Antitumoural effect of an L-amino acid oxidase isolated from Bothrops jararaca snake venom.
An L-amino acid oxidase (BjarLAAO-I) from Bothrops jararaca snake venom was highly purified using a stepwise sequential chromatography on Sephadex G-75, Benzamidine Sepharose and Phenyl Sepharose. Purified BjarLAAO-I showed a molecular weight around 60,000 under reducing conditions and about 125,000 in the native form, when analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration, respectively. BjarLAAO-I is a homodimeric acidic glycoprotein, pI approximately 5.0, and N-terminal sequence showing close structural homology with other snake venom LAAOs. The purified enzyme catalysed the oxidative deamination of L-amino acids, the most specific substrate being L-Phe. Five amino acids, L-Ser, L-Pro, L-Gly, L-Thr and L-Cys were not oxidized, clearly indicating a significant specificity. BjarLAAO-I significantly inhibited Ehrlich ascites tumour growth and induced an influx of polymorphonuclear cells, as well as spontaneous liberation of H(2)O(2) from peritoneal macrophages. Later, BjarLAAO-I induced mononuclear influx and peritoneal macrophage spreading. Animals treated with BjarLAAO-I showed higher survival time.
de Vieira Santos
Mariana M
MM
Department of Pathology, School of Medicine, São Paulo State University - UNESP, Botucatu, Brazil.
Sant'Ana
Carolina D
CD
Giglio
José R
JR
da Silva
Reinaldo J
RJ
Sampaio
Suely V
SV
Soares
Andreimar M
AM
Fecchio
Denise
D
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017837:Bothrops; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003435:Crotalid Venoms / Q000737:chemistry / Q000201:enzymology*; D004354:Drug Screening Assays, Antitumor; D006861:Hydrogen Peroxide / Q000378:metabolism; D050830:L-Amino Acid Oxidase / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010084:Oxidation-Reduction; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D013045:Species Specificity
D000596:Amino Acids; D000970:Antineoplastic Agents; D003435:Crotalid Venoms; D006861:Hydrogen Peroxide; D050830:L-Amino Acid Oxidase