Trypanosoma cruzi: altered parasites after in vitro treatment with gangliosides, a therapeutic agent in experimental Chagas' disease.
Biochemical and structural modifications were investigated in axenic cultured Trypanosoma cruzi after treatment with gangliosides. Fluorescence anisotropy showed dose dependent increments in parasite membranes of ganglioside treated epimastigotes. NADP-GDH activity increased in parasites treated at day 4 (13%), 7 (137.2%), and 14 (28.50%) while NAD-MDH but decreased from day 7 to 21 (-5.74%, -32.22%, -27.92%). Treated parasites presented electron-lucent vacuoles opposite to the cytostoma, multilamellar bodies and dilated mitochondrion cristae, disorganized kinetoplast and altered heterochromatin structure. Gangliosides inhibited fusogenic ability (80%) and PLA2 activity (>75%) from the parasite. The same occurred with anti-PLA2 antibodies. Trypomastigotes suffered loss of cytoplasmic material and organelles when GM1 was present in culture medium. We propose that exogenous gangliosides produced: altered lipid order, inhibited membrane enzymes, the parasite energy source shifted from glucose to amino acids, ending on a structural transformation which signals parasite cell death.
Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas de la Universidad Nacional de Córdoba, Pabellón Argentina, no. 2 piso, Ciudad Universitaria, CP:5000, Córdoba CD, Córdoba, Argentina. scossy04101962@yahoo.com.ar
S
S
Cossy Isasi
M
M
Rodríguez
B M I
BM
Pereira
C
C
Díaz-Luján
R E
RE
Fretes
D I
DI
Haüen
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002522:Chlorocebus aethiops; D005732:Gangliosides / Q000494:pharmacology*; D018086:Glutamate Dehydrogenase (NADP+) / Q000032:analysis; D008291:Malate Dehydrogenase / Q000032:analysis; D046529:Microscopy, Electron, Transmission; D015800:Protozoan Proteins / Q000032:analysis / Q000737:chemistry; D011874:Radiometry; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D014709:Vero Cells; D014783:Viscosity / Q000187:drug effects
D005732:Gangliosides; D015800:Protozoan Proteins; D008291:Malate Dehydrogenase; D018086:Glutamate Dehydrogenase (NADP+)