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PMID: 14636157 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Glucocorticoids regulate mRNA levels for subunits of the 19 S regulatory complex of the 26 S proteasome in fast-twitch skeletal muscles.

The Biochemical journal ·Vol. 378 ·No. Pt 1 ·2004-02-15 ·Pages 239-46

Combaret L, Taillandier D, Dardevet D, Béchet D, Rallière C, Claustre A, Grizard J, Attaix D

Abstract

Circulating levels of glucocorticoids are increased in many traumatic and muscle-wasting conditions that include insulin-dependent diabetes, acidosis, infection, and starvation. On the basis of indirect findings, it appeared that these catabolic hormones are required to stimulate Ub (ubiquitin)-proteasome-dependent proteolysis in skeletal muscles in such conditions. The present studies were performed to provide conclusive evidence for an activation of Ub-proteasome-dependent proteolysis after glucocorticoid treatment. In atrophying fast-twitch muscles from rats treated with dexamethasone for 6 days, compared with pair-fed controls, we found (i) increased MG132-inhibitable proteasome-dependent proteolysis, (ii) an enhanced rate of substrate ubiquitination, (iii) increased chymotrypsin-like proteasomal activity of the proteasome, and (iv) a co-ordinate increase in the mRNA expression of several ATPase (S4, S6, S7 and S8) and non-ATPase (S1, S5a and S14) subunits of the 19 S regulatory complex, which regulates the peptidase and the proteolytic activities of the 26 S proteasome. These studies provide conclusive evidence that glucocorticoids activate Ub-proteasome-dependent proteolysis and the first in vivo evidence for a hormonal regulation of the expression of subunits of the 19 S complex. The results suggest that adaptations in gene expression of regulatory subunits of the 19 S complex by glucocorticoids are crucial in the regulation of the 26 S muscle proteasome.

MeSH Terms
Adenosine Triphosphatases/biosynthesis,genetics Animals Chymotrypsin/metabolism Culture Techniques Cysteine Endopeptidases/biosynthesis,genetics,metabolism Cysteine Proteinase Inhibitors/pharmacology Dexamethasone/pharmacology Endopeptidases/biosynthesis,genetics Gene Expression Regulation Glucocorticoids/pharmacology Leupeptins/pharmacology Male Multienzyme Complexes/biosynthesis,genetics,metabolism Muscle Fibers, Fast-Twitch/drug effects,metabolism Muscle Proteins/metabolism Muscle, Skeletal/drug effects,metabolism Muscular Atrophy/etiology Peptide Hydrolases/biosynthesis,genetics Proteasome Endopeptidase Complex Protein Subunits/biosynthesis,genetics RNA, Messenger/metabolism Rats Rats, Wistar Ubiquitins/metabolism
Chemicals
Cysteine Proteinase Inhibitors Glucocorticoids Leupeptins Multienzyme Complexes Muscle Proteins Protein Subunits RNA, Messenger Ubiquitins Dexamethasone Endopeptidases Peptide Hydrolases Chymotrypsin Cysteine Endopeptidases Proteasome Endopeptidase Complex ATP dependent 26S protease 26S proteasome non-ATPase regulatory subunit 13 Adenosine Triphosphatases benzyloxycarbonylleucyl-leucyl-leucine aldehyde
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Combaret Lydie
Human Nutrition Research Center of Clermont-Ferrand, and Nutrition and Protein Metabolism Unit, Institut National de la Recherche Agronomique, 63122 Ceyrat, France.
Taillandier Daniel
Dardevet Dominique
Béchet Daniel
Rallière Cécile
Claustre Agnès
Grizard Jean
Attaix Didier
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
Published
2004-02-15
Pages
239-46
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1223943
Subset
IM
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