Inhibitory effect of fucoidan on the activities of crotaline snake venom myotoxic phospholipases A2
Inhibitory effect of fucoidan on the activities of crotaline snake venom myotoxic phospholipases A2
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DOI：
10.1016/s0006-2952(03)00579-3
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发表时间：
2003-11-15
影响因子：
5.8
通讯作者：
Lomonte, B
中科院分区：
文献类型：
--
作者：
Angulo, Y;Lomonte, B
肌肉毒性磷脂酶 A(2) 是由响尾蛇毒害造成的大部分肌肉坏死的原因。在本研究中，我们研究了岩藻依聚糖（一种从棕色海藻 Fucus vesiculosus 中提取的天然硫酸多糖）对来自巴豆蛇毒液的一组磷脂酶 A(2) 肌肉毒素（Bothrops asper 肌肉毒素 1、11、111 和 IV、Cerrophidion godmani 肌肉毒素 I）的细胞毒性和肌肉毒性活性的保护作用。 和11，Atropoides nummifer 肌肉毒素I 和11，以及Bothriechis schlegelii 肌肉毒素I。所有测试的毒素都被岩藻依聚糖有效抑制其细胞毒性和肌肉毒性作用。这种抑制的基础似乎是岩藻依聚糖和肌肉毒素之间复合物的快速形成，如比浊分析所证明的。使用代表其中三种毒素的膜损伤区域（残基 115-129）的短合成肽研究了岩藻依聚糖在肌肉毒素上的可能结合位点。岩藻依聚糖明显抑制肽的溶细胞活性，表明其能够与这些磷脂酶 A(2) 的 C 末端肌肉毒性区域相互作用。在用 B. asper 的粗毒液实验性蛰入小鼠后，立即局部给药，褐藻糖胶可显着抑制小鼠的肌肉损伤。这些结果鼓励对硫酸岩藻聚糖作为潜在用途的化合物进行进一步研究，以改善对响尾蛇蛇毒的治疗。 (C) 2003 Elsevier Inc. 保留所有权利。
Myotoxic phospholipases A(2) account for most of the muscle necrosis that results from envenenomation by crotaline snakes. In this study, we investigated the protective effect of fucoidan, a natural sulfated polysaccharide obtained from the brown seaweed Fucus vesiculosus, against the cytotoxic and myotoxic activities of a group of phospholipase A(2) myotoxins from crotaline snake venoms: Bothrops asper myotoxins 1, 11, 111, and IV, Cerrophidion godmani myotoxins I and 11, Atropoides nummifer myotoxins I and 11, and Bothriechis schlegelii myotoxin I. All of the toxins tested were efficiently inhibited by fucoidan, in both their cytotoxic and myotoxic effects. The basis for this inhibition appears to be the rapid formation of complexes between fucoidan and myotoxins, as evidenced by turbidimetric analysis. The possible binding site of fucoidan on the myotoxins was investigated using short synthetic peptides that represent the membrane-damaging region (residues 115-129) for three of these toxins. Fucoidan clearly inhibited the cytolytic activity of the peptides, indicating its ability to interact with the C-terminal myotoxic region of these phospholipases A(2). Fucoidan significantly inhibited muscle damage in mice, when administered locally, immediately after experimental envenomation with crude venom from B. asper. These results encourage further studies of sulfated fucans as compounds of potential use to improve the treatment of envenomations by crotaline snakes. (C) 2003 Elsevier Inc. All rights reserved.