1. Plasmodium berghei proteome changes in response to SSJ-183 treatment.
- Author
-
Lu J, Arai C, Md AB, and Ihara M
- Subjects
- Animals, Antimalarials pharmacology, Heat-Shock Proteins metabolism, Mice, Oxazines chemistry, Plasmodium berghei metabolism, Protein Disulfide-Isomerases metabolism, Pyridines chemistry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Antimalarials chemistry, Electrophoresis, Gel, Two-Dimensional methods, Oxazines pharmacology, Plasmodium berghei drug effects, Proteome analysis, Pyridines pharmacology
- Abstract
The benzo[a]phenoxazine derivative, SSJ-183 has shown excellent anti-malarial efficacy and safety. However, its mechanism of action is unclear. We investigated the effect of SSJ-183 on the rodent malarial parasite, Plasmodium berghei. We analyzed changes in protein expression in the erythrocytic cycle of P. berghei with or without 18 h of SSJ-183 treatment by two-dimensional gel electrophoresis. We confirmed results with matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight tandem mass spectrometry. After treatment, seven main proteins were significantly down-regulated, and two were up-regulated; results were reproduced in three independent tests. Some of these proteins were hypothetical parasite proteins or unnamed host products. However, three proteins were identified as a heat shock protein, a disulfide isomerase precursor, and berghepain-2 from P. berghei. All three showed reduced expression after SSJ-183 treatment. This suggested that SSJ-183 was a good anti-malarial drug candidate because it targeted parasite chaperone proteins., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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