scholarly journals Muscle Phenotype, Proteolysis, and Atrophy Signaling During Reloading in Mice: Effects of Curcumin on the Gastrocnemius

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 388 ◽  
Author(s):  
Laura Mañas-García ◽  
Nuria Bargalló ◽  
Joaquim Gea ◽  
Esther Barreiro
Keyword(s):  
Protein Synthesis ◽  
Signaling Pathways ◽  
Muscle Function ◽  
Histone Deacetylases ◽  
Troponin I ◽  
Muscle Protein ◽  
Sirtuin 1 ◽  
Hybrid Fibers ◽  
Disuse Muscle Atrophy ◽  
And Function

We hypothesized that curcumin may mitigate muscle protein degradation and loss through attenuation of proteolytic activity in limb muscles of mice exposed to reloading (7dR) following immobilization (7dI). In gastrocnemius of mice (female C57BL/6J, 10 weeks) exposed to recovery following a seven-day period of hindlimb immobilization with/without curcumin treatment, markers of muscle proteolysis (systemic troponin-I), atrophy signaling pathways and histone deacetylases, protein synthesis, and muscle phenotypic characteristics and function were analyzed. In gastrocnemius of reloading mice compared to unloaded, muscle function, structure, sirtuin-1, and protein synthesis improved, while proteolytic and signaling markers (FoxO1/3) declined. In gastrocnemius of unloaded and reloaded mice treated with curcumin, proteolytic and signaling markers (NF-kB p50) decreased and sirtuin-1 activity and hybrid fibers size increased (reloaded muscle), while no significant improvement was seen in muscle function. Treatment with curcumin elicited a rise in sirtuin-1 activity, while attenuating proteolysis in gastrocnemius of mice during reloading following a period of unloading. Curcumin attenuated muscle proteolysis probably via activation of histone deacetylase sirtuin-1, which also led to decreased levels of atrophy signaling pathways. These findings offer an avenue of research in the design of therapeutic strategies in clinical settings of patients exposed to periods of disuse muscle atrophy.

scholarly journals Beneficial Effects of Resveratrol in Mouse Gastrocnemius: A Hint to Muscle Phenotype and Proteolysis

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2436
Author(s):  
Laura Mañas-García ◽  
Charlotte Denhard ◽  
Javier Mateu ◽  
Xavier Duran ◽  
Joaquim Gea ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Muscle Fiber ◽  
Troponin I ◽  
Muscle Protein ◽  
Strength Loss ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Therapeutic Implications ◽  
Resveratrol Treatment ◽  
And Function

We hypothesized that the phenolic compound resveratrol mitigates muscle protein degradation and loss and improves muscle fiber cross-sectional area (CSA) in gastrocnemius of mice exposed to unloading (7dI). In gastrocnemius of mice (female C57BL/6J, 10 weeks) exposed to a seven-day period of hindlimb immobilization with/without resveratrol treatment, markers of muscle proteolysis (tyrosine release, systemic troponin-I), atrophy signaling pathways, and muscle phenotypic features and function were analyzed. In gastrocnemius of unloaded mice treated with resveratrol, body and muscle weight and function were attenuated, whereas muscle proteolysis (tyrosine release), proteolytic and apoptotic markers, atrophy signaling pathways, and myofiber CSA significantly improved. Resveratrol treatment of mice exposed to a seven-day period of unloading prevented body and muscle weight and limb strength loss, while an improvement in muscle proteolysis, proteolytic markers, atrophy signaling pathways, apoptosis, and muscle fiber CSA was observed in the gastrocnemius muscle. These findings may have potential therapeutic implications in the management of disuse muscle atrophy in clinical settings.

Effect of β-hydroxy-β-methylbutyrate (HMB) on muscle strength in older men with prostate cancer (Pca) started on androgen deprivation therapy (ADT): Preliminary results of an open-label, randomized trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 258-258
Author(s):  
Kathryn A. Bylow ◽  
Deepak Kilari ◽  
Matthew John Riese ◽  
John Burfeind ◽  
Melinda Stolley ◽  
...  
Keyword(s):  
Physical Performance ◽  
Muscle Function ◽  
Older Patients ◽  
Muscle Protein ◽  
Older Men ◽  
Fat Free Mass ◽  
Functional Impairments ◽  
Chair Stand ◽  
Preliminary Results ◽  
And Function

258 Background: ADT causes muscle weakness and wasting within 3 months (mo), causing older men on ADT to experience functional impairments and falls. HMB, a leucine metabolite which decreases muscle protein breakdown, improves strength, fat-free mass and function in older patients when given with arginine (A) and glutamine (G). Use of HMB +AG in older men with PCa starting on ADT to improve muscle loss and function has not been reported. Methods: Men age ≥ 60 with Pca starting on ADT were eligible. 42 men to date have been randomized to receive HMB + AG (Juven) twice daily for 3 mo vs no supplement. Physical performance measures using the Short Physical Performance Battery (SPPB) and hand dynamometer measurements were done at baseline and 3 mo. Both of these validated tests predict morbidity and mortality in older patients. Information on primary outcome, body composition, will be reported in the future according to study plan. Interim results are reported here to describe functional geriatric outcomes. Results: 42 men (mean age 70.2) with Pca (42.4% localized, 27.3% biochemical recurrence, 30.3% metastatic) have enrolled to date. Change in SPPB score favored HMB group: 12.6% of HMB vs 23.1% of controls had decline of ≥ 1point (pt) and 56.3% of HMB vs 15.4% of controls had increase of ≥ 1 pt (p = 0.045). The change in timed chair stand portion of SPPB (measures quadriceps strength) trended in favor of HMB group: -1.5 ± 2.9 seconds (sec) for HMB vs +0.4 ± 2.5 sec for controls, p = 0.073. 41.2% of HMB vs 15.4% of controls experienced an improvement in chair stand score. Change in hand grip strength also favored HMB group: 52.9% of HMB vs 84.6% of controls lost strength and 29.4% of HMB vs 0 controls gained strength, p = 0.047. No significant side effects were reported in HMB group. Conclusions: These are preliminary results of an ongoing trial. HMB is well tolerated in men with PCa on ADT. There is a trend in all measures of muscle function in favor of the HMB group. A much higher than expected % of men on HMB experienced improvement in measures of muscle function despite being on ADT. Further studies are ongoing to clarify the role of HMB in older men on ADT. Clinical trial information: NCT01607879.

scholarly journals The effect of young and old ex vivo human serum on cellular protein synthesis and growth in an in vitro model of ageing

2021 ◽  
Author(s):  
Sophie L. Allen ◽  
Ryan N. Marshall ◽  
Sophie J Edwards ◽  
Janet M. Lord ◽  
Gareth G. Lavery ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Human Serum ◽  
Signaling Pathways ◽  
Ex Vivo ◽  
Muscle Protein ◽  
C2c12 Cells ◽  
Muscle Loss ◽  
Older Individuals ◽  
Age Related

In vitro models of muscle ageing are useful for understanding mechanisms of age-related muscle loss and aiding the development of targeted therapies. To investigate mechanisms of age-related muscle loss in vitro utilizing ex vivo human serum, fasted blood samples were obtained from 4 old (72 ± 1 years) and 4 young (26 ± 3 years) men. Older individuals had elevated levels of plasma CRP, IL-6, HOMA-IR, and lower concentric peak torque and work-per-repetition compared with young participants (P < 0.05). C2C12 myotubes were serum and amino acid starved for 1-hour and conditioned with human serum (10%) for 4 or 24-hours. After 4-hours C2C12 cells were treated with 5mM leucine for 30-minutes. Muscle protein synthesis (MPS) was determined through the surface sensing of translation (SUnSET) technique and regulatory signaling pathways measured via Western Blot. Myotube diameter was significantly reduced in myotubes treated with serum from old, in comparison to young donors (84%, P < 0.001). MPS was reduced in myotubes treated with old donor serum, compared to young serum prior to leucine treatment (32%, P < 0.01). MPS and the phosphorylation of Akt, p70S6K and eEF2 were increased in myotubes treated with young serum in response to leucine treatment, with a blunted response identified in cells treated with old serum (P < 0.05). Muscle protein breakdown signaling pathways did not differ between groups. In summary, we show that myotubes conditioned with serum from older individuals had decreased myotube diameter and MPS compared with younger individuals, potentially driven by low-grade systemic inflammation.

scholarly journals The Haplolethal Region at the 16F Gene Cluster of Drosophila melanogaster: Structure and Function

Genetics ◽  
1999 ◽  
Vol 151 (1) ◽  
pp. 163-175 ◽  
Author(s):  
Antonio Prado ◽  
Inmaculada Canal ◽  
Alberto Ferrús
Keyword(s):  
Drosophila Melanogaster ◽  
Troponin I ◽  
Muscle Protein ◽  
Chromosomal Rearrangements ◽  
Regulatory Region ◽  
Lethal Effect ◽  
Functional Expression ◽  
Transcription Unit ◽  
Dominant Lethal ◽  
And Function

Abstract Extensive aneuploid analyses had shown the existence of a few haplolethal (HL) regions and one triplolethal region in the genome of Drosophila melanogaster. Since then, only two haplolethals, 22F1-2 and 16F, have been directly linked to identified genes, dpp and wupA, respectively. However, with the possible exception of dpp, the actual bases for this dosage sensitivity remain unknown. We have generated and characterized dominant-lethal mutations and chromosomal rearrangements in 16F and studied them in relation to the genes in the region. This region extends along 100 kb and includes at least 14 genes. The normal HL function depends on the integrity of a critical 4-kb window of mostly noncoding sequences within the wupA transcription unit that encodes the muscle protein troponin I (TNI). All dominant lethals are breakpoints within that window, which prevent the functional expression of TNI and other adjacent genes in the proximal direction. However, independent mutations in these genes result in recessive lethal phenotypes only. We propose that the HL at 16F represents a long-range cis regulatory region that acts upon a number of functionally related genes whose combined haploidy would yield the dominant-lethal effect.

scholarly journals Effect of fast dietary proteins on muscle protein synthesis rate and muscle strength in ad libitum-fed and energy-restricted old rats

2011 ◽  
Vol 106 (11) ◽  
pp. 1683-1690 ◽  
Author(s):  
Stéphane Walrand ◽  
Aude Zangarelli ◽  
Christelle Guillet ◽  
Jérôme Salles ◽  
Karine Soulier ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Strength ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Old Rats ◽  
And Function ◽  
Muscle Protein Synthesis Rate

Sarcopenia is defined as age-related loss of muscle mass and strength. Energy restriction (ER) delays fibre loss by limiting the accumulated deleterious effects of reactive oxygen species on muscle. However, insufficient protein intake during ER might affect muscle mass and function. We hypothesised that ingestion of fast-digested proteins such as whey protein (WP) improves muscle protein synthesis and muscle strength in aged ER rats. The effect of WP or casein (CAS, slow protein) on muscle mass, protein synthesis and strength was evaluated in 21-month-old rats fed for 5 months either ad libitum (AL) or a 40 % protein and energy-restricted (PER) or 40 % AL-isonitrogenous ER diet. The nitrogen balance was reduced in PER-CAS rats only ( − 48 % v. AL-CAS). WP stimulated muscle protein synthesis rates compared with CAS in all groups (+21,+37 and +34 % in AL, PER and ER conditions, respectively). Muscle strength was higher in ER rats than in AL rats (+23 and +12 % for WP or CAS, respectively). Muscle performance tended to be greater in ER rats fed WP than in ER-CAS rats (P < 0·09). In conclusion, we observed that long-term ER combined with maintained protein intake had a beneficial impact on muscle protein synthesis rate and function during ageing.

scholarly journals The role of dietary protein in optimizing muscle mass, function and health outcomes in older individuals

2012 ◽  
Vol 108 (S2) ◽  
pp. S88-S93 ◽  
Author(s):  
Robert R. Wolfe
Keyword(s):  
Protein Synthesis ◽  
Health Outcomes ◽  
Muscle Mass ◽  
Dietary Protein ◽  
Protein Intake ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Dietary Protein Intake ◽  
Older Individuals ◽  
And Function

The determination of whether increased dietary protein can positively affect health outcomes is hindered by the absence of prospective, randomized trials directly addressing this issue in which all pertinent variables are controlled. Consequently, we can only address the question deductively by considering the support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake. With regard to health outcomes, we have focused on older individuals. Muscle mass and function are progressively lost with aging, so that by the age of 60 many individuals have reached a threshold where function begins to be affected. An association between reduced muscle mass and strength and unfavourable health outcomes is more likely to be revealed in individuals who have significant decrements in muscle mass and strength. In this article support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake is considered. Dietary protein intake, and the resulting increased availability of plasma amino acids, stimulates muscle protein synthesis. If all other variables are controlled, increased muscle protein synthesis leads to improved muscle mass, strength and function over time. Increased muscle mass, strength and function are related to improved health outcomes in older individuals. Since adverse effects of reasonable increases in protein intake above the recommended dietary allowance (RDA) of 0·8 g protein/kg/day have not been reported, it is reasonable to conclude that the optimal protein intake for an older individual is greater than the RDA.

scholarly journals Leucine Improved Growth Performance, Muscle Growth, and Muscle Protein Deposition Through AKT/TOR and AKT/FOXO3a Signaling Pathways in Hybrid Catfish Pelteobagrus vachelli × Leiocassis longirostris

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 327 ◽  
Author(s):  
Ye Zhao ◽  
Jin-Yang Li ◽  
Qin Jiang ◽  
Xiao-Qiu Zhou ◽  
Lin Feng ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Signaling Pathways ◽  
Muscle Protein ◽  
Muscle Growth ◽  
Protein Deposition ◽  
Factor I ◽  
Hybrid Catfish ◽  
Leiocassis Longirostris ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

(1) Background: l-leucine (Leu) plays a positive role in regulating protein turnover in skeletal muscle in mammal. However, the molecular mechanism for the effects of Leu on muscle growth and protein deposition is not clearly demonstrated in fish. This study investigated the effects of dietary Leu on growth performance and muscle growth, protein synthesis, and degradation-related signaling pathways of hybrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂). (2) Methods: A total of 630 hybrid catfish (23.19 ± 0.20 g) were fed 6 different experimental diets containing graded levels of Leu at 10.0 (control), 15.0, 20.0, 25.0, 30.0, 35.0, and 40.0 g Leu kg-1 for 8 weeks. (3) Results: Results showed that dietary Leu increased percent weight gain (PWG), specific growth rate (SGR), FI (feed intake), feed efficiency (FE), protein efficiency ratio (PER), muscle fibers diameter, and muscle fibers density; up-regulated insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), proliferating cell nuclear antigen (PCNA), myogenic regulation factors (MyoD, Myf5, MyoG, and Mrf4), and MyHC mRNA levels; increased muscle protein synthesis via regulating the AKT/TOR signaling pathway; and attenuated protein degradation via regulating the AKT/FOXO3a signaling pathway. (4) Conclusions: These results suggest that Leu has potential role to improve muscle growth and protein deposition in fish, which might be due to the regulation of IGF mRNA expression, muscle growth related gene, and protein synthesis and degradation-related signaling pathways. Based on the broken-line model, the Leu requirement of hybrid catfish (23.19-54.55 g) for PWG was estimated to be 28.10 g kg-1 of the diet (73.04 g kg-1 of dietary protein). These results will improve our understanding of the mechanisms responsible for muscle growth and protein deposition effects of Leu in fish.

scholarly journals Impact of dairy protein during limb immobilization and recovery on muscle size and protein synthesis; a randomized controlled trial

2018 ◽  
Vol 124 (3) ◽  
pp. 717-728 ◽  
Author(s):  
Cameron J. Mitchell ◽  
Randall F. D’Souza ◽  
Sarah M. Mitchell ◽  
Vandre C. Figueiredo ◽  
Benjamin F. Miller ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Controlled Trial ◽  
Protein Supplementation ◽  
Muscle Size ◽  
Thigh Muscle ◽  
Muscle Disuse ◽  
And Function ◽  
Dairy Protein

Muscle disuse results in the loss of muscular strength and size, due to an imbalance between protein synthesis (MPS) and breakdown (MPB). Protein ingestion stimulates MPS, although it is not established if protein is able to attenuate muscle loss with immobilization (IM) or influence the recovery consisting of ambulatory movement followed by resistance training (RT). Thirty men (49.9 ± 0.6 yr) underwent 14 days of unilateral leg IM, 14 days of ambulatory recovery (AR), and a further six RT sessions over 14 days. Participants were randomized to consume an additional 20 g of dairy protein or placebo with a meal during the intervention. Isometric knee extension strength was reduced following IM (−24.7 ± 2.7%), partially recovered with AR (−8.6 ± 2.6%), and fully recovered after RT (−0.6 ± 3.4%), with no effect of supplementation. Thigh muscle cross-sectional area decreased with IM (−4.1 ± 0.5%), partially recovered with AR (−2.1 ± 0.5%), and increased above baseline with RT (+2.2 ± 0.5%), with no treatment effect. Myofibrillar MPS, measured using deuterated water, was unaltered by IM, with no effect of protein. During AR, MPS was increased only with protein supplementation. Protein supplementation did not attenuate the loss of muscle size and function with disuse or potentiate recovery but enhanced myofibrillar MPS during AR. NEW & NOTEWORTHY Twenty grams of daily protein supplementation does not attenuate the loss of muscle size and function induced by 2 wk of muscle disuse or potentiate recovery in middle-age men. Average mitochondrial but not myofibrillar muscle protein synthesis was attenuated during immobilization with no effect of supplementation. Protein supplementation increased myofibrillar protein synthesis during a 2-wk period of ambulatory recovery following disuse but without group differences in phenotype recovery.

Sign in / Sign up

Export Citation Format

Share Document