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Permanent link (DOI): https://doi.org/10.7939/R3M35C

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4-aminobenzoic acid hydrazide mediated inhibition of Microperoxidase-11: catalytic inhibition by reactive metabolites. Open Access

Descriptions

Other title
Subject/Keyword
DMPO
ESR
Microperoxidase-11
4-aminobenzoic acid hydrazide
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Arvadia, Pratik
Supervisor and department
Siraki, Arno (Pharmaceutical Sciences)
Examining committee member and department
Seubert, John (Pharmaceutical Sciences)
Acker, Jason (Laboratory Medicine and Pathology)
Department
Faculty of Pharmacy and Pharmaceutical Sciences
Specialization

Date accepted
2011-09-28T02:49:16Z
Graduation date
2011-11
Degree
Master of Science
Degree level
Master's
Abstract
Currently, there is lack of clinical therapeutics for inhibiting myeloperoxidase mediated pathogenesis. We used 4-aminobenzoic acid hydrazide (4-ABAH), the most potent irreversible inhibitor of myeloperoxidase and microperoxidase-11 to obtain mechanistic insight on the role of reactive metabolites in catalytic inhibition. We investigated heme spectrum and peroxidase activity of MP-11 in the presence of 4-ABAH. Significant inhibition of MP-11 by 4-ABAH was observed. We performed ESR spin trapping studies on 4-ABAH reactive metabolites using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and detected carbon-centered radicals. We performed MALDI and determined the change in elemental composition that occurred in these reactions. These masses were assigned to free radical metabolites of 4-ABAH and were not observed in reactions containing DMPO. We successfully determined MP-11 immunoreactivity using western blotting. We conclude that the 4-ABAH free radical metabolites bound to MP-11 were involved in the catalytic inhibition.
Language
English
DOI
doi:10.7939/R3M35C
Rights
License granted by pratik arvadia (arvadia@ualberta.ca) on 2011-09-26T18:36:23Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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