title: Effect of rifampicin to inhibit rapamycin-induced autophagy via the suppression of protein phosphatase 2A activity.
abstract: Recently, a number of studies have focused on the secondary effects of rifampicin. In the present study, we assessed whether rifampicin influences the rapamycin-induced autophagy of RAW 264.7 cells. Here, we demonstrate that the rapamycin-induced autophagy is dependent on protein phosphatase (PP) 2A activity and rifampicin inhibits the activity of PP2A by reducing expressions of PP2A subunits A and C. In addition, rifampicin slightly, but significantly, inhibited the rapamycin-induced dephosphorylation of p70 ribosomal protein S6 kinase (p70S6K) at Thr421/Ser424, which are regulated dually by both rapamycin and PP2A, but not at the rapamycin dephosphorylation site located at Thr389. These results show that rifampicin inhibits rapamycin-induced autophagy, at least in part, via the suppression of PP2A activity.
authors.affiliation: Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Park
authors.forename: Chung Eun
authors.initials: CE
authors.lastname: Yeum
authors.forename: Gue Tae
authors.initials: GT
authors.lastname: Chae
authors.forename: Seong-Beom
authors.initials: SB
authors.lastname: Lee
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000276:immunology*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology*; D020123:Sirolimus / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D054648:Protein Phosphatase 2; D012293:Rifampin; D020123:Sirolimus