HIV protease inhibitor therapy reverses neutrophil apoptosis in AIDS patients by direct calpain inhibition

Apoptosis : an International Journal on Programmed Cell Death
M LichtnerLina Ghibelli

Abstract

The reduction of neutrophils apoptosis is one of the main non-virological effects of protease inhibitor (PI) therapy. We explore here whether this may be due to the cross-inhibition of calpain, an important non-virological target of PI in vitro. We found that the high basal level of neutrophils apoptosis in AIDS patients is strictly related to an increased intracellular calpain activity. Both alterations disappear after PI treatment, with apoptosis and calpain going back to normal levels after 3 months of PI therapy, independently of a proficient antiviral effect. PI drugs exerted a similar antiapoptotic and anticalpain effects on neutrophils in ex vivo experiments: strikingly, the effects were mimicked by commercially available calpain inhibitors. This study shows, for the first time, that apoptosis of neutrophils in AIDS patients is mediated by calpain, and that neutrophil survival in PI treated AIDS patients is a non virological effect due to calpain inhibition.

References

Dec 15, 1996·The Journal of Clinical Investigation·D L PitrakP Stevens
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·P AndréV Lotteau
Feb 16, 1999·Journal of Cellular Physiology·M K SquierJ J Cohen
Sep 24, 1999·Journal of Neuroscience Research·S L Chan, M P Mattson
Jan 5, 2000·Journal of Internal Medicine·H K BertholdJ K Rockstroh
Oct 7, 2000·The Journal of Infectious Diseases·C M MastroianniV Vullo
Mar 10, 2001·The Journal of Infectious Diseases·D LecossierUNKNOWN Centre de Recherche Integré sur le VIH Bichat-Claude Bernard
Oct 17, 2001·The Journal of Biological Chemistry·A GruberF Wong-Staal
Apr 20, 2002·AIDS·Marco PiccininiPier-Angelo Tovo
May 9, 2002·Biochemical Pharmacology·Wenshuai Wan, Paolo B DePetrillo
May 22, 2002·Journal of Virology·Jérôme EstaquierJacques Corbeil
Jun 14, 2002·Biochimica Et Biophysica Acta·Tao LuRonald L Mellgren
Jul 9, 2002·Apoptosis : an International Journal on Programmed Cell Death·B N PhenixA D Badley
Jul 5, 2003·Physiological Reviews·Darrell E GollJinyang Cong
Oct 14, 2003·Biochemical Pharmacology·Lina GhibelliVincenzo Vullo
Mar 12, 2005·Cell Death and Differentiation·A D Badley
Jun 24, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M D'AlessioL Ghibelli

❮ Previous
Next ❯

Citations

Jul 1, 2010·AIDS·Alba DiazUNKNOWN Study Group of Lymphoid Tissue immunopathogenesis in HIV infection
Mar 26, 2009·Retrovirology·Carole ElbimJérome Estaquier
Sep 30, 2009·Expert Opinion on Drug Metabolism & Toxicology·David James Hooker, Catherine Louise Cherry
Nov 22, 2007·Trends in Molecular Medicine·Claudio M Mastroianni, Grazia M Liuzzi
Dec 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carole ElbimJerome Estaquier
May 17, 2017·Frontiers in Cellular and Infection Microbiology·Scott D KobayashiFrank R DeLeo
Jan 24, 2020·Nature Reviews. Drug Discovery·Tamás NémethAttila Mócsai
Mar 30, 2021·Frontiers in Immunology·Morris MadzimeHelen C Steel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Related Papers

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Alberto FalchettiMaria Luisa Brandi
© 2021 Meta ULC. All rights reserved