title: Partial characterization of Plasmodium falciparum trophozoite proteome under treatment with quinine, mefloquine and the natural antiplasmodial diosgenone.
abstract: BACKGROUND
  Despite efforts to control malaria, around 10% of the world population is at risk of acquiring this disease. Plasmodium falciparum accounts for the majority of severe cases and deaths. Malaria control programs have failed due to the therapeutic failure of first-line antimalarials and to parasite resistance. Thus, new and better therapeutic alternatives are required. Proteomic analysis allows determination of protein expression levels under drug pressure, leading to the identification of new therapeutic drug targets and their mechanisms of action.
  
  
  OBJECTIVE
  The aim of this study was to analyze qualitatively the expression of P.falciparum trophozoite proteins (strain ITG2), after exposure to antimalarial drugs, through a proteomic approach.
  
  
  METHODS
  In vitro cultured synchronized parasites were treated with quinine, mefloquine and the natural antiplasmodial diosgenone. Protein extracts were prepared and analyzed by two-dimensional electrophoresis. The differentially expressed proteins were selected and identified by MALDI-TOF mass spectrometry.
  
  
  RESULTS
  The following proteins were identified among those differentially expressed in the parasite in the presence of the drugs tested: enolase (PF10_0155), calcium-binding protein (PF11_0098), chaperonin (PFL0740c), the host cell invasion protein (PF10_0268) and proteins related to redox processes (MAL8P1.17). These findings are consistent with results of previous studies where the parasite was submitted to pressure with other antimalarial drugs.
  
  
  CONCLUSIONS
  The observed changes in the P. falciparum trophozoite protein profile induced by antimalarial drugs involved proteins mainly related to the general stress response.
authors: Grupo Malaria, Facultad de Medicina, Universidad de antioquia.
authors: César
authors: C
authors: Segura
authors: Grupo Malaria, Facultad de Medicina, Universidad de antioquia.
authors: Yesid
authors: Y
authors: Cuesta-Astroz
authors: Laboratorio de Infectología y Parasitología Molecular, Hospital Clementino Fraga Filho, Universidad Federal de Rio de Janeiro.
authors: Camila
authors: C
authors: Nunes-Batista
authors: Laboratorio de Infectología y Parasitología Molecular, Hospital Clementino Fraga Filho, Universidad Federal de Rio de Janeiro.
authors: Mariano
authors: M
authors: Zalis
authors: Unidad Multidisciplinaria de Genómica, Instituto de Biofísica Carlos Chagas Filho, Universidad Federal de Rio de Janeiro.
authors: Wanda Maria de Almeida
authors: WM
authors: von Krüger
authors: Unidad Multidisciplinaria de Genómica, Instituto de Biofísica Carlos Chagas Filho, Universidad Federal de Rio de Janeiro.
authors: Paulo
authors: P
authors: Mascarello Bisch
mesh_terms: D000595:Amino Acid Sequence; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004912:Erythrocytes / Q000469:parasitology; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D015767:Mefloquine / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D020543:Proteome; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D011803:Quinine / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013141:Spiro Compounds / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D006360:Heat-Shock Proteins; D020543:Proteome; D015800:Protozoan Proteins; D013141:Spiro Compounds; D014315:Triterpenes; C469690:diosgenone; D011803:Quinine; D015767:Mefloquine