Biomedical subjects

D Taillandier

Publications and source records attributed to D Taillandier.

24 records · Page 2Linked to original sources

PubMed1995

Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats. Lack of regulation of the ubiquitin-proteasome proteolytic pathway in aging.

We studied glucocorticoid-induced muscle wasting and subsequent recovery in adult (7-mo-old) and old (22-mo-old) rats, since the increased incidence of various disease states may result in glucocorticoids hypersecretion in aging. Adult and old rats received dexamethasone in their drinking water and were then allowed to recover. Muscle wasting occurred more rapidly in old rats and the recovery of muscle mass was impaired, suggesting that glucocorticoids may be involved in the emergence of muscle atrophy with advancing age. According to measurements in incubated epitrochlearis muscles, dexamethasone-induced muscle wasting mainly resulted from increased protein breakdown in the adult, but from depressed protein synthesis in the aged animal. Increased expression of cathepsin D, m-calpain, and ubiquitin was observed in the muscles from both dexamethasone-treated adult and old rats. By contrast, the disappearance of the stimulatory effect of glucocorticoids on protein break-down in aging occurred along with a loss of ability of steroids to enhance the expression of the 14-kD ubiquitin carrier protein E2, which is involved in protein substrates ubiquitinylation, and of subunits of the 20 S proteasome (the proteolytic core of the 26 S proteasome that degrades ubiquitin conjugates). Thus, if glucocorticoids play any role in the progressive muscle atrophy seen in aging, this is unlikely to result from an activation of the ubiquitin-proteasome proteolytic pathway.

Aging↗

PubMed1994

Increased ATP-ubiquitin-dependent proteolysis in skeletal muscles of tumor-bearing rats.

Little information is available on proteolytic pathways responsible for muscle wasting in cancer cachexia. Experiments were carried out in young rats to demonstrate whether a small (< 0.3% body weight) tumor may activate the lysosomal, Ca(2+)-dependent, and/or ATP-ubiquitin-dependent proteolytic pathway(s) in skeletal muscle. Five days after tumor implantation, protein mass of extensor digitorum longus and tibialis anterior muscles close to a Yoshida sarcoma was significantly reduced compared to the contralateral muscles. According to in vitro measurements, protein loss totally resulted from increased proteolysis and not from depressed protein synthesis. Inhibitors of lysosomal and Ca(2+)-dependent proteases did not attenuate increased rates of proteolysis in the atrophying extensor digitorum longus. Accordingly, cathepsin B and B+L activities, and mRNA levels for cathepsin B were unchanged. By contrast, ATP depletion almost totally suppressed the increased protein breakdown. Furthermore, mRNA levels for ubiquitin, 14 kDa ubiquitin carrier protein E2, and the C8 or C9 proteasome subunits increased in the atrophying muscles. Similar adaptations occurred in the muscles from cachectic animals 12 days after tumor implantation. These data strongly suggest that the activation of the ATP-ubiquitin-dependent proteolytic pathway is mainly responsible for muscle atrophy in Yoshida sarcoma-bearing rats.

Animals↗

PubMed1994

Regulation of ATP-ubiquitin-dependent proteolysis in muscle wasting.

Protein breakdown plays a major role in muscle growth and atrophy. However, the regulation of muscle proteolysis by nutritional, hormonal and mechanical factors remains poorly understood. In this review, the methods available to study skeletal muscle protein breakdown, and our current understanding of the role of 3 major proteolytic systems that are well characterized in this tissue (ie the lysosomal, Ca(2+)-dependent and ATP-ubiquitin-dependent proteolytic pathways) are critically analyzed. ATP-ubiquitin-dependent proteolysis is discussed in particular since recent data strongly suggest that this pathway may be responsible for the loss of myofibrillar proteins in many muscle-wasting conditions in rodents. In striking contrast to either the lysosomal or the Ca(2+)-dependent processes, ATP-ubiquitin-dependent protein breakdown is systematically influenced by nutritional manipulation (fasting and dietary protein deficiency), muscle activity and disuse (denervation atrophy and simulated weightlessness), as well as pathological conditions (sepsis, cancer, trauma and acidosis). The hormonal control of this pathway, its possible substrates, rate-limiting step, and functional associations with other proteolytic systems are discussed.

Adenosine Triphosphate↗

PubMed1993

Effects of protein supplementation during prolonged exercise at moderate altitude on performance and plasma amino acid pattern.

The effects of two levels of protein intake on muscle performance and energy metabolism were studied in humans submitted to repeated daily sessions of prolonged exercise at moderate altitude. For this purpose, 29 healthy males, were exposed to seven successive stages of ski-mountaineering at altitudes between 2500 and 3800 m, and to an isocaloric diet (4000 kcal.day-1, 16,760 kJ.day-1) with either 1.5 g.kg-1.day-1 (C group, n = 14), or 2.5 g.kg-1.day-1 (PR group, n = 15) protein intake. Measurements made after the ski-mountaineering programme did not show any change in body mass. The peak torque during maximal isometric voluntary contraction (MVC) of the quadriceps muscle was unaffected by the repeated exercises, whereas the endurance time at 50% MVC was decreased in PR subjects (-26.8%, P < 0.001). Increased levels of both free fatty acids (+ 147%, P < 0.001) and glycerol (+ 170%, P < 0.001) observed in C subjects would suggest that lipolysis was enhanced after the repeated exercise. The plasma amino acid pattern was altered after completion of the ski-mountaineering programme; the plasma concentration of the three branched-chain amino acids (BCAA) was significantly decreased in C subjects, whereas the higher level of protein intake (PR group) greatly minimized the exercise-induced decrease in serum BCAA.

Altitude↗

PubMed1993

Role of protein intake on protein synthesis and fiber distribution in the unweighted soleus muscle.

Protein turnover in skeletal muscle is very sensitive to protein intake. To examine whether protein intake is able to affect protein synthesis in the atrophied soleus muscle, the effects of a high-protein (30%, HP) and a medium-protein (15%, MP) diet were studied in rats after 21 days of hindlimb unweighting. Three weeks of unweighting induced a sharp decrease in food intake (30%). The fractional rate of protein synthesis (ks) was determined in vivo in the slow-twitch soleus muscle by use of a flooding-dose method. With respect to pair-fed animals, a significant reduction in ks occurred (33%) in MP non-weight-bearing rats, whereas it was of lesser magnitude and not significant in HP rats. In the atrophied soleus muscle of non-weight-bearing MP rats, a large decrease (42%) in type I fiber distribution was accompanied by an increase in intermediate and type IIa fibers. By contrast, a higher percentage of type I fiber was maintained with the HP diet. However, the HP diet had no beneficial effect in preventing the decrease in either type I fiber cross-sectional area (65%) or the average decrease in absolute myofibrillar and mitochondrial volumes (69 and 52%, respectively). These results demonstrate that an HP intake did not prevent soleus muscle atrophy but may sustain protein synthesis and partly preserve fiber type distribution without affecting the ultrastructural composition of fibers. Because the circulating level of free 3,5,3'-triiodothyronine was reduced by 14% with the HP diet, this effect on fiber type distribution, and possibly protein synthesis, may involve thyroid hormones.

Animals↗

PubMedDate not supplied

Ubiquitin-proteasome-dependent proteolysis in skeletal muscle.

The ubiquitin-proteasome proteolytic pathway has recently been reported to be of major importance in the breakdown of skeletal muscle proteins. The first step in this pathway is the covalent attachment of polyubiquitin chains to the targeted protein. Polyubiquitylated proteins are then recognized and degraded by the 26S proteasome complex. In this review, we critically analyse recent findings in the regulation of this pathway, both in animal models of muscle wasting and in some human diseases. The identification of regulatory steps of ubiquitin conjugation to protein substrates and/or of the proteolytic activities of the proteasome should lead to new concepts that can be used to manipulate muscle protein mass. Such concepts are essential for the development of anti-cachectic therapies for many clinical situations.

Animals↗