Premium
A quinol peroxidase inhibitor prevents secretion of a leukotoxin from Aggregatibacter actinomycetemcomitans
Author(s) -
Takashima E.,
Yamada H.,
Yajima A.,
Shiomi K.,
Ōmura S.,
Kiyoshi K.
Publication year - 2010
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2009.01211.x
Subject(s) - aggregatibacter actinomycetemcomitans , secretion , peroxidase , periodontitis , microbiology and biotechnology , virulence , chemistry , biology , biochemistry , enzyme , medicine , porphyromonas gingivalis , gene
Takashima E, Yamada H, Yajima A, Shiomi K, Ōmura S, Kiyoshi K. A quinol peroxidase inhibitor prevents secretion of a leukotoxin from Aggregatibacter actinomycetemcomitans. J Periodont Res 2009; doi: 10.1111/j.1600‐0765.2009.01211.x. © 2009 John Wiley & Sons A/S Background and Objective: Quinol peroxidase (QPO) catalyzes peroxidase activity using quinol in the respiratory chain as a substrate . Quinol peroxidase is essential for the secretion of leukotoxin (LtxA), which destroys leukocytes and erythrocytes in humans and is one of the major virulence factors of Aggregatibacter actinomycetemcomitans , which is associated with localized aggressive periodontitis. In the present study, we aimed to find a highly potent QPO inhibitor to attenuate the virulence of A. actinomycetemcomitans. Material and Methods: For screening of QPO inhibitors, QPO activity was measured kinetically by SpectraMax Plus with 96‐well UV plates. Three hundred compounds in the Kitasato Institute for Life Sciences Chemical Library were screened. Secretion of LtxA in the culture supernatant was examined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Cytotoxicity against human promyelocytic leukemia cell line (HL‐60) cells from the culture supernatant was measured by Trypan Blue exclusion test. Results: The present study characterized ascofuranone as a highly potent inhibitor of QPO ( K i = 9.557 ± 0.865 n m ). Ascofuranone inhibited secretion of LtxA by A. actinomycetemcomitans in a dose‐dependent manner, making A. actinomycetemcomitans less pathogenic to HL‐60 cells. Conclusion: Quinol peroxidase inhibitors are promising candidates as alternative drugs for the treatment and prevention of the onset of localized aggressive periodontitis. Using ascofuranone as a seed compound, further study of QPO inhibitors could provide novel chemotherapeutic strategies for controlling localized aggressive periodontitis.