title: Mechanisms of regulation of G(11)alpha protein by dexamethasone in osteoblastic UMR 106-01 cells.
abstract: We have previously demonstrated that glucocorticoids increased G(q/11)alpha protein expression and phospholipase C activity in the rat osteosarcoma cell line UMR 106-01. In this study, we demonstrated that G(11)alpha is the primary G(q)-subtype family member expressed in UMR cells. Dexamethasone treatment increased the expression of G(11)alpha protein in both a time- and a dose-dependent manner. Glucocorticoid treatment significantly increased the half-life of G(11)alpha protein from 20.3 to 63 h. Steady-state G(11)alpha mRNA level was also increased by glucocorticoid treatment by approximately 70%. This change was not the result of changes in RNA stability but rather the result of increased transcription, because the glucocorticoid-mediated upregulation of G(11)alpha mRNA was blocked by the transcription inhibitor actinomycin D. The dexamethasone induction of G(11)alpha mRNA occurred after a time lag of 12-24 h and was blocked by the protein synthesis inhibitor cycloheximide. These results suggest that the dexamethasone-induced rise in G(11)alpha protein results primarily from changes in the degradation rate of the protein, whereas changes in G(11)alpha mRNA play a smaller role and require de novo synthesis of regulatory protein(s).
authors.affiliation: Department of Pharmacology, University of Toronto, ON, Canada.
authors.forename: Ricky
authors.initials: R
authors.lastname: Cheung
authors.forename: Jane
authors.initials: J
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004355:Drug Stability; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006706:Homeostasis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D019204:GTP-Binding Proteins