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.

Keywords:

• Rifampicin
• Autophagy
• Rapamycin
• PP2A
• RAW264.7 cells

ACKNOWLEDGMENT

This work was supported by the South Korea Science & Engineering Foundation (KOSEF) through the Cell Death Disease Research Center at the Catholic University of South Korea.