scholarly journals Prostaglandin E2 does not regulate total or myofibrillar protein breakdown in incubated skeletal muscle from normal or septic rats

1990 ◽  
Vol 270 (1) ◽  
pp. 45-50 ◽  
Author(s):  
P O Hasselgren ◽  
O Zamir ◽  
J H James ◽  
J E Fischer
Keyword(s):  
Skeletal Muscle ◽  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Plasma Levels ◽  
Muscle Protein ◽  
Myofibrillar Protein ◽  
Protein Breakdown ◽  
Muscle Protein Breakdown

The role of prostaglandins in the regulation of muscle protein breakdown is controversial. We examined the influence of arachidonic acid (5 microM), prostaglandin E2 (PGE2) (2.8 microM) and the prostaglandin-synthesis inhibitor indomethacin (3 microM) on total and myofibrillar protein breakdown in rat extensor digitorum longus and soleus muscles incubated under different conditions in vitro. In other experiments, the effects of indomethacin, administered in vivo to septic rats (3 mg/kg, injected subcutaneously twice after induction of sepsis by caecal ligation and puncture) on plasma levels and muscle release of PGE2 and on total and myofibrillar protein breakdown rates were determined. Total and myofibrillar proteolysis was assessed by measuring production by incubated muscles of tyrosine and 3-methylhistidine respectively. Arachidonic acid or PGE2 added during incubation of muscles from normal rats did not affect total or myofibrillar protein degradation under a variety of different conditions in vitro. Indomethacin inhibited muscle PGE2 production by incubated muscles from septic rats, but did not lower proteolytic rates. Administration in vivo of indomethacin did not affect total or myofibrillar muscle protein breakdown, despite effective plasma levels of indomethacin with decreased plasma PGE2 levels and inhibition of muscle PGE2 release. The present results suggest that protein breakdown in skeletal muscle of normal or septic rats is not regulated by PGE2 or other prostaglandins.

Tumor necrosis factor induces skeletal muscle protein breakdown in rats

1991 ◽  
Vol 260 (5) ◽  
pp. E727-E730 ◽  
Author(s):  
M. N. Goodman
Keyword(s):  
Skeletal Muscle ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Muscle Protein ◽  
Nitrogen Excretion ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Breakdown ◽  
Necrosis Factor

The metabolic response to infection includes loss of lean tissue and increased nitrogen excretion. The loss of muscle tissue during infection results in large part from accelerated skeletal muscle protein breakdown. Recent studies suggest that macrophage-derived products secreted during infection may signal increased muscle proteolysis. To test this, in the present report the ability of interleukin (IL-1) and tumor necrosis factor (TNF) to enhance muscle proteolysis was examined. Young rats were injected intravenously with either recombinant human IL-1 or TNF. For comparison some rats were injected with bacterial endotoxin. Eight hours after each treatment, the extensor digitorum longus muscles were isolated and incubated in vitro to assess muscle proteolysis by measuring tyrosine and 3-methyl-L-histidine release by the incubated muscles. Treatment of rats with either IL-1, TNF, or endotoxin all induced fever, increased serum lactate, and reduced serum zinc levels. Despite similar metabolic changes, muscle proteolysis responded differently. As expected, endotoxin treatment enhanced muscle protein breakdown, whereas IL-1 treatment was without effect. On the other hand, TNF was effective in accelerating muscle protein breakdown. TNF addition in vitro failed to enhance muscle proteolysis by incubated muscles, suggesting that its effects may be mediated in an indirect manner; however, a direct mode of action cannot yet be ruled out. Overall, the data indicate that the acute administration of TNF can signal increased muscle proteolysis similar to that observed during infection.

Role of Interleukin-6 in Skeletal Muscle Protein Breakdown and Cathepsin Activity in vivo

1996 ◽  
Vol 28 (5) ◽  
pp. 361-366 ◽  
Author(s):  
J. Fujita ◽  
T. Tsujinaka ◽  
C. Ebisui ◽  
M. Yano ◽  
H. Shiozaki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Interleukin 6 ◽  
Muscle Protein ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Breakdown ◽  
Cathepsin Activity

Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx

2009 ◽  
Vol 296 (4) ◽  
pp. R893-R901 ◽  
Author(s):  
Ambikaipakan Balasubramaniam ◽  
Rashika Joshi ◽  
Chunhua Su ◽  
Lou Ann Friend ◽  
Sulaiman Sheriff ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Burn Injury ◽  
Muscle Protein ◽  
Ubiquitin Ligases ◽  
Myofibrillar Protein ◽  
E3 Ubiquitin Ligases ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Breakdown

We previously determined that ghrelin synthesis was downregulated after burn injury and that exogenous ghrelin retained its ability both to stimulate food intake and to restore plasma growth hormone levels in burned rats. These observations and the finding that anabolic hormones can attenuate skeletal muscle catabolism led us to investigate whether ghrelin could attenuate burn-induced skeletal muscle protein breakdown in rats. These studies were performed in young rats (50–60 g) 24 h after ∼30% total body surface area burn injury. Burn injury increased total and myofibrillar protein breakdown in extensor digitorum longus (EDL) muscles assessed by in vitro tyrosine and 3-methyl-histidine release, respectively. Continuous 24-h administration of ghrelin (0.2 mg·kg−1·h−1) significantly inhibited both total and myofibrillar protein breakdown in burned rats. Ghrelin significantly attenuated burn-induced changes in mRNA expression of IGFBP-1 and IGFBP-3 in liver. In EDL, ghrelin attenuated the increases in mRNA expression of the binding proteins, but had no significant effect on reduced expression of IGF-I. Ghrelin markedly reduced the elevated mRNA expression of TNF-α and IL-6 in EDL muscle that occurred after burn. Moreover, ghrelin normalized plasma glucocorticoid levels, which were elevated after burn. Expression of the muscle-specific ubiquitin-ligating enzyme (E3) ubiquitin ligases MuRF1 and MAFbx were markedly elevated in both EDL and gastrocnemius and were normalized by ghrelin. These results suggest that ghrelin is a powerful anticatabolic compound that reduces skeletal muscle protein breakdown through attenuating multiple burn-induced abnormalities.

scholarly journals The retention and metabolism of Nτ-methylhistidine by cockerels: implications for the measurement of muscle protein breakdown determined from the excretion of Nτmethylhistidine in excreta

1987 ◽  
Vol 57 (3) ◽  
pp. 467-478 ◽  
Author(s):  
C. I. Harris ◽  
G. Milne ◽  
Ruth McDiarmid
Keyword(s):  
Skeletal Muscle ◽  
Subcutaneous Injection ◽  
Muscle Protein ◽  
Protein Breakdown ◽  
Reliable Index ◽  
Muscle Protein Breakdown ◽  
Thigh Muscles ◽  
Daily Excretion ◽  
Total Pool

1. Excreta were collected for four consecutive days from 4- to 18-week-old cockerels following subcutaneous injection of Nτ-[14CH3]methylhistidine.2. The recoveries of radioactivity in excreta were incomplete and progressively decreased with increasing age.3. Most of the radioactivity not recovered in excreta after 4 d was found in skeletal muscle where > 55% of the radioactivity present was in the Nτ-methylhistidine-containing dipeptide, balenine.4. This peptide appeared to be relatively stable so that most of the labelled Nτ-methylhistidine incorporated was not released during the period of the recovery measurements.5. The total pool of non-protein bound Nτ-methylhistidine (free Nτ-methylhistidine+balenine) in pectoral and mixed thigh muscles increased with age and relative to the daily excretion of Nτ-methylhistidine. At 18 weeks the pool was 3.3 times the daily excretion of Nτ-methylhistidine.6. These observations account for the decreasing recoveries of radioactivity in excreta described previously, due to progressive dilution of labelled Nτ-methylhistidine in an expanding pool of non-protein-bound Nτ-methylhistidine, part of which was relatively stable.7. It is concluded that excretion of Nτ-methylhistidine by 4- to 18-week-old cockerels cannot be used as a reliable index of muscle protein breakdown in vivo.

Assessment in vitro and in vivo of muscle degradation in chronic skeletal muscle myopathy of alcoholism

1985 ◽  
Vol 68 (6) ◽  
pp. 693-700 ◽  
Author(s):  
Finbarr C. Martin ◽  
Timothy J. Peters
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Protein Breakdown ◽  
Turnover Rates ◽  
Alcoholic Myopathy ◽  
Biochemical Journal ◽  
Muscle Breakdown

1. Muscle protein breakdown in vivo has been studied by measurements of urinary 3-methylhistidine/creatinine ratios. No differences were found between control subjects and chronic alcoholics either with or without proximal muscle wasting or cirrhosis. 2. Calculation of muscle turnover rates, with the correction of Afting et al. (1981, Biochemical Journal, 200, 449-452) for non-skeletal muscle contributions of 3-methylhistidine and creatinine, showed lower values for alcoholics compared with controls. 3. Tissue activities of a neutral protease, assayed by a novel, rapid and sensitive fluorimetric method, were similar in patients and controls. The activity did not vary with severity of atrophy or the presence of cirrhosis. 4. No evidence was therefore obtained to suggest that alcoholic myopathy is due to increased muscle breakdown.

scholarly journals Myofibrillar Protein Abundance and Anabolic Signaling in Myotubes Depleted of E1 Alpha Subunit of Branched-Chain Ketoacid Dehydrogenase Complex

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 642-642
Author(s):  
Glory Madu ◽  
Olasunkanmi Adegoke
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Content ◽  
Muscle Protein ◽  
Essential Amino Acids ◽  
Myofibrillar Protein ◽  
L6 Myotubes ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase

Abstract Objectives Branched-chain amino acids (BCAAs) are essential amino acids that are crucial for skeletal muscle anabolism. Thus, alterations in their levels are associated with muscle atrophic diseases such as cancer, chronic inflammatory and neurological disorders. Others have linked impairments in BCAA metabolism to the development of insulin resistance and its sequelae. Compared to the effects of theses amino acids, much less is known on how impairment in BCAA catabolism affects skeletal muscle. BCAA catabolism starts with the reversible transamination by the mitochondrial enzyme branched-chain aminotransferase 2 (BCAT2). This is followed by the irreversible carboxylation, catalyzed by branched-chain ketoacid dehydrogenase (BCKD) complex. We have shown that BCAT2 and BCKD are essential for the differentiation of skeletal myoblasts into myotubes. Here, we investigated the effect of depletion of BCAT2 or of E1a subunit of BCKD in differentiated myotubes. Methods On day 4 of differentiation, L6 myotubes were transfected with the following siRNA oligonucleotides: scrambled (control), BCAT2, or E1a subunit of BCKD. Results Forty-eight hours after transfection, compared to control or BCAT2 siRNA group, we observed improved myotube structure in BCKD-depleted cells. BCKD depletion augmented myofibrillar protein levels: myosin heavy chain (MHC, 2-fold) and tropomyosin (4-fold), P < 0.05, n = 3. To further analyze the increase in myofibrillar protein content, we examined signaling through mTORC1 (mechanistic target of rapamycin complex 1), a vital complex necessary for skeletal muscle anabolism. BCKD depletion increased the phosphorylation of mTORC1 upstream activator AKT (52%, P < 0.05, n = 3), and of mTORC1 downstream substrates by 25%-86%, consistent with the increase in myofibrillar proteins. Finally, in myotubes treated with the catabolic cytokine (tumor necrosis factor-a), BCKD depletion tended to increase the abundance of tropomyosin (a myofibrillar protein). Conclusions We showed that depletion of BCKD enhanced myofibrillar protein content and anabolic signaling.  If these data are confirmed in vivo, development of dietary and other interventions that target BCKD abundance or functions may promote muscle protein anabolism in individuals with muscle wasting conditions. Funding Sources MHRC, NSERC York U.

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