Functional variability of snake venom metalloproteinases: adaptive advantages in targeting different prey and implications for human envenomation.

Functional variability of snake venom metalloproteinases: adaptive advantages in targeting different prey and implications for human envenomation.
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DOI:
10.1371/journal.pone.0109651
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Moura-da-Silva AM
Moura-da-Silva AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bernardoni JL;Sousa LF;Wermelinger LS;Lopes AS;Prezoto BC;Serrano SM;Zingali RB;Moura-da-Silva AM

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蛇毒金属蛋白酶(SVMPs)是大多数毒蛇毒液中的主要成分,可引起毒蛇中毒动物的止血系统和组织紊乱。这些干扰与人类被蛇咬伤的病理有关,似乎对捕获和消化蛇的猎物以及躲避捕食者至关重要。svmp是一种多功能的毒液毒素家族,作用于不同的止血靶点,这些靶点以不同的结构形式存在于毒液中。然而,在某些毒液中表达大量不同svmp的原因尚不清楚。在这项研究中,我们评估了五种分离的SVMPs对人类、鸟类和小型啮齿动物血液凝固的干扰。P-III类SVMPs(分数Ic, IIb和IIc)具有溶明胶和出血活性,其中两种也具有溶纤维蛋白活性。P-I类SVMPs (IVa和IVb部分)仅具有纤溶性。P-III类SVMPs可缩短人血浆的凝血时间。IIc组分为凝血酶原激活剂,Ic组分为X因子激活剂。在缺乏Ca2+的情况下,在含有Ic、IIb和部分含有IIc的鸡血液样品中观察到牢固的凝块。相比之下,在没有Ca2+的情况下,只有部分IIc能够在大鼠血液中诱导凝固。总之,在新魏氏双胞杆菌毒液中发现了不同功能形式的SVMPs,它们影响人类、鸟类和小型啮齿动物凝血系统的不同机制。不同的svmp似乎更专注于老鼠或鸡的血液,这加强了目前的假设,即毒素的多样性提高了蛇捕食不同猎物或躲避不同捕食者的可能性。这种功能的多样性也影响了人类出血的复杂性,因为考虑到人类对毒液反应的复杂性,svmp将针对不同的止血机制。
Snake venom metalloproteinases (SVMPs) are major components in most viperid venoms that induce disturbances in the hemostatic system and tissues of animals envenomated by snakes. These disturbances are involved in human pathology of snake bites and appear to be essential for the capture and digestion of snake's prey and avoidance of predators. SVMPs are a versatile family of venom toxins acting on different hemostatic targets which are present in venoms in distinct structural forms. However, the reason why a large number of different SVMPs are expressed in some venoms is still unclear. In this study, we evaluated the interference of five isolated SVMPs in blood coagulation of humans, birds and small rodents. P-III class SVMPs (fractions Ic, IIb and IIc) possess gelatinolytic and hemorrhagic activities, and, of these, two also show fibrinolytic activity. P-I class SVMPs (fractions IVa and IVb) are only fibrinolytic. P-III class SVMPs reduced clotting time of human plasma. Fraction IIc was characterized as prothrombin activator and fraction Ic as factor X activator. In the absence of Ca2+, a firm clot was observed in chicken blood samples with fractions Ic, IIb and partially with fraction IIc. In contrast, without Ca2+, only fraction IIc was able to induce a firm clot in rat blood. In conclusion, functionally distinct forms of SVMPs were found in B. neuwiedi venom that affect distinct mechanisms in the coagulation system of humans, birds and small rodents. Distinct SVMPs appear to be more specialized to rat or chicken blood, strengthening the current hypothesis that toxin diversity enhances the possibilities of the snakes for hunting different prey or evading different predators. This functional diversity also impacts the complexity of human envenoming since different hemostatic mechanisms will be targeted by SVMPs accounting for the complexity of the response of humans to venoms.
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