N τ-Methylhistidine Excretion and Myofibrillar Protein Breakdown in Patients Receiving Intravenous or Enteral Nutrition

1980 ◽  
Vol 59 (3) ◽  
pp. 211-214 ◽  
Author(s):  
I. B. Holbrook ◽  
E. Gross ◽  
P. J. Milewski ◽  
K. Shipley ◽  
M. H. Irving
Keyword(s):  
Enteral Nutrition ◽  
Muscle Protein ◽  
Myofibrillar Protein ◽  
Protein Breakdown ◽  
Breakdown Rate ◽  
Creatinine Excretion ◽  
Non Invasive ◽  
Breakdown Rates ◽  
Invasive Measurement

1. Nτ-Methylhistidine, nitrogen and creatinine were measured in the urine of 10 volunteers on normal and meat-free diets and in 10 vegetarians, and compared with the results from the urine of eight patients with intestinal fistulae on intravenous or enteral nutrition containing no meat. The values obtained were used to calculate fractional breakdown rate of myofibrillar protein. 2. There was a significant fall in the excretion of Nτ-methylhistidine and creatinine and in apparent fractional breakdown rates after 2 days on a meat-free diet. 3. One of the patients had lower, and two of the patients had higher, fractional breakdown rates compared with the vegetarians. 4. Nτ-Methylhistidine and creatinine excretion-5-be a useful and non-invasive measurement of myofibrillar protein degradation in patients on meat-free diets. Firm conclusions cannot, however, be drawn without confirmatory, direct measurement of the breakdown rates of muscle protein in vivo.

scholarly journals Skeletal-muscle growth and protein turnover

1975 ◽  
Vol 150 (2) ◽  
pp. 235-243 ◽  
Author(s):  
D J Millward ◽  
P J Garlick ◽  
R J C Stewart ◽  
D O Nnanyelugo ◽  
J C Waterlow
Keyword(s):  
Skeletal Muscle ◽  
Growth Rate ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Growth ◽  
Muscle Size ◽  
Synthesis Rate ◽  
Protein Breakdown ◽  
Breakdown Rate ◽  
Breakdown Rates

Because of turnover, protein synthesis and breakdown can each be involved in the regulation of the growth of tissue protein. To investigate the regulation of skeletal-muscle-protein growth we measured rates of protein synthesis and breakdown in growing rats during development on a good diet, during development on a marginally low-protein diet and during rehabilitation on a good diet after a period of severe protein deficiency. Rates of protein synthesis were measured in vivo with a constant intravenous infusion of [14C]tyrosine. The growth rate of muscle protein was measured and the rate of breakdown calculated as breakdown rate=synthesis rate-growth rate. These measurements showed that during development on a good diet there was a fall with age in the rate of protein synthesis resulting from a fall in capacity (RNA concentration) and activity (synthesis rate per unit of RNA). There was a fall with age in the breakdown rate so that the rate was highest in the weaning rats, with a half-life of 3 days. There was a direct correlation between the fractional growth and breakdown rates. During rehabilitation on the good diet, rapid growth was also accompanied by high rates of protein breakdown. During growth on the inadequate diet protein synthesis rates were lesss than in controls, but growth occurred because of decreased rates of protein breakdown. This compression was not complete, however, since ultimate muscle size was only one-half that of controls. It is suggested that increased rates of protein breakdown are a necessary accompaniment to muscle growth and may result from the way in which myofibrils proliferate.

scholarly journals Regulation of total and myofibrillar protein breakdown in rat extensor digitorum longus and soleus muscle incubated flaccid or at resting length

1990 ◽  
Vol 267 (1) ◽  
pp. 37-44 ◽  
Author(s):  
P O Hasselgren ◽  
M Hall-Angerås ◽  
U Angerås ◽  
D Benson ◽  
J H James ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Total Protein ◽  
Extensor Digitorum Longus ◽  
Myofibrillar Protein ◽  
Extensor Digitorum ◽  
Protein Breakdown ◽  
Breakdown Rate ◽  
Net Production ◽  
Breakdown Rates

The present study characterized total and myofibrillar protein breakdown rates in a muscle preparation frequently used in vitro, i.e. incubated extensor digitorum longus (EDL) and soleus (SOL) muscles of young rats. Total and myofibrillar protein breakdown rates were assessed by determining net production by the incubated muscles of tyrosine and 3-methylhistidine (3-MH) respectively. Both amino acids were determined by h.p.l.c. Both total and myofibrillar protein breakdown rates were higher in SOL than in EDL muscles and were decreased by incubating the muscles maintained at resting length, rather than flaccid. After fasting for 72 h, total protein breakdown (i.e. tyrosine release) was increased by 73% and 138% in EDL muscles incubated flaccid and at resting length respectively. Net production of tyrosine by SOL muscle was not significantly altered by fasting. In contrast, myofibrillar protein degradation (i.e. 3-MH release) was markedly increased by fasting in both muscles. When tissue was incubated in the presence of 1 munit of insulin/ml, total protein breakdown rate was inhibited by 17-20%, and the response to the hormone was similar in muscles incubated flaccid or at resting length. In contrast, myofibrillar protein breakdown rate was not altered by insulin in any of the muscle preparations. The results support the concepts of individual regulation of myofibrillar and non-myofibrillar proteins and of different effects of various conditions on protein breakdown in different types of skeletal muscle. Thus determination of both tyrosine and 3-MH production in red and white muscle is important for a more complete understanding of protein regulation in skeletal muscle.

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.

scholarly journals Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling

2013 ◽  
Vol 304 (3) ◽  
pp. E282-E293 ◽  
Author(s):  
Charles Harris ◽  
Donald J. Roohk ◽  
Mark Fitch ◽  
Benjamin M. Boudignon ◽  
Bernard P. Halloran ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Collagen Synthesis ◽  
Muscle Protein ◽  
Subcutaneous Fat ◽  
Skin Thickness ◽  
Breakdown Rate ◽  
Triglyceride Synthesis ◽  
Fat Depots ◽  
Breakdown Rates ◽  
Skin Collagen

Glucocorticoids are extremely effective anti-inflammatory therapies, but their clinical use is limited due to severe side effects, including osteoporosis, muscle wasting, fat redistribution, and skin thinning. Here we use heavy water labeling and mass spectrometry to measure fluxes through metabolic pathways impacted by glucocorticoids. We combine these methods with measurements of body composition in corticotropin-releasing hormone (CRH)-transgenic (Tg)+ mice that have chronically elevated, endogenously produced corticosterone and a phenotype that closely mimics Cushing's disease in humans. CRH-Tg+ mice had increased adipose mass, adipose triglyceride synthesis, and greatly increased triglyceride/fatty acid cycling in subcutaneous and abdominal fat depots and increased de novo lipogenesis in the abdominal depot. In bone, CRH-Tg+ mice had decreased bone mass, absolute collagen synthesis rates, and collagen breakdown rate. In skin, CRH-Tg+ mice had decreased skin thickness and absolute collagen synthesis rates but no decrease in the collagen breakdown rate. In muscle, CRH-Tg+ mice had decreased muscle mass and absolute protein synthesis but no decrease in the protein breakdown rate. We conclude that chronic exposure to endogenous glucocorticoid excess in mice is associated with ongoing decreases in bone collagen, skin collagen, and muscle protein synthesis without compensatory reduction (coupling) of breakdown rates in skin and muscle. Both of these actions contribute to reduced protein pool sizes. We also conclude that increased cycling between triglycerides and free fatty acids occurs in both abdominal and subcutaneous fat depots in CRH-Tg+ mice. CRH-Tg mice have both increased lipolysis and increased triglyceride synthesis in adipose tissue.

Growth Hormone-Induced Changes in Myofibrillar Protein Breakdown in Hypopituitary Children

1983 ◽  
Vol 64 (3) ◽  
pp. 315-320 ◽  
Author(s):  
F. J. Ballard ◽  
J. L. Burgoyne ◽  
F. M. Tomas ◽  
J. L. Penfold
Keyword(s):  
Growth Hormone ◽  
Hormone Treatment ◽  
Myofibrillar Protein ◽  
The Body ◽  
Protein Breakdown ◽  
Older Children ◽  
Breakdown Rate ◽  
Fractional Rate ◽  
Excretion Rates ◽  
Induced Changes

1. Creatinine and Nτ-methylhistidine excretion rates have been measured in 13 hypopituitary children to calculate the body muscle contents and rates of myofibrillar protein breakdown. Analyses have been made during periods of growth hormone withdrawal and subsequent administration. 2. The creatinine excretion rate was lower in the hypopituitary children, indicating a lower muscle content per kg body weight. This difference persisted even in children who had received growth hormone for several years. 3. Excretion of Nτ-methylhistidine was reduced by the administration of growth hormone. 4. The fractional breakdown rate of myofibrillar protein, as calculated from the Nτ-methylhistidine to creatinine molar excretion ratio, averaged 1.76%/day in the four youngest children during growth hormone withdrawal. This was significantly higher than for control children of a similar age (P < 0.02) and was reduced to the normal rate of 1.47%/day by growth hormone administration. 5. in older children the fractional rate of myofibrillar protein degradation remained in the normal range irrespective of growth hormone treatment. 6. These results are discussed in the context of the anabolic effects of growth hormone on muscle being partly explained by its action to decrease rates of protein breakdown.

scholarly journals Nitrogen balance and myofibrillar protein turnover in double muscled Belgian Blue bulls in relation to compensatory growth after different periods of restricted feeding

1998 ◽  
Vol 78 (4) ◽  
pp. 549-559 ◽  
Author(s):  
C. Van Eenaeme ◽  
M. Evrard ◽  
J. L. Hornick ◽  
P. Baldwin ◽  
M. Diez ◽  
...  
Keyword(s):  
Nitrogen Balance ◽  
Compensatory Growth ◽  
Muscle Protein ◽  
Growth Period ◽  
Myofibrillar Protein ◽  
Control Group ◽  
Protein Breakdown ◽  
Low Protein ◽  
Fattening Period ◽  
Synthesis And Degradation

Nitrogen balance and myofibrillar protein breakdown were studied in 16 double-muscled Belgian Blue bulls during a low growth period (0.5 kg d−1) (LGP) of 4 mo (L4), 8 mo (L8), or 14 mo (L14) and the subsequent fattening period (rapid growth period, RGP). The control group (CG) was given a conventional fattening diet; the others received a low-energy, low-protein diet during LGP, and the same diet as the CG during RGP. Measurements were made halfway through the LGP, l mo after the beginning of the fattening period, and 1 mo before slaughter. Nitrogen balance was about half of CG (P < 0.001) during LGP, e.g., 50.8, 21.3, 25.8, and 23.8 g d−1, for CG, L4, L8, and L14, respectively. Between LGP and RGP, N balance increased by about 18 g N d−1 above the control in the compensating groups L4, L8 and L14. This was due to the higher digestibility and the higher metabolizability of the nitrogen in the fattening diet. Lower muscle protein accretion during the LGP resulted from decreased synthesis (P < 0.001) and degradation (P < 0.05) compared with the GC. When changing to RGP different evolution patterns were observed in the three formerly restricted groups, e.g. after a short restriction (L4) both synthesis and degradation rose during the RGP but declined towards the end. After a longer restriction (L8 and L14), synthesis and degradation increased and remained high. The magnitude of these increases was inversely proportional to the length of the restriction period. Key words: Belgian Blue bulls, compensatory growth, nitrogen balance, muscle, muscle protein breakdown

Sepsis in mice stimulates muscle proteolysis in the absence of IL-6

1998 ◽  
Vol 275 (6) ◽  
pp. R1983-R1991 ◽  
Author(s):  
Arthur Williams ◽  
Jing Jing Wang ◽  
Li Wang ◽  
Xiaoyan Sun ◽  
Josef E. Fischer ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Muscle Protein ◽  
Mrna Levels ◽  
Protein Breakdown ◽  
Wild Type ◽  
Dot Blot ◽  
Muscle Protein Breakdown ◽  
L6 Myotubes ◽  
Identical Response ◽  
Breakdown Rates

We tested the role of interleukin-6 (IL-6) in sepsis-induced muscle proteolysis by determining ubiquitin mRNA levels and protein breakdown rates in incubated extensor digitorum longus muscles from septic and sham-operated IL-6 knockout and wild-type mice. In addition, the effect of treatment of mice with human recombinant IL-6 on muscle protein breakdown rates was determined. Finally, protein breakdown rates were measured in myotubes treated for up to 48 h with different concentrations of IL-6. Sepsis in wild-type mice resulted in an approximately ninefold increase in plasma IL-6 levels, whereas IL-6 was not detectable in plasma of sham-operated or septic IL-6 knockout mice. Total and myofibrillar muscle protein breakdown rates were increased by ∼30% and threefold, respectively, in septic IL-6 wild-type mice with an almost identical response noted in septic IL-6 knockout mice. Ubiquitin mRNA levels determined by dot blot analysis were increased during sepsis in muscles from both IL-6 knockout and wild-type mice, although the increase was less pronounced in IL-6 knockout than in wild-type mice. Treatment of normal mice or of cultured L6 myotubes with IL-6 did not influence protein breakdown rates. The present results suggest that IL-6 does not regulate muscle proteolysis during sepsis.

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 &lt; 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 &lt; 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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