Evolution of primary hemostasis in early vertebrates.
Evolution of primary hemostasis in early vertebrates.
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DOI：
10.1371/journal.pone.0008403
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发表时间：
2009-12-23
期刊：
影响因子：
3.7
通讯作者：
Jagadeeswaran P
中科院分区：
文献类型：
--
作者：
Kim S;Carrillo M;Kulkarni V;Jagadeeswaran P
止血是一种防御机制，可在受伤时保护机体止血。最近，我们确定所有已知的主要哺乳动物止血因子在早期脊椎动物中都是保守的。然而，由于它们的血管丰富的鳃会承受高血压并暴露在环境中，因此即使非常小的伤害也可能对鱼类致命。由于胰蛋白酶是凝固蛋白酶的前身，并且由许多胰外细胞（例如内皮细胞和上皮细胞）表达，因此我们假设来自鳃上皮细胞的胰蛋白酶或胰蛋白酶样蛋白酶可以保护这些动物免受受伤后的鳃出血。在本文中，我们确定了在压力或损伤下鱼鳃会释放三种不同的胰蛋白酶到水中，其丝氨酸蛋白酶活性是牛胰蛋白酶的十倍。我们发现这些胰蛋白酶激活血小板并保护鱼免于鳃出血。我们通过分析斑马鱼基因组发现了 27 种蛋白酶激活受体 (PAR)，并根据束缚肽将它们分为五组，根据同源性将它们分为两个家族：PAR1 和 PAR2。我们还发现了 PAR2 家族的一个典型成员 PAR2-21A，它更容易被胰蛋白酶激活，并且 PAR2-21A 束缚肽就像胰蛋白酶一样可以阻止鳃出血。这一发现提供了胰蛋白酶切割血小板表面上的 PAR2 成员的证据。总之，我们相信鳃在进化上被选择产生胰蛋白酶来激活血小板表面的 PAR2 并保护鳃免于出血。我们还推测，胰蛋白酶还可以保护鱼免受由于与血小板快速接触而导致的其他身体损伤造成的出血。因此，这一发现为胰蛋白酶在早期脊椎动物初级止血中的作用提供了证据。
Hemostasis is a defense mechanism which protects the organism in the event of injury to stop bleeding. Recently, we established that all the known major mammalian hemostatic factors are conserved in early vertebrates. However, since their highly vascularized gills experience high blood pressure and are exposed to the environment, even very small injuries could be fatal to fish. Since trypsins are forerunners for coagulation proteases and are expressed by many extrapancreatic cells such as endothelial cells and epithelial cells, we hypothesized that trypsin or trypsin-like proteases from gill epithelial cells may protect these animals from gill bleeding following injuries. In this paper we identified the release of three different trypsins from fish gills into water under stress or injury, which have tenfold greater serine protease activity compared to bovine trypsin. We found that these trypsins activate the thrombocytes and protect the fish from gill bleeding. We found 27 protease-activated receptors (PARs) by analyzing zebrafish genome and classified them into five groups, based on tethering peptides, and two families, PAR1 and PAR2, based on homologies. We also found a canonical member of PAR2 family, PAR2-21A which is activated more readily by trypsin, and PAR2-21A tethering peptide stops gill bleeding just as trypsin. This finding provides evidence that trypsin cleaves a PAR2 member on thrombocyte surface. In conclusion, we believe that the gills are evolutionarily selected to produce trypsin to activate PAR2 on thrombocyte surface and protect the gills from bleeding. We also speculate that trypsin may also protect the fish from bleeding from other body injuries due to quick contact with the thrombocytes. Thus, this finding provides evidence for the role of trypsins in primary hemostasis in early vertebrates.
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