title: Plasmodium berghei proteome changes in response to SSJ-183 treatment.
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.
authors.affiliation: Drug Discovery Science Research Center, Hoshi University, Shinagawa, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Chika
authors.initials: C
authors.lastname: Arai
authors.forename: Abu Bakar
authors.initials: AB
authors.lastname: Md
authors.forename: Masataka
authors.initials: M
authors.lastname: Ihara
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D006360:Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects* / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D000962:Antimalarials; D006360:Heat-Shock Proteins; D010078:Oxazines; D020543:Proteome; D011725:Pyridines; C561763:SSJ 183; D019704:Protein Disulfide-Isomerases