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Biomedical subjects

D J Millward

Publications and source records attributed to D J Millward.

At least 109 records · Page 6Linked to original sources
PubMed1981

The extent and nature of protein degradation in the tissues during development.

Protein turnover, defined as the degradation and replacement of proteins, appears to vary between most adult species in the same way as metabolic rate, i.e. as W0.75, although it may be a little lower in man. During development in the rat it also varies as metabolic rate. Thus P Total = 14.7 W0.53kg per day. Most of this turnover occurs in nonmuscle tissues (P = 11.3 W0.50kg per day) with protein turnover in muscle described by P = 3.53 W0.69kg per day. Mechanisms for protein degradation in liver and muscle involve lysosomes although the morphology of the lysosomal system in muscle is different from that in liver. However, heterogeneous turnover is a feature of proteins in both issues including the principal myofibrillar proteins. While the reaction order of protein synthesis can reasonably be described as zero order--a fixed rate per unit of DNA--there is less certainty about degradation. It is postulated that structural and functional characteristics of the cytoplasm of cells determine the accessibility of cellular protein to the degrading system. As a result, a first order rate for a particular cell type is fixed, and this determines the magnitude of the protein-DNA ratio or the functional-cell size. The first order degradation rate of the cytoplasmic protein also determines the specific activity of the degrading enzymes.

Animals↗
PubMed1981

Characteristics of skeletal muscle growth and protein turnover in a fast-growing rat strain.

1. Protein turnover and muscle composition has been studied in rat skeletal muscle throughout development in a relatively-fast-growing rat strain. 2. Muscle growth involved an increase in the total DNA and in the DNA-unit size as indicated by proteins: DNA. As a result of the latter increase together with no change in RNA: DNA, the RNA concentration fell throughout development. 3. Rates of protein synthesis measured in vivo by the continuous intravenous infusion method fell throughout development from 15.6%/d at 25 d to 4.46%/d at 320 d, and these changes reflected mainly the fall in RNA concentration, since there was no marked change in the rate of protein synthesis per unit RNA. 4. The rate of protein degradation, measured as the difference between rates of protein synthesis and growth, fell from 9.82%/d at 25 d to 4.46%/d at 320 d. 5. When these changes in protein turnover throughout development are compared with measurements made previously in a slow-growing strain it would appear that the faster growth was achieved as a result of increased efficiency of protein synthesis (defined as net synthesis: over-all synthesis) and this occurred mainly because of lower rates of protein degradation.

Aging↗
PubMed1981

Protein degradation in skeletal muscle: implications of a first order reaction for the degradative process.

The rate of protein degradation is usually thought to be first order, i.e. determined by the nature of the protein as a substrate. It is not immediately apparent if this is the case for the overall process in the cell since rates of turnover of individual proteins may vary between tissues. In muscle the characteristics of protein turnover in relation to DNA-unit size have led to the development of a model for protein turnover in which degradation rates are determined by the rate of dissociation of protein subunits from the myofibrillar matrix. This is a necessary step if heterogeneous turnover occurs and if degradation and resynthesis of myofibrillar proteins occurs peripherally to the myofibril. As a result a first order rate can be envisaged so that during muscle growth the protein mass per unit DNA increases to a characteristic amount thus determining the specific activity of the degrading system. Such a mechanism may apply to all cells.

Actins↗
PubMed1980

Quantitative importance of non-skeletal-muscle sources of N tau-methylhistidine in urine.

Direct measurement of N tau-methylhistidine turnover in skeletal muscle, skin and gastrointestinal muscle indicates that these three tissues contribute only 24.9, 6.8 and 9.8% of the total urinary excretion. Measurement of the decay rate of radioactively labelled N tau-methylhistidine in urine indicates that skeletal muscle accounts for 74.5% of the urinary excretion and this is probably an overestimate. These results suggest that the common assumption, that N tau-methylhistidine in urine originates almost entirely from skeletal muscle, may be wrong.

Animals↗
PubMed1980

Protein turnover during skeletal muscle hypertrophy.

Skeletal muscle hypertrophy has been investigated in several models including denervation, increased work induced by tenotomy of a synergist, and the addition of weights to the wing of a chicken. The stimulus for growth probably involves passive stretch along with increased tension development induced by the stretch reflex in innervated muscles. In early studies of hypertrophy of rat soleus and plantaris muscles, turnover measurements were interpreted as indicating increased protein synthesis and decreased degradation as the mechanism for the hypertrophy. However, these conclusions are probably unjustified. In particular it has been shown that there is a marked increase in reutilization and isotope recycling in muscle during hypertrophy. Several studies indicate that both protein synthesis and degradation are increased during hypertrophy. This has been shown in the transient hypertrophy of the denervated hemidiaphragm. During hypertrophy of the innervated anterior latissimus dorsi of chickens, there are increases in protein synthesis and degradation to the extent that as much as two-thirds of the total increase in synthesis may be associated with increased turnover or "wastage" and only one-third with growth.

Animals↗
PubMed1979

The effect of surgical trauma on muscle protein turnover in rats. A serious methodological misunderstanding.

The reported rates of protein degradation in a recent paper on the effect of surgical trauma on muscle protein turnover [Hoover-Plow & Clifford (1978) Biochem. J. 176, 137--142] have no real meaning because of a serious methodological misunderstanding by the authors. In addition, there are problems involved in the determination of synthesis rates, so that the reported effects of trauma on muscle protein turnover can be discounted.

Animals↗
PubMed1979

Protein degradation and the regulation of protein balance in muscle.

The rate of of protein degradation in muscle changes in many states but the nature of these changes is often paradoxical. Thus there can be increases during growth (anabolic increases) as well as during wasting (catabolic increases). Decreases can occur during growth (anabolic decreases) as well as during wasting (catabolic decreases). These changes are observed in man (as judged by changes in 3-methylhistidine excretion) and in experimental animals. The nature of the changes is not understood but it is possible that muscle growth induces increased degradation as part of the accompanying myofibre remodelling. The rate of protein degradation can also be influenced by thyroid status, since in thyroid deficiency degradation is reduced and can be stimulated by triiodothyronine. This response is independent of changes in muscle growth. Finally, acute exercise suppresses protein degradation in vivo in man as well as suppressing protein synthesis (in vivo in rats). When protein degradation rates change, acid proteinase activities also change in muscle. The anabolic increase in degradation appears to involve increases in mainly cathepsin D whereas catabolic increases in degradation are associated with an increase mainly in pepstatin-insensitive acid autolytic activity.

Adult↗
PubMed1978

Turnover of muscle protein in the fowl (Gallus domesticus). Rates of protein synthesis in fast and slow skeletal, cardiac and smooth muscle of the adult fowl.

Rates of protein synthesis in skeletal, cardiac and smooth muscle of fully grown fowl (Gallus domesticus) were determined in vivo by means of the constant infusion method using [14C]proline. In the anterior latissimus dorsi muscle, containing predominantly slow fibres, the average synthesis rate of non-collagen muscle proteins was 17.0 +/- 3.1% per day, a value higher than that obtained for cardiac muscle (13.8 +/- 1.3% per day) and for smooth muscle of the gizzard (12.0 +/- 1.9% per day). In the posterior latissimus dorsi muscle, containing predominantly fast fibres, synthesis rates were much lower (6.9 +/- 1.8% per day). In each case these average rates for the non-collagen protein were similar to the average rate for the sarcoplasmic and myofibrillar protein fractions. The RNA concentration of these four muscles showed that relative rates of protein synthesis were determined mainly by the relative RNA concentrations. The rate of protein synthesis per unit of DNA (the DNA activity) was similar in the two skeletal muscles, but somewhat lower in cardiac muscle and gizzard, possibly reflecting the larger proportion of less active cell types in these two muscles. These quantitative aspects of protein turnover in the two skeletal muscles are discussed in terms of the determination of ultimate size of the DNA unit, and in relation to muscle ultrastructure.

Animals↗
PubMed1978

Turnover of muscle protein in the fowl. Changes in rates of protein synthesis and breakdown during hypertrophy of the anterior and posterior latissimus dorsi muscles.

Measurements were made of the growth and of the changes in rates of protein turnover in the anterior latissimus dorsi muscle of the adult fowl in response to the attachment of a weight to one wing. Over 58 days there was a 140% increase in the protein content with similar increases in the RNA and DNA contents. The fractional rate of protein synthesis, measured by the continuous-infusion technique using [14C]proline, increased markedly during hypertrophy. This increase was mediated initially (after 1 day) by an increase in the RNA activity but at all other times reflected the higher RNA content. The rate of protein degradation, calculated from the difference between the synthesis and growth rates, appeared to increase and remain elevated for at least 4 weeks. At no time was there any suggestion of a fall in the rate of degradation. The following events are discussed as central to the changes that occur during skeletal-muscle hypertrophy. 1. Nuclear proliferation is necessary to maintain the characteristic synthesis rate because of the inability of existing nuclei to 'manage' increased protein synthesis for more than a limited period. 2. The increased protein breakdown during hypertrophy is consistent with the known over-production of a new muscle fibres and may indicate some 'wastage' during the growth. Such wastage may also be associated with myofibrillar proliferation. 3. Muscle stretch must be recognized as the major activator of growth and as such can be compared with the 'pleiotypic activators' that have been described for cells in culture.

Animals↗
PubMed1978

Turnover of muscle protein in the fowl. Collagen content and turnover in cardiac and skeletal muscles of the adult fowl and the changes during stretch-induced growth.

The collagen content and the rate of collagen synthesis were measured in the anterior and posterior latissimus dorsi muscles and in heart from fully grown fowl. This was done by measuring the proline/hydroxyproline ratios in the muscle and by a constant infusion of [(14)C]proline. These measurements were also made during the hypertrophy of the anterior muscle in response to the attachment of a weight to one wing of the fowl. In the non-growing muscles the collagen content was higher in the anterior muscle (22.8% of total protein) than in the posterior muscle (9.5% of total protein) and lowest in the heart (3.8% of total protein). In the two skeletal muscles a little over half of the collagen was accounted for by internal collagen (i.e. perimysium and endomysium). Collagen synthesis in these non-growing muscles occurred at 0.59%/day in each of the two skeletal muscles and at 0.88%/day in the cardiac muscle. During hypertrophy the collagen content of the anterior muscle increased, but not as fast as intracellular protein, so that after 58 days the concentration had fallen from 22.8 to 14.4% of total protein. This may have resulted from an incomplete production of the epimysial sheath, since the concentration of internal collagen did not fall and as a result accounted for over 80% of the total in the enlarged muscle. Collagen synthesis increased 8-fold during the first week of the hypertrophy, but never amounted to more than 4% of the total muscle protein synthesis. When the net accumulation of collagen is compared with the increased rate of synthesis it is concluded that between 30 and 70% of the newly synthesized collagen may have been degraded.

Animals↗