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Free Radical Research
Group - Our People
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Dr Tony Kettle PhD
Research Professor
PhD (Biochemistry) Otago University 1989
MSc (Biochemistry) Simon Fraser University 1985
BSc Hons (Chemistry) Otago University 1979
tony.kettle@otago.ac.nz
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All of my work is centred on a green enzyme called myeloperoxidase.
This complicated but fascinating enzyme uses hydrogen peroxide
to oxidize chloride to hypochlorous acid or chlorine bleach.
It also oxidizes many other biological compounds to reactive
free radicals. Likely physiological substrates include chloride,
thiocyanate, nitric oxide, nitrite, ascorbate, urate, and tyrosine.
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Myeloperoxidase is the most abundant protein in neutrophils.
These white blood cells are our primary defenders against invading
bacteria. When stimulated, neutrophils produce massive amounts
of the free radical superoxide. The superoxide is converted to
hydrogen peroxide and ultimately hypochlorous acid, which reacts
with and kills bacteria. Neutrophils also cause tissue damage
in many inflammatory pathologies such as rheumatoid arthritis,
cystic fibrosis, inflammatory bowel disease, sepsis, and neonatal
lung disease. A particular interest of mine is how to block the
activity of myeloperoxidase so that it can be prevented from
promoting inflammatory tissue damage.
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Our group has been intrigued as to why neutrophils produce
superoxide. We have proposed that this relatively benign free
radical optmizes production of hypochlorous acid by neutrophils.
We are still very much interested in how superoxide impacts on
the enzymology of myeloperoxidase. We have shown that superoxide
is required as a cofactor for the catalase activity of myeloperoxidase.
It also reacts with phenolic radicals produced by myeloperoxidase
to form organic peroxides. These peroxides may exacerbate oxidative
damage in inflammation.
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We are investigating how reactive oxidants contribute to disease
processes by measuring biomarkers of protein oxidation. The
biomarkers include chlorotyrosine, bromotyrosine, nitrotyrosine,
ortho-tyrosine, and protein carbonyls. Using these biomarkers
we have shown that hypochlorous acid and hypobromous acid are
produced in the lungs of premature infants, asthmatics, and
infants with cystic fibrosis.
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We use chlorine bleach inside &
outside our bodies to kill germs.
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Current projects include:
- Involvement of myeloperoxidase in the lung damage suffered by children
with cystic fibrosis:
- The contribution eosinophil peroxidase makes to deteriorating lung
function in asthmatics.
- The enzymology of myeloperoxidase.
- Bacterial killing mechanisms of neutrophils.
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