No alteration in gene expression of components of the ubiquitin-proteasome proteolytic pathway in dystrophin-deficient muscles.
Increased expression of critical components of the ubiquitin-dependent proteolytic pathway occurs in any muscle wasting condition so far studied in rodents where proteolysis rises. We have recently reported similar adaptations in head trauma patients [Mansoor et al. (1996) Proc. Natl. Acad. Sci. USA 93, 2714-2718]. We demonstrate here that the increased muscle protein breakdown seen in mdx mice only correlated with enhanced expression of m-calpain, a Ca(2+)-activated proteinase. By contrast, no change in mRNA levels for components of the ubiquitin-proteasome proteolytic process was seen in muscles from both mdx mice and Duchenne muscular dystrophy patients. Thus, gene expression of components of this pathway is not regulated in the chronic wasting that characterizes muscular dystrophy.
Combaret
L
L
Centre de Recherche en Nutrition Humaine de Clermont-Ferrand, Unité d'Etude du Métabolisme Azote, Ceyrat, France.
Taillandier
D
D
Voisin
L
L
Samuels
S E
SE
Boespflug-Tanguy
O
O
Attaix
D
D
D000293:Adolescent; D000818:Animals; D002154:Calpain / Q000096:biosynthesis; D002402:Cathepsin D / Q000096:biosynthesis; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis; D002648:Child; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D016189:Dystrophin / Q000172:deficiency*; D010450:Endopeptidases; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D014158:Transcription, Genetic; D014452:Ubiquitins / Q000096:biosynthesis* / Q000235:genetics
D016189:Dystrophin; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014452:Ubiquitins; D002403:Cathepsins; D010450:Endopeptidases; D002154:Calpain; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D002402:Cathepsin D; D046988:Proteasome Endopeptidase Complex