Principal Investigator, Centre for Free Radical Research
Research Professor
BSc(Hons) PhD(Otago) MSc(SFU) FRSNZ
Email tony.kettle@otago.ac.nz
Tel +64 3 364 0577
Research interests
For the past 25 years, we have probed the enzymology of myeloperoxidase (MPO). This haem protein gives pus and phlegm their characteristic green tinge. MPO produces chlorine bleach from hydrogen peroxide and common salt.
The knowledge from this work has helped us understand how white blood cells called neutrophils use MPO to kill bacteria. It has also revealed that chlorine bleach and free radicals contribute to inflammation.
We have shown that chlorine bleach promotes inflammatory tissue damage in cystic fibrosis, asthma, rheumatoid arthritis, and cardiovascular disease. In collaboration with AstraZeneca, we have also developed specific inhibitors of MPO that are potential anti-inflammatory drugs.
Current research topics
Cystic Fibrosis  | Heart Disease  | Neutrophils  |
Radical Reactions  | Myeloperoxidase  | Biomarkers  |
Public Health Lectures
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In the media
Professor Kettle was interviewed for Radio New Zealand's Our Changing World series in October 2014.
Publications
Tidén, A.-K., Sjögren, T., Svensson, M., Bernlind, A., Senthilmohan, R., Auchère, F., … Forbes, L. V., Magon, N. J., Paton, L. N., Jameson, G. N. L., … Kettle, A. J. (2011). 2-Thioxanthines are mechanism-based inactivators of myeloperoxidase that block oxidative stress during inflammation. Journal of Biological Chemistry, 286(43), 37578-37589. doi: 10.1074/jbc.M111.266981
Winterbourn, C. C., Hampton, M. B., Livesey, J. H., & Kettle, A. J. (2006). Modeling the reactions of superoxide and myeloperoxidase in the neutrophil phagosome: Implications for microbial killing. Journal of Biological Chemistry, 281(52), 39860-39869.
Meotti, F. C., Jameson, G. N. L., Turner, R., Harwood, D. T., Stockwell, S., Rees, M., … Kettle, A. J. (2011). Urate as a physiological substrate for myeloperoxidase: Implications for hyperuricemia and inflammation. Journal of Biological Chemistry, 286(15), 12901-12911. doi: 10.1074/jbc.M110.172460
Kettle, A. J., Anderson, R. F., Hampton, M. B., & Winterbourn, C. C. (2007). Reactions of superoxide with myeloperoxidase. Biochemistry, 46, 4888-4897.
Parker, H., Albrett, A. M., Kettle, A. J., & Winterbourn, C. C. (2012). Myeloperoxidase associated with neutrophil extracellular traps is active and mediates bacterial killing in the presence of hydrogen peroxide. Journal of Leukocyte Biology, 91(3), 369-376. doi: 10.1189/jlb.0711387
Journal - Research Article
Parker, H., Albrett, A. M., Kettle, A. J., & Winterbourn, C. C. (2012). Myeloperoxidase associated with neutrophil extracellular traps is active and mediates bacterial killing in the presence of hydrogen peroxide. Journal of Leukocyte Biology, 91(3), 369-376. doi: 10.1189/jlb.0711387
Moya-Olano, L., Milne, H. M., Robinson, J. M., Hill, J. V., Frampton, C. M., Abbott, H. F., Turner, R., Kettle, A. J., & Endre, Z. H. (2011). Trientine and renin-angiotensin system blockade ameliorate progression of glomerular morphology in hypertensive experimental diabetic nephropathy. Pathology International, 61(11), 652-661. doi: 10.1111/j.1440-1827.2011.02721.x
Kettle, A. J., Maroz, A., Woodroffe, G., Winterbourn, C. C., & Anderson, R. F. (2011). Spectral and kinetic evidence for reaction of superoxide with compound I of myeloperoxidase. Free Radical Biology & Medicine, 51(12), 2190-2194. doi: 10.1016/j.freeradbiomed.2011.09.019
Tidén, A.-K., Sjögren, T., Svensson, M., Bernlind, A., Senthilmohan, R., Auchère, F., … Forbes, L. V., Magon, N. J., Paton, L. N., Jameson, G. N. L., … Kettle, A. J. (2011). 2-Thioxanthines are mechanism-based inactivators of myeloperoxidase that block oxidative stress during inflammation. Journal of Biological Chemistry, 286(43), 37578-37589. doi: 10.1074/jbc.M111.266981
Meotti, F. C., Jameson, G. N. L., Turner, R., Harwood, D. T., Stockwell, S., Rees, M., … Kettle, A. J. (2011). Urate as a physiological substrate for myeloperoxidase: Implications for hyperuricemia and inflammation. Journal of Biological Chemistry, 286(15), 12901-12911. doi: 10.1074/jbc.M110.172460
Marshall, C. J., Nallaratnam, M., Mocatta, T., Smyth, D., Richards, M., Elliott, J. M., Blake, J., Winterbourn, C. C., Kettle, A. J., & McClean, D. R. (2010). Factors influencing local and systemic levels of plasma myeloperoxidase in ST-segment elevation acute myocardial infarction. American Journal of Cardiology, 106(3), 316-322. doi: 10.1016/j.amjcard.2010.03.028
Nagy, P., Kettle, A. J., & Winterbourn, C. C. (2010). Neutrophil-mediated oxidation of enkephalins via myeloperoxidase-dependent addition of superoxide. Free Radical Biology & Medicine, 49, 792-799. doi: 10.1016/j.freeradbiomed.2010.05.033
Das, A. B., Nagy, P., Abbott, H. F., Winterbourn, C. C., & Kettle, A. J. (2010). Reactions of superoxide with the myoglobin tyrosyl radical. Free Radical Biology & Medicine, 48, 1540-1547. doi: 10.1016/j.freeradbiomed.2010.02.039
Thomson, E., Brennan, S., Senthilmohan, R., Gangell, C. L., Chapman, A. L., Sly, P., & Kettle, A. J. (2010). Identifying peroxidases and their oxidants in the early pathology of cystic fibrosis. Free Radical Biology & Medicine, 49(9), 1354-1360. doi: 10.1016/j.freeradbiomed.2010.07.010
Koelsch, M., Mallak, R., Graham, G. G., Kajer, T., Milligan, M. K., Nguyen, L. Q., … Kettle, A. J., … Davies, M. J. (2010). Acetaminophen (paracetamol) inhibits myeloperoxidase-catalyzed oxidant production and biological damage at therapeutically achievable concentrations. Biochemical Pharmacology, 79, 1156-1164. doi: 10.1016/j.bcp.2009.11.024
Ximenes, V. F., Maghzal, G. J., Turner, R., Kato, Y., Winterbourn, C. C., & Kettle, A. J. (2010). Serotonin as a physiological substrate for myeloperoxidase and its superoxide-dependent oxidation to cytotoxic tryptamine-4,5-dione. Biochemical Journal, 425(1), 285-293. doi: 10.1042/BJ20090776
Harwood, D. T., Kettle, A. J., Brennan, S., & Winterbourn, C. C. (2009). Simultaneous determination of reduced glutathione, glutathione disulphide and glutathione sulphonamide in cells and physiological fluids by isotope dilution liquid chromatography-tandem mass spectrometry. Journal of Chromatography B, 877, 3393-3399. doi: 10.1016/j.jchromb.2009.04.018
Peskin, A. V., Turner, R., Maghzal, G. J., Winterbourn, C. C., & Kettle, A. J. (2009). Oxidation of methionine to dehydromethionine by reactive halogen species generated by neutrophils. Biochemistry, 48(42), 10175-10182. doi: 10.1021/bi901266w
Nagy, P., Kettle, A. J., & Winterbourn, C. C. (2009). Superoxide-mediated formation of tyrosine hydroperoxides and methionine sulfoxide in peptides through radical addition and intramolecular oxygen transfer. Journal of Biological Chemistry, 284(22), 14723-14733. doi: 10.1074/jbc.M809396200
Chapman, A. L. P., Skaff, O., Senthilmohan, R., Kettle, A. J., & Davies, M. J. (2009). Hypobromous acid and bromamine production by neutrophils and modulation by superoxide. Biochemical Journal, 417(3), 773-781. doi: 10.1042/BJ20071563
van Dalen, C. J., Aldridge, R. E., Chan, T., Senthilmohan, R., Hancox, R. J., Cowan, J. O., Taylor, D. R., Town, G. I., & Kettle, A. J. (2009). Bromotyrosines in sputum proteins and treatment effects of terbutaline and budesonide in asthma. Annals of Allergy, Asthma, & Immunology, 103(4), 348-353.
Coker, M. S. A., Hu, W.-P., Senthilmohan, S. T., & Kettle, A. J. (2008). Pathways for the decay of organic dichloramines and liberation of antimicrobial chloramine gases. Chemical Research in Toxicology, 21(12), 2334-2343. doi: 10.1021/tx800232v
Meotti, F. C., Senthilmohan, R., Harwood, D. T., Missau, F. C., Pizzolatti, M. G., & Kettle, A. J. (2008). Myricitrin as a substrate and inhibitor of myeloperoxidase: Implications for the pharmacological effects of flavonoids. Free Radical Biology & Medicine, 44(1), 109-120. doi: 10.1016/j.freeradbiomed.2007.09.017
Senthilmohan, S. T., Kettle, A. J., McEwan, M. J., Dummer, J., Edwards, S. J., Wilson, P. F., & Epton, M. J. (2008). Detection of monobromamine, monochloramine and dichloramine using selected ion flow tube mass spectrometry and their relevance as breath markers. Rapid Communications in Mass Spectrometry, 22(5), 677-681. doi: 10.1002/rcm.3418
Harwood, D. T., Nimmo, S. L., Kettle, A. J., Winterbourn, C. C., & Ashby, M. T. (2008). Molecular structure and dynamic properties of a sulfonamide derivative of glutathione that is produced under conditions of oxidative stress by hypochlorous acid. Chemical Research in Toxicology, 21(5), 1011-1016.
Kettle, A. J., Anderson, R. F., Hampton, M. B., & Winterbourn, C. C. (2007). Reactions of superoxide with myeloperoxidase. Biochemistry, 46, 4888-4897.
Åkerström, B., Maghzal, G. J., Winterbourn, C. C., & Kettle, A. J. (2007). The lipocalin α1-microglobulin has radical scavenging activity. Journal of Biological Chemistry, 282(43), 31493-31503.
Senthilmohan, R., & Kettle, A. J. (2006). Bromination and chlorination reactions of myeloperoxidase at physiological concentrations of bromide and chloride. Archives of Biochemistry & Biophysics, 445, 235-244.
Winterbourn, C. C., Hampton, M. B., Livesey, J. H., & Kettle, A. J. (2006). Modeling the reactions of superoxide and myeloperoxidase in the neutrophil phagosome: Implications for microbial killing. Journal of Biological Chemistry, 281(52), 39860-39869.
van Dalen, C. J., Winterbourn, C. C., & Kettle, A. J. (2006). Mechanism of nitrite oxidation by eosinophil peroxidase: Implications for oxidant production and nitration by eosinophils. Biochemical Journal, 394, 707-713.
