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)

The effect of dexamethasone on protein degradation and the involvement of different proteolytic pathways were examined in cultured L6 myotubes. Treatment of the cells with dexamethasone resulted in an approximately 20% increase in protein degradation at a hormone concentration of 10(-7) to 10(-6) M. By using various proteolytic blockers, evidence was found that the dexamethasone-induced increase in protein breakdown mainly reflected energy-proteasome-dependent proteolysis and to a lesser extent calcium-dependent protein breakdown. In contrast, the hormone treatment did not increase lysosomal proteolysis. mRNA levels for cathepsin B, ubiquitin, and the proteasome subunit C3 were increased by dexamethasone. The results suggest that glucocorticoids stimulate calcium and energy-proteasome-dependent muscle proteolysis and that changes in mRNA levels for proteolytic enzymes do not necessarily reflect the involvement of different proteolytic pathways.
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PMID:Dexamethasone stimulates proteasome- and calcium-dependent proteolysis in cultured L6 myotubes. 978 63

The ubiquitin-proteasome proteolytic system is stimulated in conditions causing muscle atrophy. Signals initiating this response in these conditions are unknown, although glucocorticoids are required but insufficient to stimulate muscle proteolysis in starvation, acidosis, and sepsis. To identify signals that activate this system, we studied acutely diabetic rats that had metabolic acidosis and increased corticosterone production. Protein degradation was increased 52% (P < 0.05), and mRNA levels encoding ubiquitin-proteasome system components, including the ubiquitin-conjugating enzyme E214k, were higher (transcription of the ubiquitin and proteasome subunit C3 genes in muscle was increased by nuclear run-off assay). In diabetic rats, prevention of acidemia by oral NaHCO3 did not eliminate muscle proteolysis. Adrenalectomy blocked accelerated proteolysis and the rise in pathway mRNAs; both responses were restored by administration of a physiological dose of glucocorticoids to adrenalectomized, diabetic rats. Finally, treating diabetic rats with insulin for >/=24 h reversed muscle proteolysis and returned pathway mRNAs to control levels. Thus acidification is not necessary for these responses, but glucocorticoids and a low insulin level in tandem activate the ubiquitin-proteasome proteolytic system.
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PMID:Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. 1032 62