Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.25.1 (proteasome)
28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the role of calpains in myofibrillar protein degradation in skeletal muscle and the regulation of their activity in vivo, we studied the effects of fasting on gene expression of calpains and calpastatin in the skeletal muscle of rabbits. In response to fasting, myofibrillar protein degradation increased 2-fold and mRNA levels of calpain I, calpain II and calpastatin were also increased. However, calpain and calpastatin activities remained unchanged. To investigate this discrepancy, we analysed polysomal calpain mRNA. Results indicated that fasting caused a 2-fold increase in the loading of calpain I and II mRNAs on ribosomes. Thus transcription of genes encoding calpain may be increased during fasting to ensure adequate synthesis of the proteinases needed to mobilize muscle protein reserves. The effect of fasting on calpain and calpastatin mRNA expression is shared by cathepsin D and proteasome C2 but not by beta-actin, implying that fasting invokes control of several proteolytic systems in skeletal muscle and underscores the possibility that each proteolytic system plays a role in the adaptation of skeletal muscle to the fasted state.
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PMID:Gene expression of calpains and their specific endogenous inhibitor, calpastatin, in skeletal muscle of fed and fasted rabbits. 141 70

Four intracellular proteases partially purified from liver preferentially degraded the oxidatively modified (catalytically inactive) form of glutamine synthetase. One of the proteases was cathepsin D which is of lysosomal origin; the other three proteases were present in the cytosol. Two of these were calcium-dependent proteases with different calcium requirements. The low-calcium-requiring type (calpain I) accounted for most of the calcium-dependent activity of both mouse and rat liver. The calcium-independent cytosolic protease, referred to as the alkaline protease, has a molecular weight of 300,000 determined by gel filtration. Native glutamine synthetase was not significantly degraded by the cytosolic proteases at physiological pH, but oxidative modification of the enzyme caused a dramatic increase in its susceptibility to attack by these proteases. In contrast, trypsin and papain did degrade the native enzyme and the degradation of modified glutamine synthetase was only 2- to 4-fold more rapid. Adenylylation of glutamine synthetase had little effect on its susceptibility to proteolysis. Although major structural modifications such as dissociation, relaxation, and denaturation also increased the rate of degradation, the oxidative modification is a specific type of covalent modification which could occur in vivo. Oxidative modification can be catalyzed by a variety of mixed function oxidase systems present within cells and causes inactivation of a number of enzymes. Moreover, the presence of cytosolic proteases which recognize the oxidized form of glutamine synthetase suggests that oxidative modification may be involved in intracellular protein turnover.
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PMID:Preferential degradation of the oxidatively modified form of glutamine synthetase by intracellular mammalian proteases. 285 20

The activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT), both enzymes of collagen biosynthesis, were measured in the gastrocnemius, soleus, and tibialis anterior muscles of rats after bilateral cast-immobilization of the muscles in lengthened and shortened positions for one and three weeks. The activities of muscular proteolytic and hydrolytic enzymes cathepsin D (CD), beta-glucuronidase (beta-GU), alkaline protease (AP), and the rate of acid autolysis (AA) were also studied. The biochemical results were compared to the morphologic changes by light microscopy. Compared to the results for a control group, there was a decrease of 37% and 53% in the specific PH activity of shortened gastrocnemius and soleus, respectively, after three weeks of immobilization. The corresponding decrease in GGT of the shortened gastrocnemius was 47%. At the same time, PH and GGT in the lengthened plantarflexors were at the control level. The proteolytic activities of the shortened plantarflexors were generally higher (CD by approximately 30%, beta-GU of gastrocnemius by 81%, AP of soleus by 63%, AA of gastrocnemius by 34%, and AA of soleus by 56%) than those of the lengthened ones. Light microscopy of the shortened muscles showed numerous atrophic fibers, but no pronounced inflammatory response in the disused muscle tissue. The results suggest that increased proteolysis and wasting of muscle tissue during cast-immobilization is associated with adaptive responses in the metabolism of the muscular collagen network.
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PMID:Collagen synthesis and proteolytic activities in rat skeletal muscles: effect of cast-immobilization in the lengthened and shortened positions. 305 21

The activities of cathepsin D (CD), beta-glucuronidase (beta-GU), alkaline protease (AKP), and the rate of acid autolysis (AA) were measured in gastrocnemius, soleus, and tibialis anterior muscles of the rat after bilateral cast immobilization in the middle position for one and three weeks. The effects of daily indirect electric stimulation on the proteolytic activities of immobilized muscles were also studied. In gastrocnemius and tibialis anterior, electric stimulation partially prevented the loss of muscle weight after immobilization for one week. Activities of CD and beta-GU were highest in the soleus, but the activities did not change therein after immobilization or electric stimulation. In gastrocnemius, the activities of CD and AKP and the AA rate increased significantly after immobilization. Electric stimulation during immobilization seemed to prevent the increase of CD and AKP activities significantly after one (CD) and three (AKP) weeks immobilization. In tibialis anterior, the activities of CD and AKP and the AA rate increased significantly in the stimulated muscles after immobilization for three weeks. Both in the gastrocnemius and tibialis anterior the beta-GU activity increased significantly in the stimulated muscles. The results suggest that during the disuse atrophy process and electric stimulation of immobilized muscles, rat hind-limb muscles differ in acid and alkaline proteolytic responses.
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PMID:Acid and alkaline proteolytic activities of cast-immobilized rat hind-limb muscles after electric stimulation. 330 95

Protein synthesis and degradation and net uptake and release of amino acids and minerals were examined in the perfused hemicorpus of bilaterally nephrectomized and sham-operated control rats. Animals were studied 30 h after surgery. In comparison with controls, uremic rats had greater urea N appearance (net urea generation) and lower plasma and muscle concentrations of most amino acids. Muscle protein synthesis was not altered, but protein degradation was greater in uremic versus sham rats. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium, and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. ATP, creatine phosphate, cAMP, and activities of cathepsin B1, cathepsin D, and alkaline protease were not different in muscles of the uremic versus sham rats. Thus, in acutely uremic rats there is increased protein wasting in the hemicorpus due to enhanced protein degradation. The enhanced protein degradation does not appear to be due to increased muscle cathepsin B1, cathepsin D, or alkaline protease activities.
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PMID:Protein and amino acid metabolism in posterior hemicorpus of acutely uremic rats. 630 4

The role of cardiac lysosomal and nonlysosomal protease alterations in the development of the cardiomyopathy that occurs in genetically diabetic C57BL/KsJ db/db mice has been examined. The db/db mice and age-matched controls were sacrificed between 7 and 24 weeks of age. Cathepsin D activity, myofibrillar alkaline protease (MAP) activity (including serine protease activity), and Ca2+-activated protease activity were determined by using [3H]acetyl-casein as substrate. There is a significant decrease in cathepsin D, MAP, and serine protease activities in the myocardium of 7- to 20-week old diabetic mice with a rebound of these activities toward normal levels by 24 weeks of age. Cathepsin D and MAP activities are inversely related to heart weight in diabetic mice with the higher levels being recorded in association with the most pronounced decrease in heart weight. In contrast, Ca2+-activated protease activity in the hearts of diabetic mice does not differ significantly from controls throughout the period of observation. The results suggest that both lysosomal cathepsin D and nonlysosomal MAP may mediate the accelerated cardiac muscle degradation that occurs in the late stage of diabetic cardiomyopathy in the db/db mice.
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PMID:Lysosomal and nonlysosomal proteolytic activities in experimental diabetic cardiomyopathy. 632 62

Two-kidney, one clip Goldblatt hypertension of 2, 4 and 8 weeks duration was induced in 100-g male Wistar-Kyoto rats. Nucleic acid content was determined in the isolated cardiac muscle cells from the left ventricle. The profile for several major proteolytic activities in either isolated cardiac muscle cells or left ventricle preparations was also studied, using [3H]acetyl-casein as substrate. From the soluble fraction of the tissue or cell preparation, a pH 6 proteolytic activity, two forms of calcium-activated protease as well as cathepsin D were identifiable by inhibitor assay or DEAE-cellulose chromatography. From the myofibrillar fraction of the same preparation, two kinds of proteolytic activity were detected at alkaline pH: a phenylmethylsulfonyl fluoride (PMSF) inhibitable activity that was serine protease-like and the other a N-ethylmaleimide (NEM) inhibitable activity that resembled Ca2+-activated protease. At 2 weeks of hypertension, there was a significant increase in the pH 6 proteolytic activity as well as the calcium-activated protease I and the NEM-inhibitable alkaline protease activities, while the other identifiable proteolytic activities remained unchanged. Lysosomal cathepsin D showed a rise in activity only after 8 weeks of hypertension. These results may be related to the development of myocyte necrosis and lysis that occur in this model of hypertensive cardiomyopathy.
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PMID:Proteolytic activities in hypertensive cardiomyopathy of rats. 634 96

The activities of four lysosomal and two nonlysosomal hydrolases were studied in skeletal muscle biopsy samples from patients with neuromuscular diseases and from controls. beta-Glucosaminidase activity was increased in polymyositis. beta-Glucuronidase and alkaline protease activities were elevated in muscular dystrophy in adults, whereas cathepsin D activity was increased in amyotrophic lateral sclerosis. There were significant correlations between the activities of lysosomal and nonlysosomal hydrolases. The activity of beta-glucuronidase, beta-glucosaminidase, alkaline protease, and dipeptidyl aminopeptidase IV showed a positive correlation with the severity of muscular atrophy. The activities of these hydrolases and the activity of dipeptidyl aminopeptidase I correlated positively with the activities of muscular galactosylhydroxylysyl glucosyltransferase and with the serum concentration of type III procollagen aminoterminal propeptide. The results suggest that in neuromuscular diseases the lysosomal and nonlysosomal pathways for muscle degradation are affected concomitantly with collagen biosynthesis.
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PMID:Lysosomal and nonlysosomal hydrolases of skeletal muscle in neuromuscular diseases. 635 16

Protein synthesis and degradation and net uptake and release of amino acids and minerals were investigated in the perfused hemicorpus of acutely uremic and control Sprague-Dawley rats. Rats underwent bilateral nephrectomy or sham surgery and were studied 30 hr after surgery. The uremic rats displayed greater urea N appearance (net urea generation), lower plasma and muscle concentrations of most amino acids, and increased muscle protein degradation as compared to control rats. Muscle protein synthesis was slightly but not significantly decreased in the uremic animals. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. Muscle ATP, creatine phosphate, cyclic-AMP, and activities of cathepsin B1, cathepsin D, and alkaline protease were not different in the uremic and sham rats. These data provide evidence that acutely uremic rats sustain increased muscle protein wasting which is due to enhanced protein degradation. The increased protein degradation does not appear to be due to enhanced activities of muscle cathepsin B1, cathepsin D or alkaline protease.
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PMID:Enhanced muscle protein degradation and amino acid release from the hemicorpus of acutely uremic rats. 636 19

Protein synthesis and degradation and net uptake and release of amino acids and minerals were investigated in the perfused hemicorpus of acutely uremic and sham-operated control Sprague-Dawley rats. Rats underwent bilateral nephrectomy or sham surgery and were studied 30 hours after surgery. The uremic rats displayed greater urea nitrogen appearance (net urea generation), lower plasma and muscle intracellular concentrations of most amino acids, and increased protein degradation in the hemicorpus as compared with control animals. Muscle protein synthesis was slightly but not significantly decreased in the uremic animals as compared with controls. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium, and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. Muscle ATP, creatine phosphate, and cyclic AMP, and muscle cathepsin B1, cathepsin D, and alkaline protease activities were not different in the uremic and control rats. These data provide evidence that acutely uremic rats have increased muscle protein wasting which is due to enhanced protein degradation. The cause of the increased muscle protein degradation is unknown.
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PMID:Effect of acute uremia on protein degradation and amino acid release in the rat hemicorpus. 658 68


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