Purification, characterization and potent lung lesion activity of an L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom.
L-amino acid oxidases (LAOs) are one of the major components of snake venoms, which possess numerous biological functions. However, little is known of the influence of LAOs on organ lesions. In the present study, a unique LAO from Agkistrodon blomhoffii ussurensis snake venom named ABU-LAO was purified by Heparin-Sepharose FF chromatography followed by an ion-exchange chromatography procedure. The purified ABU-LAO appears a dimer with a molecular mass of approximately 108.8kDa. Kinetics studies showed that ABU-LAO is very active towards its substrates L-Asn, L-Phe, L-Tyr, L-Leu, L-Ile and L-Trp. The most striking observation in the present study is that ABU-LAO causes severe pneumorrhagia, pulmonary interstitial edema, fusion of pulmonary alveoli, cardiac interstitial edema and bleeding when being intravenously injected into BALB/c mice. ABU-LAO also induces liver cell necrosis and release of cytokines including IL-6, IL-12 and IL-2 from highly purified human peripheral blood monocytes and T cells, respectively. In conclusion, ABU-LAO potently induces lesions in lungs and livers. The ability of ABU-LAO will contribute to the understanding of the pathogenesis of snakebite wound.
Wei
Xiao-Long
XL
Allergy and Inflammation Research Institute, The Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xin-ling Road, Shantou, Guangdong 515041, China.
Wei
Ji-Fu
JF
Li
Tao
T
Qiao
Li-Ya
LY
Liu
Yue-Lin
YL
Huang
Tian
T
He
Shao-Heng
SH
D017836:Agkistrodon; D000818:Animals; D003435:Crotalid Venoms / Q000201:enzymology*; D016207:Cytokines / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D050830:L-Amino Acid Oxidase / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D003435:Crotalid Venoms; D016207:Cytokines; D007770:L-Lactate Dehydrogenase; D050830:L-Amino Acid Oxidase