Glucocorticoids Induce Proteasome C3 Subunit Expression in L6 Muscle Cells by Opposing the Suppression of Its Transcription by NF-κB

• Published in: The Journal of biological chemistry 2000-06, Vol.275 (26), p.19661-19666
• Main Authors: Du, Jie, Mitch, William E., Wang, Xiaonan, Price, S.Russ
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites; Blotting, Northern; Blotting, Western; Cells, Cultured; Cysteine Endopeptidases - biosynthesis; Cysteine Endopeptidases - genetics; Cytokines - metabolism; Cytosol - metabolism; dexamethasone; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Glucocorticoids - metabolism; Humans; Molecular Sequence Data; Multienzyme Complexes - biosynthesis; Multienzyme Complexes - genetics; Muscles - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Promoter Regions, Genetic; Proteasome Endopeptidase Complex; proteasomes; Rats; Time Factors; Transcription Factor RelA; Transcription, Genetic; Transfection; Ubiquitins - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M907258199

Muscle wasting in catabolic conditions results from activation of the ubiquitin-proteasome proteolytic pathway by a process that requires glucocorticoids and is generally associated with increased levels of mRNAs encoding components of this proteolytic system. In L6 muscle cells, dexamethasone stimulates proteolysis and increases the amount of the proteasome C3 subunit protein by augmenting its transcription. Transfection studies with human C3 promoter-luciferase reporter genes and electrophoretic mobility shift assays revealed that a NF-κB·protein complex containing Rel A is abundant in L6 muscle cell nuclei. Glucocorticoids stimulate C3 subunit expression by antagonizing the interaction of this NF-κB protein with an NF-κB response element in the C3 subunit promoter region. Dexamethasone also increased the cytosolic amounts of the NF-κB p65 subunit and the IκBα inhibitor proteins in L6 cells. Incubation of L6 cells with a cytokine mixture not only increased the amount of activated NF-κB but also decreased C3 promoter activity and lowered endogenous C3 subunit mRNA. Thus, NF-κB is a repressor of C3 proteasome subunit transcription in muscle cells, and glucocorticoids stimulate C3 subunit expression by opposing this suppressor action.