Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein delivery from genetically modified skeletal muscle has been reported previously. However, a stable and prolonged secretion was obtained in immunocompromised or newborn animals only. To evaluate the clinical relevance of this approach, we have transduced myoblasts from an adult beta-glucuronidase-deficient (MPS VII) mouse with retroviral vectors carrying either the human beta-glucuronidase cDNA or the murine erythropoietin (Epo) cDNA. The cells were then grafted into the tibialis anterior muscle of adult immunocompetent MPS VII recipients. Protein expression was controlled either by ubiquitous or muscle-specific transcriptional regulatory elements. Animals were analyzed over an 8-month period. The in situ detection of beta-glucuronidase activity revealed up to 60% of genetically modified myofibers in the recipient muscles. The human desmin promoter and enhancer showed the highest in vivo expression. Secretion of beta-glucuronidase induced a disappearance of lysosomal storage lesions in the liver and spleen of recipient animals. Delivery of Epo led to a permanent increase of hematocrit values over 3 months. These results showed that the transplantation of genetically modified myoblasts allowed a sustained secretion of recombinant proteins at therapeutic levels in immunocompetent adult mice. They suggest that the approach may be considered for human applications.
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PMID:Long-term secretion of therapeutic proteins from genetically modified skeletal muscles. 882 64

Specific antibodies against structural proteins of muscle fibres (actin, desmin, dystrophin) and extracellular matrix (fibronectin) were used to study the effect of eccentrically biased downhill running exercise (13,5 degrees, 17 m min(-1), 130 min) on the magnitude and properties of myofibre injury in the quadriceps femoris muscle of male and female rats. Muscle beta-glucuronidase activity, a quantitative indicator of muscle damage, showed clearly smaller increase in female than in male rats during the 4-day period following exercise. A similar course of histopathological changes was observed in both sexes, although females showed slower and less marked changes than males. In males, discontinuous or even lost submembrane protein dystrophin staining was observed in some swollen fibres immediately after exercise, before the loss of desmin and staining of disorganized actin, i.e. before the disruption of the cytoskeletal system and the contractile apparatus. The observation that no dramatic changes in the microarchitecture of the muscle fibres were detected immediately or even 6 h after the exercise in females compared with males may indicate that the sarcolemma of the females might be strengthened against membrane damage by a still unknown stabilizing compound.
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PMID:Gender differences in skeletal muscle fibre damage after eccentrically biased downhill running in rats. 1007 98

To study the hypothesis that more severe damage, caused by controlled lengthening (L) contractions, results in greater myofiber hypertrophy compared to increase in fiber size followed shortening (S) contractions, tibialis anterior muscles of anesthesized male Wistar rats were subjected to 240 either L or S contractions. The highest increase in muscle beta-glucuronidase activity, an indicator of muscle damage, was observed in L (7.1-fold) 4 days and in S (2.6-fold) 8 days postexercise. Dystrophin- and desmin-negative as well as fibronectin-positive fibers (signs of the early phase of damage) were observed immediately after exercise in the L group. At 4 days, massive myofiber injury was visible, and internally localized nuclei were present at 15-80 days after exercise in the L group. The shift towards more glycolytic fiber types (p<0.05 in L and S) and an increased mean cross-sectional area of type IIX/B fibers (p < 0.001 in L and S) at 80 days were observed in both groups. The observed minor damage with unchanged myofiber structures following S induced, however, an increase in myofiber cross-sectional area of nearly the same magnitude as that following L, which was more damaging. The results do not support the hypothesis that fiber hypertrophy depends on the extent of the myofiber damage upon the exercised muscles.
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PMID:Controlled lengthening or shortening contraction-induced damage is followed by fiber hypertrophy in rat skeletal muscle. 1072 70

The aim of this study was to evaluate the effect of repeated bouts of exercise on the cytoskeletal proteins titin, desmin, and dystrophin. Rats were made to run downhill for 90 min 1 or 5 times separated by 14 days. Samples were taken from quadriceps femoris muscle 3, 48, 96 h and 50 days after the last exercise session and detected by quantitative PCR, histochemical stainings, and western blot analyses. Histopathological changes in titin, desmin, and dystophin stainings, an increase in beta-glucuronidase activity (a quantitative indicator of muscle damage), a significant decrease in the relative content of dystrophin, and intramyocellular Evans blue staining (signs of changes in sarcolemmal permeability) observed after one exercise session were attenuated after 5 exercise sessions. Titin mRNA level was not increased after the initial exercise session but was increased after the fifth session. Desmin and dystrophin mRNA levels were increased after the first and fifth sessions with desmin showing a smaller increase after the fifth session compared to the first session. Prior exercise induces adaptation that protects the sarcolemma as well as subsarcolemmal, intermediate filament, and sarcomeric proteins against disruption. Changes in mRNA levels of titin, desmin, and dystophin after an acute exercise session obviously reflect the need of these proteins in the repair process following damage. After five sessions increase in mRNA of studied proteins suggest a strong involvement in continuing adaptation to the increased exercise.
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PMID:Repeated bout effect on the cytoskeletal proteins titin, desmin, and dystrophin in rat skeletal muscle. 1743 58