L-amino acid oxidase from Naja atra venom activates and binds to human platelets.
An L-amino acid oxidase (LAAO), NA-LAAO, was purified from the venom of Naja atra. Its N-terminal sequence shows great similarity with LAAOs from other snake venoms. NA-LAAO dose-dependently induced aggregation of washed human platelets. However, it had no activity on platelets in platelet-rich plasma. A low concentration of NA-LAAO greatly promoted the effect of hydrogen peroxide, whereas hydrogen peroxide itself had little activation effect on platelets. NA-LAAO induced tyrosine phosphorylation of a number of platelet proteins including Src kinase, spleen tyrosine kinase, and phospholipase Cgamma2. Unlike convulxin, Fc receptor gamma chain and T lymphocyte adapter protein are not phosphorylated in NA-LAAO-activated platelets, suggesting an activation mechanism different from the glycoprotein VI pathway. Catalase inhibited the platelet aggregation and platelet protein phosphorylation induced by NA-LAAO. NA-LAAO bound to fixed platelets as well as to platelet lysates of Western blots. Furthermore, affinity chromatography of platelet proteins on an NA-LAAO-Sepharose 4B column isolated a few platelet membrane proteins, suggesting that binding of NA-LAAO to the platelet membrane might play a role in its action on platelets.
Li
Rui
R
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Zhu
Shaowen
S
Wu
Jianbo
J
Wang
Wanyu
W
Lu
Qiumin
Q
Clemetson
Kenneth J
KJ
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004546:Elapid Venoms / Q000201:enzymology*; D017815:Elapidae; D006801:Humans; D050830:L-Amino Acid Oxidase / Q000008:administration & dosage* / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*
D004546:Elapid Venoms; D050830:L-Amino Acid Oxidase