleen S. Deane ◽  
Amarjit Saini ◽  
Colin Selman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Dietary Restriction ◽  
Protein Intake ◽  
Skeletal Muscle Mass

scholarly journals Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer

2018 ◽  
Author(s):  
Hiroshi Fukushima ◽  
Kosuke Takemura ◽  
Hiroaki Suzuki ◽  
Fumitaka Koga
Keyword(s):  
Skeletal Muscle ◽  
Bladder Cancer ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Prognostic Biomarker ◽  
Inflammatory Diseases ◽  
Poor Nutritional Status ◽  
Lack Of Exercise ◽  
Worse Prognosis

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.

scholarly journals WITHDRAWN (By Publisher): Letter to the Editor: Protective Role of Skeletal Muscle Mass Against Progression From Metabolically Healthy to Unhealthy Phenotype

2019 ◽  
Vol 104 (8) ◽  
pp. W1-W3
Author(s):  
Jean-Christophe Lagacé ◽  
Dominic Tremblay ◽  
Jasmine Paquin ◽  
Alexis Marcotte-Chénard ◽  
Eléonor Riesco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Protective Role ◽  
Letter To The Editor ◽  
Metabolically Healthy

Study investigating the role of skeletal muscle mass estimation in metastatic spinal cord compression

2015 ◽  
Vol 24 (10) ◽  
pp. 2150-2155 ◽  
Author(s):  
H. Gakhar ◽  
A. Dhillon ◽  
J. Blackwell ◽  
K. Hussain ◽  
R. Bommireddy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Spinal Cord ◽  
Muscle Mass ◽  
Spinal Cord Compression ◽  
Skeletal Muscle Mass ◽  
Cord Compression ◽  
Metastatic Spinal Cord Compression ◽  
Mass Estimation

scholarly journals FRI0384 BODY COMPOSITION AS A MEDIATOR IN THE RELATIONSHIP BETWEEN PHYSICAL ACTIVITY AND PHYSICAL FUNCTION IN LOWER-LIMB OSTEOARTHRITIS: RESULTS FROM THE KHOALA COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 789.1-790 ◽  
Author(s):  
M. Wieczorek ◽  
C. Rotonda ◽  
J. Sellam ◽  
F. Guillemin ◽  
A. C. Rat
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Fat Mass ◽  
Skeletal Muscle Mass ◽  
Weight Bearing ◽  
Fat Mass Index ◽  
Mediating Role ◽  
Skeletal Muscle Mass Index

Background:Many trials investigated the beneficial effect of physical activity (PA) on physical function (PF) in people with osteoarthritis (OA), but factors involved in this relationship are poorly understood. Considering the link between OA and obesity and obesity-related disorders, body composition (BC) could be one of these factors.Objectives:To examine the relationships between baseline components of PA and 5-year PF scores, considering BC variables measured at 3 years as potential mediators in theses associations (Figure).Methods:We used data from the KHOALA cohort, a French population-based multicenter cohort of 878 patients with symptomatic knee and/or hip OA, aged between 40 and 75 years old. Baseline PA intensity (Metabolic Equivalent of Task, MET), frequency (times/week), duration (hours/week) and type (weight-bearing or not) were assessed by the Modifiable Activity Questionnaire. PF was measured with the WOMAC questionnaire at 5 years (higher scores = greater functional limitations).Skeletal muscle mass (grams) and fat mass (grams) were measured by dual X-ray absorptiometry (DXA) in 358 patients at 3 years. Fat mass index (kg/m2), appendicular fat mass (kg), % of fat mass, lean mass index (kg/m2), appendicular muscle mass (kg), skeletal muscle mass index (kg/m2or %) were calculated based on DXA data. Sarcopenia was defined according to the FNIH Sarcopenia Project recommendations.A causal mediation analysis was used to highlight the mediating role of BC variables. Bivariate analyses (multiple linear and logistic regressions) were performed to select the variables of interest. Separate generalized linear models were used to describe the relationships between PA components, PF and selected BC variables. Unadjusted and adjusted for baseline confounders (age, gender, number of comorbidities, disease duration, mental health and vitality scores) models were ran.Results:A 1-MET increase in baseline PA intensity was significantly associated with an improvement in PF at 5 years (-3 points). Weight-bearing PA was also significantly associated with better PF scores (-5 points).A 1-MET-increase in PA intensity at baseline was associated with a subsequent decrease at 3 years in fat mass index (-0.86 k/m2), an increase in skeletal muscle mass index (≥ 6%), and a decrease in % of fat mass (-2%). Non-weight-bearing PA was significantly associated with a decrease in fat mass index (-2.5 kg/m2).A 1-point increase in PF score was associated with a reduction in skeletal muscle mass index (calculated from body mass index, -0.3%) and an increase in skeletal muscle mass index (calculated from height, +3 kg/m2). The presence of sarcopenia was significantly associated with a degradation of PF (+7 points).Crude analyses indicated that 20.4% of the effect of baseline PA intensity on PF scores at 5 years was mediated by skeletal muscle mass index (calculated from height), 23.2% by fat mass index and 26.6% by % of fat mass. Similarly, 19.3% of the effect of baseline PA type on PF scores at 5 years was mediated by fat mass index and 15.1% by % of fat mass. After adjustment, we found no longer evidence of a mediating role of BC variables in these associations.Conclusion:We found significant associations between a 1-MET increase in PA intensity, weight-bearing PA at baseline and improvement in PF at 5 years, without any mediating role of BC variables. Further studies are needed to better understand the factors involved in these associations, especially psychosocial variables.Disclosure of Interests:Maud Wieczorek: None declared, Christine Rotonda: None declared, Jérémie SELLAM: None declared, Francis Guillemin Grant/research support from: Francis Guillemin received a grant from Expanscience paid to his institution., Anne-Christine Rat: None declared

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