TY - JOUR
T1 - Inhibition of human platelet aggregation by L-amino acid oxidase purified from Naja naja kaouthia venom
AU - Sakurai, Yoshihiko
AU - Takatsuka, Hideo
AU - Yoshioka, Akira
AU - Matsui, Taei
AU - Suzuki, Masami
AU - Titani, Koiti
AU - Fujimura, Yoshihiro
N1 - Funding Information:
We are grateful to Dr Brian Potterf in NIH for manuscript revisions. This work was supported in part by a research grant (8A-1) for Cardiovascular Diseases to Yoshihiro Fujimura from the Japanese Ministry of Health and Welfare, and by Grants-in-Aid to Koiti Titani from the Fujita Health University and the Uehara Memorial Foundation.
PY - 2001
Y1 - 2001
N2 - L-Amino acid oxidase (LAO) widely exists in snake venoms. Purification of LAO from the Naja naja kaouthia (monocellate cobra) venom has been reported (Tan and Swaminathan, 1992), but its structural characterization and physiological function remained to be determined. The function of snake venom LAOs in hemostasis, especially their effect on platelet aggregation, has been controversial. We determined the N-terminal amino acid sequence of the N. n. kaouthia LAO named K-LAO to be DDRRSPLEECFQQNDYEEFLEIAKNGLKKTxNPKHVXxV (38 residues). The protein data base search revealed that the enzyme had high similarities with other snake venom LAOs. Further, platelet aggregation studies revealed that K-LAO functionally did not induce platelet aggregation in a platelet-rich plasma system, but that it inhibited platelet aggregation induced by agonists such as ADP, collagen and ristocetin in a dose-dependent manner. K-LAO diminished platelet aggregation more intensely under low than high shear stress. This inhibitory activity of K-LAO on either ristocetin-induced or shear-induced platelet aggregation was quenched by addition of catalase. These results indicate that K-LAO functions as an inhibitor to platelet aggregation through the formation of hydrogen peroxide. The enzyme may contribute to the development of a severe hematological disorder due to cobra envenomation.
AB - L-Amino acid oxidase (LAO) widely exists in snake venoms. Purification of LAO from the Naja naja kaouthia (monocellate cobra) venom has been reported (Tan and Swaminathan, 1992), but its structural characterization and physiological function remained to be determined. The function of snake venom LAOs in hemostasis, especially their effect on platelet aggregation, has been controversial. We determined the N-terminal amino acid sequence of the N. n. kaouthia LAO named K-LAO to be DDRRSPLEECFQQNDYEEFLEIAKNGLKKTxNPKHVXxV (38 residues). The protein data base search revealed that the enzyme had high similarities with other snake venom LAOs. Further, platelet aggregation studies revealed that K-LAO functionally did not induce platelet aggregation in a platelet-rich plasma system, but that it inhibited platelet aggregation induced by agonists such as ADP, collagen and ristocetin in a dose-dependent manner. K-LAO diminished platelet aggregation more intensely under low than high shear stress. This inhibitory activity of K-LAO on either ristocetin-induced or shear-induced platelet aggregation was quenched by addition of catalase. These results indicate that K-LAO functions as an inhibitor to platelet aggregation through the formation of hydrogen peroxide. The enzyme may contribute to the development of a severe hematological disorder due to cobra envenomation.
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U2 - 10.1016/S0041-0101(01)00133-7
DO - 10.1016/S0041-0101(01)00133-7
M3 - Article
C2 - 11600144
AN - SCOPUS:0034792723
SN - 0041-0101
VL - 39
SP - 1827
EP - 1833
JO - Toxicon
JF - Toxicon
IS - 12
ER -