0000000000003047

AUTHOR

A. Salminen

Increased activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, enzymes of collagen biosynthesis, in skeletal muscle of endurance-trained mice.

The activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT), and the concentration of 4-hydroxyproline were measured in red and white parts of quadriceps femoris muscle of mice after 3, 10, and 20 sessions of daily endurance training. The activities of PH and GGT increased in the red part of the muscle after training for 3 and 10 times and returned to the control level after 20 training sessions. In the white muscle the increase of PH activity was less than in the red muscle. No alteration in GGT activity was observed in the white muscle. The concentration of hydroxyproline was unchanged in the both types of skeletal muscle. The results suggest that coll…

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Proteolytic capacity in mouse cardiac muscle following strenuous exercise

Proteolytic capacity in mouse cardiac muscle was analyzed 1, 3, and 6 days after exhaustive intermittent or submaximal prolonged running. No significant changes were recorded in the activities of acid or alkaline proteases, β-glucuronidase or trypsin inhibitor. Similarly, no changes were found in the rates of acid or neutral autolysis.

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Decreased level of cardiac antioxidants in endurance-trained rats.

Han-Wistar rats were exposed to a 194-200 h swimming protocol which caused a significant increase in the cardiac weight. The levels of various tissue antioxidants were assayed from the myocardium of the right ventricle and from the left ventricle (subendo- and subepimyocardium). This endurance training decreased the activities of catalase in the right ventricle and in the subendo- and subepimyocardium and Cu,Zn-superoxide dismutase in the subendomyocardium as well as the concentration of vitamin E in the right ventricle and in the subendomyocardium. Also, the activity of thioredoxin reductase decreased in each part of myocardium and that of glutathione reductase in the right ventricle and i…

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Endurance training decreases the alkaline proteolytic activity in mouse skeletal muscles.

Alkaline and myofibrillar protease activities of rectus femoris, soleus, and tibialis anterior muscles and the pooled sample of gastrocnemius and plantaris muscles were analyzed in male NMRI-mice during a running-training program of 3, 10, or 20 daily 1-h sessions. The activity of citrate synthase increased during the endurance training, reflecting the increased oxidative capacity of skeletal muscles. The activities of alkaline and myofibrillar proteases continually decreased in the course of the training program in all muscles studied. Instead, the activity of beta-glucuronidase (a marker of lysosomal hydrolases) increased in all muscles. The highest activities were observed at the beginni…

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Effects of age and prolonged running on proteolytic capacity in mouse cardiac and skeletal muscles.

Male NMRI-mice, aged 3, 6, 9, and 12 months, were made to run for a period of 4 4 at a speed of 13.5 m/min on a motor-driven treadmill, 5 days after exertion, selected enzymatic estimates of acid and alkaline proteolytic as well as energy metabolic capacities were analyzed from the cardiac muscle and from the red and white parts of m. quadriceps femoris (MQF). The activities of alkaline and myofibrillar proteases increased most considerably in skeletal muscles with age. Cathepsin D and beta-glucuronidase activities were less affected in both muscles. Prolonged running increased the activities of cathepsin D, dipeptidyl aminopeptidase I and beta-glucuronidase in the white and, especially in …

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Effects of endurance training on alkaline protease activities in rat skeletal muscles.

This study aimed at comparing the effects of running and swimming training protocols and the termination of training on the activities of two proteases with alkaline pH-optima (alkaline protease and myofibrillar protease) in the tibialis anterior, soleus, and gastrocnemius muscles of male rats. The training on treadmill decreased the activities of alkaline and myofibrillar proteases by approx. 10-20% in the muscles studied. The activities of both proteases were unchanged in swimming-trained rats. Two weeks after the termination of running training the activity of alkaline protease was increased in gastrocnemius muscle but not in the other muscles. Swimming training increased the activity of…

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X-Linked myopathy with excessive autophagy: A new hereditary muscle disease

We report on 3 brothers with a myopathy that also affected their maternal grandfather and great-uncle. Characteristic features are onset in early childhood, very slow progression, normal life expectancy, weakness of proximal limb muscles, especially in the legs, elevation of serum creatine kinase, and no cardiac or intellectual involvement. In biopsy material muscle fibers are almost never necrotic but show excessive autophagic activity and exocytosis of the phagocytosed material. We suggest that this family has an undescribed type of congenital myopathy, for which we propose the name X-linked myopathy with excessive autophagy.

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Effect of endurance training on the capacity of red and white skeletal muscle of mouse to oxidize carboxyl-14C-labelled palmitate.

Three groups of mice were trained for 1, 4 and 5 months according to different running programs on a motor driven treadmill and the fatty acid oxidation capacity (FAO) and the activities of some enzymes of energy metabolism (cytochrome c oxidase, malate dehydrogenase, triosephosphate dehydrogenase, and lactate dehydrogenase) were determined from m. quadriceps femoris (MQF). Endurance training increased the FAO [5-month training 4 days/week, 30 min/day 22% (p less than 0.05); 1-month training, 7 days/week, 150 min/day 37% (p less than 0.001); 4-month training, 5 days/week, 60 min/day 24% (p less than 0.05)]. The activities of cytochrome c oxidase and malate dehydrogenase increased approx. 30…

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Oxidative and lysosomal capacity in skeletal muscle of mice after endurance training of different intensities

The activity of certain enzymes of energy metabolism (cytochrome c oxidase, citrate synthase, malate dehydrogenase, and lactate dehydrogenase) and of lysosomes (beta-glucuronidase, beta-N-acetylglucosamindase, arylsuphatase, ribonuclease, deoxyribonuclease, acid phosphatase, and cathepsin D) was assayed from m. rectus femoris of mice trained 5 days per week, 1 hr per day for 4 weeks according to 4 different programmes: I. running speed 20 m/min, horizontal track, II. 25 m/min, horizontal track, III. 20 m/min 8 degrees uphill inclination, and IV. 25 m/min 8 degrees uphill inclination. Oxidative capacity increased and anaerobic capacity decreased without distinction between the different tran…

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Phosphomannosyl receptors of lysosomal enzymes of skeletal muscle in neuromuscular diseases.

The phosphomannosyl receptor system is responsible for both the receptor-mediated endocytosis and the intracellular transport of lysosomal enzymes. In the present study this receptor system was examined in affected muscles of patients with various neuromuscular diseases. The total activity of beta-N-acetyl-glucosaminidase, a marker enzyme of lysosomal hydrolases, was significantly elevated in the patients with myopathies (polymyositis and muscular dystrophies) but only slightly increased in those with neurogenic muscle atrophies (amyotrophic lateral sclerosis, polyneuropathy or other neurogenic muscle disease). The increase was most prominent in the group of polymyositis. The content of pho…

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Acid hydrolase activities in mouse cardiac and skeletal muscle following exhaustive exercise

Acid hydrolase activities in skeletal and cardiac muscle were studied 5, 10 and 20 days after exhaustive intermittent running by untrained and endurance-trained mice. Exhaustion increased the activities of cathepsin D, beta-glucuronidase and ribonuclease, but not that of p-nitrophenylphosphatase in skeletal muscle of untrained mice. Activities were highest on the fifth day after exhaustion and decreased during the following two weeks. More intensive loading produced no changes in acid hydrolytic capacity in skeletal muscle of endurance-trained mice. Acid hydrolase activities in cardiac muscle of both untrained and trained mice were unaffected by exhaustive running. It is suggested that exha…

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Acid hydrolase activity in red and white skeletal muscle of mice during a two-week period following exhausting exercise

The activities of beta-glucuronidase, beta-N-acetylglucosaminidase, arylsulphatase, ribonuclease, p-nitrophenylphosphatase, and malate dehydrogenase together with protein content were assayed from representative mixed (m. rectus femoris), predominantly red (proximal heads of m. vastus lateralis, m.v. medius and m. v. intermedius), and predominantly white (distal head of m. vastus lateralis) muscle homogenates of mice during a two-week period following one single exposure to exhausting intermittent running on a treadmill. The activities of cathepsin D and beta-glycerophosphatase were assayed from mixed muscle only. In all three muscle types, particularly in red muscle, the activities of beta…

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Endurance training reduces the susceptibility of mouse skeletal muscle to lipid peroxidation in vitro

Selected estimates of the lipid peroxidative capacity were assayed in the red and white skeletal muscles of control and endurance-trained mice. Endurance training decreased the lipid peroxidation rate in vitro in both muscle types. The concentration of lipids susceptible to Fe2+-induced lipid peroxidation was greater in the red than in the white skeletal muscle and increased after endurance training in the red muscle. Endurance training, however, decreased highly significantly the sensitivity of red muscle to in vitro stimulated lipid peroxidation. The activity of catalase and the concentration of vitamin E were considerably higher in the red muscle, whereas the activity of glutathione pero…

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Vitamin E deficiency and the susceptibility to lipid peroxidation of mouse cardiac and skeletal muscles

Effects of a short-term vitamin E deficiency on some lipid peroxidative properties were investigated in mouse cardiac and skeletal muscles. The concentration of vitamin E decreased 35.8% in 5 weeks and 61.2% in 12 weeks in skeletal muscle. The corresponding decrease in cardiac muscle was 65.7% in 12 weeks. Simultaneously the susceptibility of muscle homogenates to in vitro lipid peroxidation increased with 48.6% (5 weeks) and 44.5% (12 weeks) in skeletal muscle and with 101.8% (12 weeks) in cardiac muscle. Highly significant negative correlations were observed between the concentration of vitamin E and in vitro lipid peroxidation in cardiac and skeletal muscles. Also the sensitivity to Fe2+…

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Increased susceptibility to lipid peroxidation in skeletal muscles of dystrophic hamsters.

The results showed that the total content of lipids, which could be peroxidized with Fe(2 +)/ascorbate stimulation in vitro, was 45.4% and 53.7% higher than normal in the dystrophic hamster muscle at the age of 1 and 3 months, respectively. Correspondingly, the susceptibility to lipid peroxidation (stimulated by ADP-chelated iron at 37 degrees C) was 38.6-74.3% higher in dystrophic muscles. The increases were not related to necrotic lesions and inflammation observed. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, thioredoxin reductase and catalase were increased in dystrophic muscles but those of superoxide dismutases and glutathione peroxidase were unaffected.

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Food deprivation decreases the exertion-induced acid hydrolase response in mouse skeletal muscle

Strenuous prolonged running causes muscle fibre necrosis in skeletal muscles. The muscle injury is associated with inflammation and a strong increase in the total activities of certain acid hydrolases a few days after exertion. The activity changes of acid hydrolases quantitatively well reflect the severity of histopathological changes during the myopathy (for review see Salminen, Acta Physiol Scand [Suppl 539] 1985). In this study male NMRI-mice were exposed to a protocol of fasting and refeeding together with or without a 6 h run on a treadmill at 13.5 m.min-1. The animals were killed 4 days after the exercise and samples from the red part of quadriceps femoris were analyzed for arylsulfa…

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Lysosomal changes related to ageing and physical exercise in mouse cardiac and skeletal muscles.

Physical exercise increased the activities of arylsulphatase, cathepsin D and β-glucuronidase in mouse skeletal muscle but not in cardiac muscle. Exercise-induced lysosomal response was more prominent in young adult than in senescent mice. The lipofuscin content of cardiac and skeletal muscles increased markedly during ageing and was also found to increase slightly after exertion in young mice, but not in senescent ones.

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Effects of free fatty acids, lysophosphatides and phospholipase treatment on lipid peroxidation of myocardial homogenates and membrane fractions

The effects of various free fatty acids, lysophosphatides and phospholipase treatments on the enzymatic and the non-enzymatic lipid peroxidation capacities in the heart homogenates and subcellular fractions were studied. The results showed a dose related inhibition of both the enzymatic and non-enzymatic lipid peroxidation with free fatty acids. A significant inhibition occurred as early as at the concentration of 25–50 μM of several fatty acids both in homogenates and in organelle fractions. In general, the inhibition was greatest with cis-unsaturated, long-chain fatty acids. The inhibition was also induced by the pretreatment of the homogenates with phospholipase A2 but not with phospholi…

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Activities of some antioxidative and hexose monophosphate shunt enzymes of skeletal muscle in neuromuscular diseases.

The activities of some antioxidative and hexose monophosphate shunt enzymes, as well as of 2 hydrolases were studied in skeletal muscle biopsy specimens taken from 39 patients with neuromuscular diseases and from 15 controls. The activity of Se-dependent glutathione peroxidase was higher in patients with congenital myotonia, whereas in the other diagnostic groups this enzyme activity was the same as in the controls. The Se-independent and total glutathione peroxidase activity of patients in the various diagnostic groups did not differ from the controls. Moreover, no difference were observed in catalase activity between the patient groups and the controls. The activities of the rate limiting…

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Selective effects of some anesthetics and detergents on lipid peroxidation of mouse heart homogenates.

Abstract 1. 1. The effects of some anesthetics and detergents on the Fe2+/ascorbate-stimulated non-enzymatic lipid peroxidation potential and on the NADPH-dependent enzymatic lipid peroxidation capacity were characterized in mouse heart homogenates. 2. 2. Chlorpromazine turned out to be the most efficient inhibitor, causing a 50% inhibition at a concentration of 0.03 mM in the non-enzymatic assay, and at a concentration of 0.02 mM in the enzymatic assay. 3. 3. Tetracaine was about a 10-times weaker inhibitor with IC50-values of 0.25 mM. High concentration of dibucaine (1 mM) exerted a 60% inhibition in the non-enzymatic assay, but lidocaine and procaine had no prominent effect with the conc…

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Exhaustive physical exercise and acid hydrolase activity in mouse skeletal muscle

Adult, untrained NMRI mice were exhausted on a motor-driven treadmill by an intermittent-type running programme. Serial cryostate sections for the staining of NADH-tetrazolium reductase, beta-glucuronidase, beta-N-acetylglucosaminidase, and beta-glycerophosphatase activities and for making hematoxylin-eosin staining were cut from m. quadriceps femoris 1, 2, 3, 5, 7, and 15 days after physical exhaustion. A strong increase in the activities of beta-glucuronidase and beta-N-acetylglucosaminidase was observed 7 days after exhaustion and the activity changes, which were similar for the both glycosidases, were more prominent in the highly oxidative red compared to less oxidative white fibres. Ac…

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Susceptibility of mouse skeletal muscles to exercise injuries.

The susceptibility to exercise-induced myopathy was studied by histological and biochemical methods in various skeletal muscles of mice 3-4 days after a single bout of prolonged running. The degree of exercise injuries varied greatly in different muscles. Soleus and the red deep parts of quadriceps femoris were the most severely affected muscles. Extensive or scattered necrosis of muscle fibers was associated with focal inflammation and a five- to nine-fold increase in the activity of beta-glucuronidase in these muscles. Slight necrotic changes and a two- to three-fold increase in the activity of beta-glucuronidase were observed in tibialis anterior, plantaris, and the red deep parts of gas…

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Acid proteolytic capacity in mouse cardiac and skeletal muscles after prolonged submaximal exercise

Acid proteolytic capacity in mouse cardiac muscle and in predominantly white (distal head of m. vastus lateralis) or predominantly red (proximal red heads of m. vastus lateralis, m. v. medialis, and m. v. intermedius) skeletal muscle was estimated 5 days after 3 h, 6 h or 9 h prolonged running at a speed of 13.5 m/min. The activities of acid protease and beta-glucuronidase together with the rate of acid autolysis considerably increased in both skeletal muscle types, especially in red muscle, but did not increase in cardiac muscle. Acid proteolytic capacity and beta-glucuronidase activity increased in relation to the duration of running. Protein content and oxidative capacity (the activities…

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Collagen metabolism of mouse skeletal muscle during the repair of exercise injuries.

The activities of prolyl 4-hydroxylase and beta-glucuronidase, the concentration of hydroxyproline as well as reticulin and collagen type III, IV and V stainings were followed in skeletal muscle during a 20-day period after a 9-h treadmill running in untrained and trained male mice, aged 4-6 months. The prolonged 9-h running of untrained mice temporarily increased prolyl 4-hydroxylase activity 2, 5 and 10 days after exercise, more prominently in the red than in the white part of quadriceps femoris-muscle, and in analogical manner as beta-glucuronidase activity in tibialis anterior-muscle. Twenty days after exercise these enzymatic activities were back to the control level. The hydroxyprolin…

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Prednisolone decreases exercise-induced acid hydrolase response in mouse skeletal muscle.

Male NMRI-mice were subjected to exhaustive treadmill exercise. 3 and 6 days after the exertion, quadriceps femoris muscles were examined histologically and analyzed for acid hydrolases in order to follow the degree and progress of injuries. Prednisolone (PRED), an anti-inflammatory corticosteroid, was given to some of the animals in order to modify the exercise response. The PRED administration began 14 h before exercise and continued until the end of the experiment (6 days). The doses were 25 and 50 mg . kg-1 i.p. twice a day. The activities of both arylsulphatase and beta-glucuronidase increased significantly in the exercise control group after 3 and 6 days. The increase in activity corr…

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Lysosomal changes related to exercise injuries and training-induced protection in mouse skeletal muscle

Three experiments were designed to study the lysosomal changes associated with the development and maintenance of the endurance training induced resistance against exercise injuries in mouse skeletal muscles. The activities of arylsulphatase, cathepsin C, cathepsin D, and beta-glucuronidase were assayed from the red part of mouse quadriceps femoris muscle 4 days after prolonged strenuous running of 4-9 h duration. Exercise injuries were characterized by necrotic fibers and focal inflammation. Strenuous running of untrained mice induced necrotic lesions and a 4-5 fold increase in the activities of lysosomal enzymes. This lysosomal response was considerably reduced already by daily training b…

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Endurance training and antioxidants of lung

Mice and rats were adjusted to daily treadmill training programs, which were heavy enough to increase the oxidative capacity of skeletal muscles. Endurance training did not affect the activities of catalase and glutathione peroxidase and the concentration of vitamin E in the lungs of mice and rats. Thus increased ventilation and oxygen utilization induced by exercise training do not modify lung antioxidants, in contrast to hyperoxia and hypoxia.

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Characteristics of lysosomal phosphomannosyl-enzyme receptors in the rat heart

The receptor system recognizing mannose 6-phosphate groups of lysosomal enzymes has been characterized, e.g. in fibroblasts and liver cells. The purpose of this study was to demonstrate the presence of a phosphomannosyl receptor system in rat heart muscle. The characterization of receptors was accomplished with beta-N-acetylglucosaminidase (beta-GA) secreted by rat embryo fibroblasts after ammonium chloride stimulation. The receptor binding of ligand enzymes was saturated by adding increasing concentrations of beta-GA and the binding increased linearly when the content of membrane protein was increased. The binding of beta-GA was inhibited by mannose and glucose phosphates, especially manno…

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Lysosomal changes in mouse skeletal muscle during the repair of exercise injuries

Lysosomal changes of mouse skeletal muscle during the repair of exercise injuries were studied with biochemical, histochemical, and electron microscopic methods. Treadmill running for 4 hours and 9 hours increased the activities of cathepsin C and beta-glucuronidase, but not that of beta-glycerophosphatase in mouse quadriceps femoris muscle. The highest activities occurred 3 days after exertion and were higher after the longer duration of exertion. Similar changes that were highly correlated with the activities of lysosomal enzymes occurred in the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and in the concentration of DNA. The activities of lysosomal…

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Chronic hydrogen peroxide intake and peroxide metabolizing enzyme activities in some tissues of mice and rats

Chronic daily intake of 0.5% H2O2 in drinking water decreased Se-dependent glutathione peroxidase (Se-GSHPx) activity in rat skeletal muscle, kidney and liver. Non-Se GSHPx activity decreased in kidney. Deprivation of drinking water decreased Se-GSHPx activity in kidney and non-Se GSHPx activity in kidney and liver. H2O2 intake decreased activity of catalase in rat skeletal muscle. H2O2 intake or water deprivation caused no changes in these enzyme activities in mice.

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