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首页> 外文期刊>Biochemical Pharmacology >Isolation and pharmacological characterization of alpha-Elapitoxin-Na1a, a novel short-chain postsynaptic neurotoxin from the venom of the Chinese Cobra (Naja atra)
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Isolation and pharmacological characterization of alpha-Elapitoxin-Na1a, a novel short-chain postsynaptic neurotoxin from the venom of the Chinese Cobra (Naja atra)

机译：α-elapitoxin-Na1a的分离和药理表征，一种来自中国Cobra毒液的新型短链突触神经毒素（Naja Atra）

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The Chinese Cobra (Naja atra) is an elapid snake of major medical importance in southern China. Although previous studies have shown that postsynaptic neurotoxins account for 11-23% of N. atra venom, envenomed patients do not display marked signs of neurotoxicity. We have previously shown that the lack of clinical neurotoxicity following snake envenoming by some species with `neurotoxic' venoms may be related to the high prevalence of short-chain postsynaptic neurotoxins in these venoms. In this study, we describe the isolation and characterization of alpha-Elapitoxin-Na1a (alpha-EPTX-Na1a; 6949 Da), a short-chain postsynaptic neurotoxin, which accounts for approximately 9% of N. atra crude venom. alpha-EPTX-Na1a (30-300 nM) produced concentration-dependent inhibition of indirect-twitches, with a t90 value of 17 +/- 2 min at 300 nM, and abolished contractile responses to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The prior addition of either Chinese N. atra monovalent antivenom (0.3 U/ml) or Australian polyvalent snake antivenom (2.4 U/ml), prevented the in vitro neurotoxic effects of alpha-EPTX-Na1a (30 nM). Addition of each of these antivenoms at the t(90) time point partially reversed the in vitro neurotoxicity caused by alpha-EPTX-Na1a (30 nM). The inhibition of indirect twitches by alpha-EPTX-Na1a (30 nM) was not reversed by repeatedly washing the tissue. alpha-EPTX-Na1a displayed pseudo-irreversible antagonism of concentration-response curves to carbachol with a pA(2) value of 8.21. De novo protein sequencing of alpha-EPTX-Na1a revealed a typical short-chain postsynaptic neurotoxin profile of 62 amino acids which shared > 98% amino acid sequence similarity with short-chain postsynaptic neurotoxins from other Naja species. When compared to short-chain neurotoxins isolated from cobras in China, alpha-EPTX-Na1a contained novel residues K47Q (i.e. lysine to glutamine), N48T (i.e. asparagine to threonine) and G49A (i.e. glycine to alanine). In conclusion, alpha-EPTX-Na1a is a potent, pseudo-irreversible, short-chain neurotoxin. The high prevalence of alpha-EPTX-Na1a in Chinese N. atra venom is likely to explain the mild neurotoxicity experienced by envenomed patients.
机译：中国Cobra（Naja Atra）是中国南方重大医疗重点的矩阵。虽然之前的研究表明，突触后神经毒素占11-23％的N. ATRA毒液，envenomed患者不显示出明显的神经毒性迹象。我们之前已经表明，通过某种物种与“神经毒性”毒液刺激的蛇缺乏临床神经毒性可能与这些毒液中短链突触神经毒素的高患病率有关。在这项研究中，我们描述了α-Elapitoxin-Na1a（α-EPTX-Na1a; 6949Da）的分离和表征，短链突触后神经毒素，其占N.TARRA粗毒液的约9％。 α-EPTX-NA1A（30-300nm）产生浓度依赖性痉挛的抑制作用，T90值为300nm，在小鸡Biventer中废除了对外源乙酰胆碱和卡巴山的收缩反应颈神经肌肉制备。先前添加中医N. ATRA单价抗静电（0.3u / ml）或澳大利亚多元蛇蛇毒抗动物（2.4U / ml），防止了α-EPTX-Na1a（30nm）的体外神经毒性作用。在T（90）时点在T（90）时间点中的每一个的添加中的每一个部分地反转由α-EPTX-Na1a（30nm）引起的体外神经毒性。通过反复洗涤组织，通过α-EPTX-NA1A（30nm）对间接抽搐的抑制性不反转。 Alpha-EPTX-NA1A显示浓度 - 响应曲线的伪不可逆对抗，PA（2）值为8.21。 α-EPTX-Na1a的De Novo蛋白序列显示了62个氨基酸的典型短链后神经毒素曲线，其与来自其他Naja物种的短链突触神经毒素共享> 98％氨基酸序列相似性。与从中国中胶囊分离的短链神经毒素相比，α-EPTX-NA1A含有新的残基K47Q（即赖氨酸至谷氨酰胺），N48T（即氨氨基至苏氨酸）和G49a（即甘氨酸至丙氨酸）。总之，α-EPTX-Na1a是一种有效的，伪不可逆转的短链神经毒素。 α-EPTX-NA1A在中国人N. ATRA毒液中的高患病率可能解释envenomed患者体验的轻度神经毒性。

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