title: Cell cycle arrest evidence, parasiticidal and bactericidal properties induced by L-amino acid oxidase from Bothrops atrox snake venom.
abstract: The present article describes an l-amino acid oxidase from Bothrops atrox snake venom as with antiprotozoal activities in Trypanosoma cruzi and in different species of Leishmania (Leishmania braziliensis, Leishmania donovani and Leishmania major). Leishmanicidal effects were inhibited by catalase, suggesting that they are mediated by H(2)O(2) production. Leishmania spp. cause a spectrum of diseases, ranging from self-healing ulcers to disseminated and often fatal infections, depending on the species involved and the host's immune response. BatroxLAAO also displays bactericidal activity against both Gram-positive and Gram-negative bacteria. The apoptosis induced by BatroxLAAO on HL-60 cell lines and PBMC cells was determined by morphological cell evaluation using a mix of fluorescent dyes. As revealed by flow cytometry analysis, suppression of cell proliferation with BatroxLAAO was accompanied by the significant accumulation of cells in the G0/G1 phase boundary in HL-60 cells. BatroxLAAO at 25 μg/mL and 50 μg/mL blocked G0-G1 transition, resulting in G0/G1 phase cell cycle arrest, thereby delaying the progression of cells through S and G2/M phase in HL-60 cells. This was shown by an accentuated decrease in the proportion of cells in S phase, and the almost absence of G2/M phase cell population. BatroxLAAO is an interesting enzyme that provides a better understanding of the ophidian envenomation mechanism, and has biotechnological potential as a model for therapeutic agents.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Av do Café s/n, 14040-903 Ribeirao Preto, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: de Melo Alves Paiva
authors.forename: Raquel
authors.initials: R
authors.lastname: de Freitas Figueiredo
authors.forename: Gilmara Ausech
authors.initials: GA
authors.lastname: Antonucci
authors.forename: Helder Henrique
authors.initials: HH
authors.lastname: Paiva
authors.forename: Maria
authors.initials: M
authors.lastname: de Lourdes Pires Bianchi
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Rodrigues
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lucarini
authors.forename: Renato Cesar
authors.initials: RC
authors.lastname: Caetano
authors.forename: Rosemeire Cristina
authors.initials: RC
authors.lastname: Linhari Rodrigues Pietro
authors.forename: Carlos Henrique
authors.initials: CH
authors.lastname: Martins
authors.forename: Sérgio
authors.initials: S
authors.lastname: de Albuquerque
authors.forename: Suely Vilela
authors.initials: SV
authors.lastname: Sampaio
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D017837:Bothrops; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003435:Crotalid Venoms / Q000201:enzymology*; D018922:HL-60 Cells; D006801:Humans; D050830:L-Amino Acid Oxidase / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009336:Necrosis; D021261:Parasitic Sensitivity Tests; D014344:Trypanocidal Agents / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D003435:Crotalid Venoms; D014344:Trypanocidal Agents; D050830:L-Amino Acid Oxidase