Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.cellsig.2006.08.019
Title: The pro-inflammatory oxidant hypochlorous acid induces Bax-dependent mitochondrial permeabilisation and cell death through AIF-/EndoG-dependent pathways
Authors: Whiteman, M. 
Chu, S.H.
Siau, J.L.
Rose, P. 
Sabapathy, K.
Cheung, N.S. 
Armstrong, J.S. 
Schantz, J.-T. 
Spencer, J.P.E.
Keywords: Arthritis
Bax
Cell death
Hypochlorous acid
Mitochondria
Oxidative stress
Issue Date: 2007
Source: Whiteman, M., Chu, S.H., Siau, J.L., Rose, P., Sabapathy, K., Cheung, N.S., Armstrong, J.S., Schantz, J.-T., Spencer, J.P.E. (2007). The pro-inflammatory oxidant hypochlorous acid induces Bax-dependent mitochondrial permeabilisation and cell death through AIF-/EndoG-dependent pathways. Cellular Signalling 19 (4) : 705-714. ScholarBank@NUS Repository. https://doi.org/10.1016/j.cellsig.2006.08.019
Abstract: At sites of chronic inflammation, such as in the inflamed rheumatoid joint, activated neutrophils release hydrogen peroxide (H2O2) and the enzyme myeloperoxidase to catalyse the formation of hypochlorous acid (HOCl). 3-chlorotyrosine, a marker of HOCl in vivo, has been observed in synovial fluid proteins from rheumatoid arthritis patients. However the mechanisms of HOCl-induced cytotxicity are unknown. We determined the molecular mechanisms by which HOCl induced cell death in human mesenchymal progenitor cells (MPCs) differentiated into a chondrocytic phenotype as a model of human cartilage cells and show that HOCl induced rapid Bax conformational change, mitochondrial permeability and release of intra-mitochondrial pro-apoptotic proteins which resulted in nuclear translocation of AIF and EndoG. siRNA-mediated knockdown of Bax substantially prevented mitochondrial permeability, release of intra-mitochondrial pro-apoptotic proteins. Cell death was inhibited by siRNA-mediated knockdown of Bax, AIF or EndoG. Although we observed several biochemical markers of apoptosis, caspase activation was not detected either by western blotting, fluorescence activity assays or by using caspase inhibitors to inhibit cell death. This was further supported by findings that (1) in vitro exposure of recombinant human caspases to HOCl caused significant inhibition of caspase activity and (2) the addition of HOCl to staurosporine-treated MPCs inhibited the activity of cellular caspases. Our results show for the first time that HOCl induced Bax-dependent mitochondrial permeability which led to cell death without caspase activity by processes involving AIF/EndoG-dependent pathways. Our study provides a novel insight into the potential mechanisms of cell death in the inflamed human joint. © 2006 Elsevier Inc. All rights reserved.
Source Title: Cellular Signalling
URI: http://scholarbank.nus.edu.sg/handle/10635/28941
ISSN: 08986568
DOI: 10.1016/j.cellsig.2006.08.019
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

38
checked on Dec 13, 2017

WEB OF SCIENCETM
Citations

34
checked on Dec 13, 2017

Page view(s)

212
checked on Dec 9, 2017

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.