scholarly journals Polyphenol-Enriched Plum Extract Enhances Myotubule Formation and Anabolism while Attenuating Colon Cancer-induced Cellular Damage in C2C12 Cells

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1077 ◽  
Author(s):  
Faten A. Alsolmei ◽  
Haiwen Li ◽  
Suzette L. Pereira ◽  
Padmavathy Krishnan ◽  
Paul W. Johns ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Cancer Cells ◽  
Total Protein ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
C2c12 Cells ◽  
Cellular Damage ◽  
Myoblast Differentiation ◽  
Colon 26

Preventing muscle wasting in certain chronic diseases including cancer is an ongoing challenge. Studies have shown that polyphenols derived from fruits and vegetables shows promise in reducing muscle loss in cellular and animal models of muscle wasting. We hypothesized that polyphenols derived from plums (Prunus domestica) could have anabolic and anti-catabolic benefits on skeletal muscle. The effects of a polyphenol-enriched plum extract (PE60) were evaluated in vitro on C2C12 and Colon-26 cancer cells. Data were analyzed using a one-way ANOVA and we found that treatment of myocytes with plum extract increased the cell size by ~3-fold (p < 0.05) and stimulated myoblast differentiation by ~2-fold (p < 0.05). Plum extract induced total protein synthesis by ~50% (p < 0.05), reduced serum deprivation-induced total protein degradation by ~30% (p < 0.05), and increased expression of Insulin-Like Growth Factor-1 (IGF-1) by ~2-fold (p < 0.05). Plum extract also reduced tumor necrosis factor α (TNFα)-induced nuclear factor κB (NFκB) activation by 80% (p < 0.05) in A549/NF-κB-luc cells. In addition, plum extract inhibited the growth of Colon-26 cancer cells, and attenuated cytotoxicity in C2C12 myoblasts induced by soluble factors released from Colon-26 cells. In conclusion, our data suggests that plum extract may have pluripotent health benefits on muscle, due to its demonstrated ability to promote myogenesis, stimulate muscle protein synthesis, and inhibit protein degradation. It also appears to protect muscle cell from tumor-induced cytotoxicity.

scholarly journals Polyphenol-Enriched Plum Extract Enhances Myotubule Formation and Anabolism while Attenuating Colon Cancer-induced Cellular Damage in C2C12 Cells

2019 ◽  
Author(s):  
Faten A. Alsolmei ◽  
Haiwen Li ◽  
Suzette L. Pereira ◽  
Padmavathy Krishnan ◽  
Paul W. Johns ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Cancer Cells ◽  
Total Protein ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
C2c12 Cells ◽  
Cellular Damage ◽  
Myoblast Differentiation ◽  
Colon 26

Preventing muscle wasting in certain chronic diseases including cancer is an ongoing challenge. Studies have shown that polyphenols derived from fruits and vegetables show promise in reducing muscle loss in cellular and animal models of muscle wasting. We hypothesized that polyphenols derived from plum (Prunus domestica) could have anabolic and anti-catabolic benefits on skeletal muscle. The effects of a polyphenol-enriched plum extract (PE60) were evaluated in vitro on C2C12 and Colon-26 cancer cells. Treatment of myocytes with plum extract increased the cell size by ~3-fold (p&lt;0.05) and stimulated myoblast differentiation by ~2-fold (p&lt;0.05). Plum extract induced total protein synthesis by ~50% (p&lt;0.05), reduced serum deprivation- induced total protein degradation by ~30% (P&lt;0.05), and increased expression of IGF-1 by ~2-fold (p&lt;0.05). Plum extract also reduced TNF&alpha;-induced NFkB activation by 80% (p&lt;0.05) in A549/NFkB-luc cells. In addition, plum extract inhibited growth of Colon-26 cancer cells, and attenuated cytotoxicity in C2C12 myoblasts induced by soluble factors released from Colon-26 cells. In conclusion, our data suggest that plum extract may have pluripotent health benefits on muscle based on its demonstrated ability to promote myogenesis, stimulate muscle protein synthesis, and inhibit protein degradation. It also appears to protect muscle cell from tumor-induced cytotoxicity.

scholarly journals Effect of corticosterone treatment on muscle protein turnover in adrenalectomized rats and diabetic rats maintained on insulin

1982 ◽  
Vol 204 (3) ◽  
pp. 663-672 ◽  
Author(s):  
Bhanu R. Odedra ◽  
David J. Millward
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Diabetic Rats ◽  
Constant Infusion ◽  
Degradation Rates ◽  
Adrenalectomized Rats

The effect of corticosterone on protein turnover in skeletal muscle was investigated in growing rats. Protein synthesis was measured in vivo by the constant infusion of [14C]tyrosine. The extent to which any effect of corticosterone is modulated by the hyperinsulinaemia induced by steroid treatment was examined by giving the hormone not only to adrenalectomized rats but also to streptozotocin-induced diabetic rats maintained throughout the treatment period on two dosages of insulin by an implanted osmotic minipump. Approximate rates of protein degradation were also estimated in some cases as the difference between synthesis and net change in muscle protein mass. Measurements were also made of free 3-methylhistidine concentration in muscle and plasma. At 10mg of corticosterone/100g body wt. per day, growth stopped and muscle wasting occurred, whereas at 5 mg of corticosterone/100g body wt. per day no net loss of protein occurred. However, this low dose did induce muscle wasting when insulin concentration was regulated by a dose of 1.2 units/day. Protein synthesis was markedly depressed in all treated groups, the depression in the insulin-maintained rats being marginally more than in the hyperinsulinaemic adrenalectomized rats. The oxidative soleus muscle appeared to be less susceptible to the effect of the corticosterone than was the more glycolytic plantaris or gastrocnemius muscle. Any effect of the corticosterone on protein degradation was much less than its effects on protein synthesis. Where increases in the degradation rates appeared to occur in the rats treated with 10mg of corticosterone/100g body wt. per day, the increases were less than 20%. The free intracellular 3-methylhistidine concentrations were doubled in all groups treated with 5 mg of corticosterone/100g body wt. per day and increased 5-fold in the adrenalectomized rats treated with 10mg of corticosterone/100g body wt. per day, with no change in plasma concentration in any of the groups. It is therefore concluded that: (a) the suppression of protein synthesis is the main effect of glucocorticoids in muscle; (b) marked increases in insulin afford only minor protection against this effect; (c) stimulation of protein degradation may occur, but to a much lesser extent.

scholarly journals The Leucine Catabolite and Dietary Supplement β-Hydroxy-β-Methyl Butyrate (HMB) as an Epigenetic Regulator in Muscle Progenitor Cells

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 512
Author(s):  
Virve Cavallucci ◽  
Giovambattista Pani
Keyword(s):  
Histone Acetylation ◽  
Dietary Supplement ◽  
Hdac Inhibitor ◽  
Muscle Wasting ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Epigenetic Mark ◽  
Epigenetic Regulator ◽  
Methyl Butyrate

β-Hydroxy-β-Methyl Butyrate (HMB) is a natural catabolite of leucine deemed to play a role in amino acid signaling and the maintenance of lean muscle mass. Accordingly, HMB is used as a dietary supplement by sportsmen and has shown some clinical effectiveness in preventing muscle wasting in cancer and chronic lung disease, as well as in age-dependent sarcopenia. However, the molecular cascades underlying these beneficial effects are largely unknown. HMB bears a significant structural similarity with Butyrate and β-Hydroxybutyrate (βHB), two compounds recognized for important epigenetic and histone-marking activities in multiple cell types including muscle cells. We asked whether similar chromatin-modifying actions could be assigned to HMB as well. Exposure of murine C2C12 myoblasts to millimolar concentrations of HMB led to an increase in global histone acetylation, as monitored by anti-acetylated lysine immunoblotting, while preventing myotube differentiation. In these effects, HMB resembled, although with less potency, the histone deacetylase (HDAC) inhibitor Sodium Butyrate. However, initial studies did not confirm a direct inhibitory effect of HMB on HDACs in vitro. β-Hydroxybutyrate, a ketone body produced by the liver during starvation or intense exercise, has a modest effect on histone acetylation of C2C12 cells or in vitro HDAC inhibitor activities, and, unlike Butyrate and HMB, did not interfere with myotube formation in a myoblast differentiation assay. Instead, βHB dramatically increased lysine β-hydroxybutyrylation (Kbhb) of histone tails, an epigenetic mark associated with fasting responses and muscle catabolic states. However, when C2C12 cells were exposed to βHB in the presence of equimolar HMB this chromatin modification was drastically reduced, pointing to a role for HMB in attenuating ketosis-associated muscle wasting. In conclusion, while their mechanistic underpinnings remain to be clarified, these preliminary observations highlight novel and potentially important activities of HMB as an epigenetic regulator and βHB antagonist in muscle precursor cells, to be further explored in their biomedical implications.

Pentoxifylline decreases body weight loss and muscle protein wasting characteristics of sepsis

1993 ◽  
Vol 265 (4) ◽  
pp. E660-E666 ◽  
Author(s):  
D. Breuille ◽  
M. C. Farge ◽  
F. Rose ◽  
M. Arnal ◽  
D. Attaix ◽  
...  
Keyword(s):  
Body Weight ◽  
Protein Synthesis ◽  
Acute Phase ◽  
Protein Metabolism ◽  
Muscle Wasting ◽  
Acute Phase Protein ◽  
Muscle Protein ◽  
Liver Protein ◽  
Phase Protein

Sepsis induces metabolic disorders that include loss of body weight, muscle wasting, and acute-phase protein synthesis in liver. Cytokines are generally recognized as active mediators of these disorders, and the implication of tumor necrosis factor (TNF) has been frequently discussed in the recent past. However, the identity of the active agent in alterations of protein metabolism is still controversial. To improve our understanding of the role of cytokines in mediating muscle wasting observed in sepsis, we investigated muscle and liver protein metabolism in the following three groups of rats: infected control rats (INF-C); infected rats pretreated with pentoxifylline (PTX-INF), which is a potent inhibitor of TNF secretion; and pair-fed rats for the PTX-INF group pretreated with pentoxifylline. Pentoxifylline nearly completely suppressed TNF secretion but did not influence the transient fall in rectal temperature, the decreased hematocrit, and the increased liver protein mass and synthesis observed in INF-C rats. Pentoxifylline decreased the anorexia, the loss of body weight and muscle protein observed in INF-C animals, and partially prevented the decrease in muscle protein synthesis induced by infection. The overall data indicate that pentoxifylline is an effective agent in mitigating the characteristic muscle protein wasting induced by sepsis and confirm the limited role of TNF in the mediation of the acute-phase protein synthesis. Our results suggest a probable implication of TNF in the regulation of protein balance in muscle but do not allow discarding possible implication of other mediators that would be inhibited by pentoxifylline.

Quercetin enhances the antitumor effect of trichostatin A and suppresses muscle wasting in tumor-bearing mice

2018 ◽  
Vol 9 (2) ◽  
pp. 871-879 ◽  
Author(s):  
Shu-Ting Chan ◽  
Cheng-Hung Chuang ◽  
Yi-Chin Lin ◽  
Jiunn-Wang Liao ◽  
Chong-Kuei Lii ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Antitumor Effect ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Trichostatin A ◽  
Tumor Bearing ◽  
Muscle Protein Degradation

Quercetin prevents TSA-induced muscle wasting by down-regulating FOXO1 mediated muscle protein degradation.

Total and net muscle protein breakdown in infection determined by amino acid effluxes

1990 ◽  
Vol 258 (5) ◽  
pp. E856-E863 ◽  
Author(s):  
J. Sjolin ◽  
H. Stjernstrom ◽  
G. Friman ◽  
J. Larsson ◽  
J. Wahren
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Urinary Excretion ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Human Infection ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Skeletal Muscle Protein ◽  
Mild Disease

The present investigation was undertaken to study whether, in human infection of varying severity, peripheral 3-methylhistidine efflux and urinary excretion are associated with net protein degradation and to estimate the protein synthesis rate from the combined effluxes of 3-methylhistidine, tyrosine, and phenylalanine. Quadruplicate femoral arteriovenous differences of 3-methylhistidine, tyrosine, and phenylalanine were multiplied by leg plasma flow in 15 infected patients. Leg effluxes for 3-methylhistidine, tyrosine, and phenylalanine were -0.074 +/- 0.011, -2.57 +/- 0.43, and -3.17 +/- 0.44 mumol/min, respectively. There was a significant linear relationship (P less than 0.01) between the effluxes of tyrosine and phenylalanine and the efflux and urinary excretion of 3-methylhistidine. A significant release of tyrosine and phenylalanine was observed in patients studied at the 3-methylhistidine level seen in normal healthy subjects. It is concluded that in infection 1) there is an increased breakdown of skeletal muscle protein and a reduced rate of protein synthesis, with the latter being relatively more important in patients with mild disease; and 2) urinary 3-methylhistidine excretion is associated with net skeletal muscle protein degradation for the patient group studied.

scholarly journals Comparison of protein synthesis and degradation in incubated and perfused muscle

1983 ◽  
Vol 212 (3) ◽  
pp. 649-653 ◽  
Author(s):  
A S Clark ◽  
W E Mitch
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Insulin Treatment ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Protein Degradation ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Rates of muscle protein synthesis and degradation measured in the perfused hindquarter were compared with those in incubated epitrochlearis muscles. With fed or starved mature rats, results without insulin treatment were identical. With insulin treatment, protein synthesis in perfused hindquarters was greater, though protein degradation was the same. Thus rates of muscle protein degradation estimated by these two methods in vitro correspond closely.

scholarly journals Anabolic signaling and protein deposition are enhanced by intermittent compared with continuous feeding in skeletal muscle of neonates

2012 ◽  
Vol 302 (6) ◽  
pp. E674-E686 ◽  
Author(s):  
Samer W. El-Kadi ◽  
Agus Suryawan ◽  
Maria C. Gazzaneo ◽  
Neeraj Srivastava ◽  
Renán A. Orellana ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Whole Body ◽  
Signaling Proteins ◽  
Protein Deposition ◽  
Intermittent Bolus ◽  
Continuous Feeding

Orogastric tube feeding is indicated for neonates with impaired ability to ingest and can be administered by intermittent bolus or continuous schedule. Our aim was to determine whether feeding modalities affect muscle protein deposition and to identify mechanisms involved. Neonatal pigs were overnight fasted (FAS) or fed the same amount of food continuously (CON) or intermittently (INT; 7 × 4 h meals) for 29 h. For 8 h, between hours 20 and 28, pigs were infused with [2H5]phenylalanine and [2H2]tyrosine, and amino acid (AA) net balances were measured across the hindquarters. Insulin, branched-chain AA, phenylalanine, and tyrosine arterial concentrations and whole body phenylalanine and tyrosine fluxes were greater for INT after the meal than for CON or FAS. The activation of signaling proteins leading to initiation of mRNA translation, including eukaryotic initiation factor (eIF)4E·eIF4G complex formation in muscle, was enhanced by INT compared with CON feeding or FAS. Signaling proteins of protein degradation were not affected by feeding modalities except for microtubule-associated protein light chain 3-II, which was highest in the FAS. Across the hindquarters, AA net removal increased for INT but not for CON or FAS, with protein deposition greater for INT. This was because protein synthesis increased following feeding for INT but remained unchanged for CON and FAS, whereas there was no change in protein degradation across any dietary treatment. These results suggest that muscle protein accretion in neonates is enhanced with intermittent bolus to a greater extent than continuous feeding, mainly by increased protein synthesis.

Leucine-stimulated mTOR signaling is partly attenuated in skeletal muscle of chronically uremic rats

2011 ◽  
Vol 301 (5) ◽  
pp. E873-E881 ◽  
Author(s):  
Yu Chen ◽  
Sumita Sood ◽  
Kevin McIntire ◽  
Richard Roth ◽  
Ralph Rabkin
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Signaling Pathway ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Exercise Induced ◽  
Rps6 Phosphorylation

The branched-chain amino acid leucine stimulates muscle protein synthesis in part by directly activating the mTOR signaling pathway. Furthermore, leucine, if given in conjunction with resistance exercise, enhances the exercise-induced mTOR signaling and protein synthesis. Here we tested whether leucine can activate the mTOR anabolic signaling pathway in uremia and whether it can enhance work overload (WO)-induced signaling through this pathway. Chronic kidney disease (CKD) and control rats were studied after 7 days of surgically induced unilateral plantaris muscle WO and a single leucine or saline load. In the basal state, 4E-BP1 phosphorylation was modestly depressed in non-WO muscle of CKD rats, whereas rpS6 phosphorylation was nearly completely suppressed. After oral leucine mTOR, S6K1 and rpS6 phosphorylation increased similarly in both groups, whereas the phospho-4E-BP1 response was modestly attenuated in CKD. WO alone activated the mTOR signaling pathway in control and CKD rats. In WO CKD, muscle leucine augmented mTOR and 4E-BP1 phosphorylation, but its effect on S6K1 phosphorylation was attenuated. Taken together, this study has established that the chronic uremic state impairs basal signaling through the mTOR anabolic pathway, an abnormality that may contribute to muscle wasting. However, despite this abnormality, leucine can stimulate this signaling pathway in CKD, although its effectiveness is partially attenuated, including in skeletal muscle undergoing sustained WO. Thus, although there is some resistance to leucine in CKD, the data suggest a potential role for leucine-rich supplements in the management of uremic muscle wasting.

scholarly journals Nutritional and endocrinological manipulation of lean deposition in forage-fed steers

1991 ◽  
Vol 66 (2) ◽  
pp. 171-185 ◽  
Author(s):  
J. M. Dawson ◽  
P. J. Buttery ◽  
M. J. Lammiman ◽  
J. B. Soar ◽  
C. P. Essex ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Lipid Composition ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Live Weight ◽  
Dry Matter Content ◽  
Semitendinosus Muscle ◽  
Intramuscular Lipid

The effect of supplementing grass silage with fishmeal on growth, muscle composition and the rate of muscle protein synthesis was investigated in young Friesian steers with and without oestradiol implants. The effect of the β-adrenergic agonist cimaterol was simultaneously investigated in animals fed on silage alone. Treatments lasted for 9 or 10 weeks. Fishmeal supplementation significantly increased animal growth rates (P < 0.001) and the weights of three dissected muscles (P < 0.001) compared with the silage-fed controls. These effects were further enhanced in animals also implanted with oestradiol. Muscle weights expressed as a proportion of body-weight were increased by fishmeal, suggesting that protein deposition had been enhanced. No further increase in the proportional muscle weights was obtained with oestradiol. Muscle dry matter content tended to be increased in both implanted and non-implanted animals receiving fishmeal compared with controls, but the proportions of protein, fat and ash were relatively constant. The intramuscular lipid composition was slightly altered by fishmeal. Muscle protein fractional synthetic rates (FSR), measured by continuous infusion of [3H]tyrosine, were increased by fishmeal in all three muscles of both implanted and non-implanted animals. There were no differences, however, due to oestradiol, over non-implanted fishmeal animals. This suggests that oestradiol may increase muscle accretion by reducing protein degradation rate. Cimaterol significantly increased longissimus dorsi (P < 0.05) and vastus lateralis (P < 0.01) muscle weights but had no effect on semitendinosus muscle weight or live-weight gain. The proportion of protein was increased (P <0.001) and the fat content reduced (P < 0.05) in all three muscles but intramuscular lipid composition was not markedly affected. Whilst methylhistidine: creatinine excretion was reduced by cimaterol, FSR were increased in the I. dorsi and v. lateralis muscles suggesting β-agonists have effects on both protein synthesis and protein degradation.

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