Living with a killer: the effects of hypochlorous acid on mammalian cells.
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.
Pullar
J M
JM
Pathology Department, Christchurch School of Medicine, New Zealand. juliet.pullar@chmeds.ac.nz
Vissers
M C
MC
Winterbourn
C C
CC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism / Q000633:toxicity*; D009336:Necrosis; D016877:Oxidants / Q000378:metabolism / Q000633:toxicity; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction
D016877:Oxidants; D011506:Proteins; D006997:Hypochlorous Acid; D005978:Glutathione