کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2065310 | 1544179 | 2010 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A new type of thrombin inhibitor, noncytotoxic phospholipase A2, from the Naja haje cobra venom A new type of thrombin inhibitor, noncytotoxic phospholipase A2, from the Naja haje cobra venom](/preview/png/2065310.png)
Thrombin is a key enzyme in the blood coagulation cascade and is also involved in carcinogenesis; therefore, its inhibitors are of fundamental and clinical importance. Snake venoms are widely used as sources of proteins that affect blood coagulation. We have isolated a new protein, called TI-Nh, from the Naja haje cobra venom. TI-Nh is a mixed-type inhibitor of thrombin (Ki of 72.8 nM for a synthetic peptide substrate) and effectively inhibits thrombin-induced platelet aggregation with an IC50 value of 0.2 nM. At concentrations up to approximately 50 nM, at which the thrombin-clotting time is substantially prolonged, TI-Nh exerts no detectable effects on both the intrinsic and extrinsic pathways of the coagulation cascade. It does not hydrolyze either fibrinogen or thrombin. Although TI-Nh bears structural features typical of group IB phospholipases A2 (PLA2s), it possesses relatively weak enzymatic activity and is nontoxic to PC12 cells at concentrations up to 15 μM. Nevertheless, TI-Nh evokes neurite outgrowth in these cells at a concentration of approximately 1 μM, similar to cytotoxic snake PLA2s with strong enzymatic activity. TI-Nh is the first thrombin inhibitor found in the venom of the Elapidae snake family, and it is the first phospholipase shown to inhibit thrombin.
Journal: Toxicon - Volume 55, Issues 2–3, February–March 2010, Pages 186–194