alexa Schistosoma japonicum GSH S-transferase Sj26 is not the molecular target of praziquantel action.
Veterinary Sciences

Veterinary Sciences

Journal of Veterinary Science & Technology

Author(s): Milhon JL, Thiboldeaux RL, Glowac K, Tracy JW

Abstract Share this page

Abstract It has been suggested that Sj26, a Schistosoma japonicum GSH S-transferase, is the molecular target of the antischistosomal drug praziquantel (McTigue et al., 1995, J. Mol. Biol. 246, 21-27). We tested this hypothesis by asking two questions: (1) does praziquantel inhibit Sj26 activity with a variety of model substrates; and (2) does praziquantel prevent the binding to Sj26 of physiologically relevant nonsubstrate ligands? High concentrations of praziquantel (up to 500 microM) did not inhibit Sj26 activity using the model substrates 1-chloro-2,4-dinitrobenzene, 3,4-dichloronitrobenzene, or ethacrynic acid. Sj26 had no measurable activity with two higher molecular weight GSH S-transferase substrates: 5-androsten-3,17-dione and sulfobromophthalein. We also assessed the ability of praziquantel to prevent the inhibition of Sj26 by a series of S-alkyl-GSH conjugates. The half-maximal inhibitory concentrations of S-hexyl-GSH, S-octyl-GSH, and S-decyl-GSH (10, 10, and 5 microM, respectively) for Sj26 were not affected by up to 500 microM praziquantel. This suggests that praziquantel does not compete with GSH for Sj26 binding. In order to determine if praziquantel disrupts binding of nonsubstrate ligands to Sj26, we tested praziquantel for its ability to prevent the inhibition of Sj26 by both bilirubin and hematin. Praziquantel (100 or 500 microM) did not alter inhibition of Sj26 by 3 microM bilirubin, but partially protected Sj26 against inhibition by hematin (0.1 to 2.0 microM). Interestingly, in a similar reaction, 100 microM S-methyl-GSH protected Sj26 from inhibition equally as well as praziquantel. Bovine serum albumin (5 microM) completely protected against inhibition by 1 microM hematin. These results indicate that although praziquantel partially protects Sj26 from hematin inhibition, this protection is neither specific to praziquantel nor physiologically relevant. Our results do not support the hypothesis that the mechanism of praziquantel action involves competitive inhibition of Sj26 catalytic activity or blocking binding of nonsubstrate ligands. We can, therefore, find no evidence that Sj26 is the molecular target of the antischistosomal activity of praziquantel. This article was published in Exp Parasitol and referenced in Journal of Veterinary Science & Technology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]ine.com

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords