Ritonavir Inhibits NF-AT Activation Through Effects on the PI-3 Kinase/Akt Pathway

Shibani Pati,Frank Weichold,J Scott Foulke,Anhthu Nguyen,Marvin Reitz

doi:10.1186/1742-4690-2-s1-s44

Abstract

The HIV protease inhibitor ritonavir has been reported to have activities unrelated to inhibition of HIV protease, including anti-tumor activity in vivo and in vitro, induction of lipodystrophy in vivo, inhibition of the 20S proteasome, and inhibition of NFkB activation. Here we show that ritonavir also inhibits activation of NF-AT by PMA plus ionomycin and by the HHV-8 vGPCR. Inhibition of NF-AT activation occurs through the PI-3 kinase/Akt/GSK3 pathway, since ritonavir treatment leads to decreased Akt phosphorylation and a resultant decrease in GSK-3 phosphorylation. Treatment with ritonavir also inhibits the expression of NF-AT-dependent pro-inflammatory factors. Inhibition of multiple signaling pathways may help to explain the anti-tumor and other effects of ritonavir that are unrelated to its anti-retroviral activity. from 2005 International Meeting of The Institute of Human Virology Baltimore, USA, 29 August – 2 September 2005

Highlights

Ritonavir Inhibits NF-AT Activation Through Effects on the PI-3
national Meeting of The Institute of Human Virology Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here. [link 'here' using 'a href' to: http://www.biomedcentral.com/content/pdf/1742-4690-2-S1
We show that ritonavir inhibits activation of NF-AT by PMA plus ionomycin and by the HHV-8 vGPCR

Summary

Introduction

Ritonavir Inhibits NF-AT Activation Through Effects on the PI-3 Shibani Pati1, Anhthu Nguyen2, J Scott Foulke1, Frank Weichold3 and Marvin Reitz*‡1 Address: 1Institute of Human Virology, University of Maryland Biotechnology Institute, 725 W.

Results

Conclusion