L-amino acid oxidase activity present in fractions of Bothrops jararaca venom is responsible for the induction of programmed cell death in Trypanosoma cruzi.
Bothrops jararaca venom induces programmed cell death in epimastigotes of Trypanosoma cruzi. Here we fractionated the venom and observed that the anti-T. cruzi activity was associated with fractions that present L-amino acid oxidase (L-AAO) activity. L-AAO produces H(2)O(2), which is highly toxic. The addition of catalase to the medium, a H(2)O(2) scavenger, reverted the killing capacity of venom fractions. The anti-T. cruzi activity was also abolished when parasites were cultured in a medium without hydrophobic amino acids that are essential for L-AAO activity. These results were confirmed with a commercial purified L-AAO. Treatment for 24 h with fractions that present L-AAO activity induced parasites cytoplasmic retraction, mitochondrial swelling and DNA fragmentation, all morphological characteristics of programmed cell death. Similar changes were also observed when parasites were treated with H(2)O(2). These results indicate that H(2)O(2), the product of L-AAO reaction, induces programmed cell death explaining the anti-T. cruzi activity of B. jararaca venom.
Deolindo
Poliana
P
Laboratório de Química e Função de Proteínas e Peptídeos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense, Av. Alberto Lamego, 2000, 28013-600 Campos dos Goytacazes, RJ, Brazil.
Teixeira-Ferreira
André S
AS
DaMatta
Renato A
RA
Alves
Elias W
EW
D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D017837:Bothrops / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D005591:Chemical Fractionation; D003435:Crotalid Venoms / Q000737:chemistry / Q000201:enzymology*; D003593:Cytoplasm / Q000187:drug effects; D053938:DNA Fragmentation; D016054:DNA, Protozoan / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050830:L-Amino Acid Oxidase / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D008933:Mitochondrial Swelling / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000981:Antiprotozoal Agents; D003435:Crotalid Venoms; D016054:DNA, Protozoan; D006861:Hydrogen Peroxide; D002374:Catalase; D050830:L-Amino Acid Oxidase