A novel fibrinogenase from Agkistrodon acutus venom protects against DIC via direct degradation of thrombosis and activation of protein C
| Autor: | Jie-zhen, Qi, Xi, Lin, Jia-shu, Chen, Zhen-hua, Huang, Bi-tao, Qiu, Peng-xin, Qiu, Guang-mei, Yan |
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| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_treatment Pharmacology Fibrinogen Biochemistry In vivo hemic and lymphatic diseases Fibrinolysis Crotalid Venoms Plasminogen Activator Inhibitor 1 Human Umbilical Vein Endothelial Cells Medicine Animals Humans Platelet Disseminated intravascular coagulation business.industry Antithrombin Serine Endopeptidases Endothelial Cells Thrombosis Disseminated Intravascular Coagulation medicine.disease Urokinase-Type Plasminogen Activator Coagulation Gene Expression Regulation Tissue Plasminogen Activator Immunology Kidney Diseases Rabbits Agkistrodon Chemical and Drug Induced Liver Injury business Protein C circulatory and respiratory physiology medicine.drug |
| Zdroj: | Biochemical pharmacology. 84(7) |
| ISSN: | 1873-2968 |
| Popis: | The incidence of disseminated intravascular coagulation (DIC), which leads to multiple organ dysfunction and high mortality, has remained constant in recent years. At present, treatments of DIC have focused on preventing cytokine induction, inhibiting coagulation processes and promoting fibrinolysis. Recent clinical trials have supported the use of antithrombin and activated protein C supplementation in DIC. To better understand the mechanism of treatment on DIC, we here report a novel fibrinogenase from Agkistrodon acutus (FIIa) that effectively protected against LPS-induced DIC in a rabbit model, and detected the tissue factors expression in HUVE cells after using FIIa. In vivo, administration of FIIa reduced hepatic and renal damage, increased the concentration of fibrinogen, the activities of protein C, the platelet count, APTT, PT, FDP, the level of AT-III and t-PA, decreased the level of PAI-1, and increased survival rate in LPS-induced DIC rabbits. In vitro experiments, we further confirmed that FIIa up-regulated the expression of t-PA and u-PA, down-regulated the expression of PAI-1, and directly activated protein C. Our findings suggest that FIIa could effectively protect against DIC via direct degradation of microthrombi and activation of protein C as well as provide a novel strategy to develop a single proteinase molecule for targeting the main pathological processes of this disease. |
| Databáze: | OpenAIRE |
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