Glucocorticoids induce proteasome C3 subunit expression in L6 muscle cellsby opposing the suppression of its transcription by NF-kappa B

Muscle wasting in catabolic conditions results from activation of the ubiqu itin-proteasome proteolytic pathway by a process that requires glucocortico ids and is generally associated with increased levels of mRNAs encoding com ponents of this proteolytic system. In L6 muscle cells, dexamethasone stimu lates proteolysis and increases the amount of the proteasome C3 subunit pro tein by augmenting its transcription. Transfection studies with human C3 pr omoter-luciferase reporter genes and electrophoretic mobility shift assays revealed that a NF-kappa B-protein complex containing Rel A is abundant in L6 muscle cell nuclei, Glucocorticoids stimulate C3 subunit expression by a ntagonizing the interaction of this NF-kappa B protein with an NF-kappa B r esponse element in the C3 subunit promoter region. Dexamethasone also incre ased the cytosolic amounts of the NF-kappa B p65 subunit and the I kappa B alpha inhibitor proteins in L6 cells. Incubation of L6 cells with a cytokin e mixture not only increased the amount of activated NF-kappa B but also de creased C3 promoter activity and lowered endogenous C3 subunit mRNA. Thus, NP-kappa B is a repressor of C3 proteasome subunit transcription in muscle cells, and glucocorticoids stimulate C3 subunit expression by opposing this suppressor action.