Abstract
The production of hypochlorous acid (HOCl) by the myeloperoxidase-H2O2-Cl- system of phagocytes plays a vital role in the ability of these cells to kill a wide range of pathogens. However, the generation of a potent oxidant is not without risk to the host, and there is evidence that HOCl contributes to the tissue injury associated with inflammation. In this review, we discuss the biological reactivity of HOCl, and detail what is known of how it interacts with mammalian cells. The outcome of exposure is dependent on the dose of oxidant, with higher doses causing necrosis, and apoptosis or growth arrest occurring with lower amounts. Glutathione (GSH) and protein thiols are easily oxidized, and are preferred targets with low, sublethal amounts of HOCl. Thiol enzymes vary in their sensitivity to HOCl, with glyceraldehyde-3-phosphate dehydrogenase being most susceptible. Indeed, loss of activity occurred before GSH oxidation. The products of these reactions and the ability of cells to regenerate oxidized thiols are discussed. Recent reports have indicated that HOCl can activate cell signaling pathways, and these studies may provide important information on the role of this oxidant in inflammation.
Citations
Apr 7, 2004·Mutation Research·Ilya B ZavodnikRussel J Reiter
Apr 30, 2002·Free Radical Biology & Medicine·I Dalle-DonneA Milzani
Oct 4, 2002·Free Radical Biology & Medicine·John J Haddad
Nov 11, 2003·Free Radical Biology & Medicine·Alexander V Peskin, Christine C Winterbourn
Apr 22, 2010·The Journal of Biological Chemistry·Sandra E Gomez-MejibaDario C Ramirez
Sep 2, 2011·The Journal of Biological Chemistry·Anna-Karin TidénAnthony J Kettle
Jan 12, 2013·The Journal of Biological Chemistry·Anna L P ChapmanAnthony J Kettle
Aug 25, 2011·Antioxidants & Redox Signaling·David M BoothDavid N Criddle
May 8, 2007·Applied and Environmental Microbiology·Geun Woo ParkMark D Sobsey
Dec 2, 2011·PloS One·Carlos Eduardo A SouzaHusam M Abu-Soud
Jul 11, 2013·PloS One·Cornelia SpethBeate E Kehrel
Nov 14, 2013·PloS One·Zoltán NoszticziusJános Szegedi
Sep 28, 2012·Marine Drugs·Eliseu RodriguesAdriana Z Mercadante
Sep 26, 2013·European Journal of Nutrition·A C MorandiR Otton
Nov 7, 2014·PloS One·Dhiman MaitraHusam M Abu-Soud
Oct 20, 2011·Biochimica Et Biophysica Acta·Ya-ting Tina YangSteven P Gieseg
Apr 5, 2012·Life Sciences·Ya-ting Tina YangSteven P Gieseg
Oct 15, 2013·Free Radical Biology & Medicine·Mitchell M LloydClare L Hawkins
Jul 10, 2010·Free Radical Biology & Medicine·Stephanie M BozonetMargreet C M Vissers
Sep 24, 2008·Journal of Dental Research·M T Ashby
Mar 30, 2019·Advanced Materials·Chi ZhangXian-Zheng Zhang
Aug 15, 2019·Journal of Leukocyte Biology·Usharani TallaMargreet C M Vissers
Aug 30, 2019·PLoS Biology·Arden PerkinsKaren Guillemin
Jul 25, 2019·Journal of Bacteriology·Elizabeth A WalkerBlythe E Janowiak
Apr 7, 2020·Journal of Applied Microbiology·H M ZmudaH Beyenal
Sep 27, 2020·Indoor Air·Yeonjeong HaJung-Hwan Kwon
Mar 12, 2015·Acta Physiologica·V CsatóZ Papp
Sep 1, 2021·Environmental Science & Technology·Douglas B Collins, Delphine K Farmer
Nov 6, 2021·Frontiers in Immunology·Demba SarrJulie M Moore