Peroxynitrite mediates calcium-dependent mitochondrial dysfunction and cell death via activation of calpains

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Matthew WhitemanBarry Halliwell

Abstract

Chondrocyte cell death is a hallmark of inflammatory and degenerative joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA), but the molecular and cellular mechanisms involved have yet to be elucidated. Because 3-nitrotyrosine, a marker for reactive nitrogen species such as peroxynitrite, has been observed in OA and RA cartilage and has been associated with chondrocyte cell death, we investigated the mechanisms by which peroxynitrite induces cell death in human articular chondrocytes. The earliest biochemical event observed, subsequent to treatment with either peroxynitrite or the peroxynitrite generator SIN-1, was a rapid rise in intracellular calcium that lead to mitochondrial dysfunction and cell death. Although, chondrocyte death exhibited several classical hallmarks of apoptosis, including annexin V labeling, increased fraction of cells with subG1 DNA content and DNA condensation, we did not find evidence for caspase involvement either by Western blotting, fluorimetric assays, or caspase inhibition. Additionally, peroxynitrite did not inhibit cellular caspase activity. Furthermore, using other established assays of cell viability, including the MTT assay and release of lactate dehydrogenase, we found tha...Continue Reading

References

Nov 1, 1992·Arthritis and Rheumatism·S YamamotoT Yamamuro
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J S BeckmanB A Freeman
Jan 1, 1989·Journal of Cardiovascular Pharmacology·M FeelischE Noack
Sep 1, 1988·The American Journal of Physiology·T E GunterK K Gunter
Feb 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·L V JohnsonL B Chen
Jun 1, 1995·Annals of the Rheumatic Diseases·B Halliwell
Jul 17, 1995·Biochimica Et Biophysica Acta·M Zoratti, I Szabò
May 1, 1994·Journal of Cellular Physiology·M K SquìerJ J Cohen
Jan 1, 1993·Free Radical Research Communications·R E Huie, S Padmaja
Jan 1, 1997·Free Radical Biology & Medicine·S PfeifferB Mayer
Aug 1, 1997·Nitric Oxide : Biology and Chemistry·J HaendelerS Dimmeler
Jun 25, 1998·The Journal of Cell Biology·S TanD Schubert
Jun 26, 1998·Free Radical Biology & Medicine·D Jang, G A Murrell
Jul 22, 1998·Chemical Research in Toxicology·R Radi
Aug 4, 1998·General Pharmacology·M P MurphyS W Martin
Aug 12, 1998·BioFactors·J C Fernández-ChecaE Ardite
Dec 31, 1998·Free Radical Biology & Medicine·L VirágC Szabó
Jul 27, 1999·Osteoarthritis and Cartilage·R StuderC H Evans
Jul 27, 2000·American Journal of Physiology. Cell Physiology·S Zhuang, G Simon
Jul 29, 2000·Methods in Enzymology·Z Darzynkiewicz, E Bedner
Jul 29, 2000·Methods in Enzymology·H R Stennicke, G S Salvesen
Sep 20, 2000·Leukemia·D E Johnson
Oct 4, 2000·Neurobiology of Aging·K SchindowskiA Eckert
Dec 7, 2000·The American Journal of Pathology·S CuzzocreaC Thiemermann
Apr 27, 2001·FEBS Letters·A J KowaltowskiA E Vercesi
Jun 9, 2001·Methods in Cell Biology·D L Mykles
Jul 24, 2001·Arthritis and Rheumatism·P I MappD R Blake

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Citations

Jun 28, 2008·Apoptosis : an International Journal on Programmed Cell Death·Paula M BritoTeresa C P Dinis
Oct 21, 2005·American Journal of Physiology. Cell Physiology·Marcello DelCarlo, Richard F Loeser
Jan 24, 2007·Physiological Reviews·Pál PacherLucas Liaudet
Jun 6, 2012·Neurology Research International·Raul Chavez-ValdezFrances J Northington
Feb 10, 2011·BMC Musculoskeletal Disorders·Berta Cillero-PastorFrancisco J Blanco
May 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jeremy HerzogEmil R Unanue
Mar 5, 2014·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Tzvetanka Bondeva, Gunter Wolf
Apr 18, 2007·Current Rheumatology Reports·Jose U ScherSteven B Abramson
Jan 16, 2016·Biochimica Et Biophysica Acta·Panagiotis Lepetsos, Athanasios G Papavassiliou
Feb 18, 2016·Oxidative Medicine and Cellular Longevity·Subrata Kumar Biswas
Mar 17, 2009·European Journal of Pharmacology·Bahareh Tavakoli-FarMassoud Mahmoudian
Apr 15, 2008·Biochemical and Biophysical Research Communications·Matthew Whiteman, Jeremy P E Spencer
Jun 12, 2008·British Journal of Haematology·Ian DanielsAndrew P Haynes
Mar 27, 2009·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Zhong L JiangGhassan M Saed
Jun 10, 2014·Lasers in Surgery and Medicine·Klára BarabásZoltán Szekanecz
Apr 8, 2006·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Po-Lin KuoChun-Ching Lin
Oct 17, 2015·Arthritis & Rheumatology·Mitchell C ColemanJames A Martin
Nov 22, 2005·Biochemical and Biophysical Research Communications·Matthew WhitemanJeffrey S Armstrong
Sep 18, 2012·Free Radical Biology & Medicine·Ghassan J MaghzalVincent Jaquet
Oct 1, 2008·Osteoarthritis and Cartilage·Steven B Abramson
Dec 22, 2016·International Journal of Molecular Sciences·Edith CharlierDominique De Seny
Nov 4, 2015·International Journal of Molecular Sciences·Hyun Sook Hwang, Hyun Ah Kim
Aug 2, 2007·Nature Reviews. Drug Discovery·Csaba SzabóRafael Radi
Jul 4, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yong-Jie ZhangJian-Zhi Wang
Jan 5, 2011·Nature Reviews. Rheumatology·Francisco J BlancoCristina Ruiz-Romero
Jun 27, 2009·Immunopharmacology and Immunotoxicology·Rizwan AhmadHaseeb Ahsan
Feb 6, 2020·Journal of Cellular Physiology·Nashrah AhmadTariq M Haqqi

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