Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, 13083-970 Campinas, SP, Brazil.
Biomed Res Int. 2013;2013:591470. doi: 10.1155/2013/591470. Epub 2012 Dec 30.
BrTX-I, a PLA2, was purified from Bothrops roedingeri venom after only one chromatographic step using reverse-phase HPLC on μ-Bondapak C-18 column. A molecular mass of 14358.69 Da was determined by MALDI-TOF mass spectrometry. Amino acid analysis showed a high content of hydrophobic and basic amino acids as well as 14 half-cysteine residues. The total amino acid sequence was obtained using SwissProt database and showed high amino acid sequence identity with other PLA2 from snake venom. The amino acid composition showed that BrTX-I has a high content of Lys, Tyr, Gly, Pro, and 14 half-Cys residues, typical of a basic PLA2. BrTX-I presented PLA2 activity and showed a minimum sigmoidal behavior, reaching its maximal activity at pH 8.0, 35-45°C, and required Ca(2+). In vitro, the whole venom and BrTX-I caused a neuromuscular blockade in biventer cervicis preparations in a similar way to other Bothrops species. BrTX-I induced myonecrosis and oedema-forming activity analyzed through injection of the purified BrTX-I in mice. Since BrTX-I exerts a strong proinflammatory effect, the enzymatic phospholipid hydrolysis might be relevant for these phenomena; incrementing levels of IL-1, IL-6, and TNF α were observed at 15 min, 30 min, one, two, and six hours postinjection, respectively.
BrTX-I 是一种 PLA2,从罗德里格蛇毒中经过一步反相 HPLC 纯化,使用 μ-Bondapak C-18 柱。MALDI-TOF 质谱法测定其分子量为 14358.69Da。氨基酸分析表明,它含有高比例的疏水性和碱性氨基酸以及 14 个半胱氨酸残基。通过 SwissProt 数据库获得了全长氨基酸序列,与其他蛇毒 PLA2 具有高度的氨基酸序列同一性。氨基酸组成表明,BrTX-I 具有高含量的 Lys、Tyr、Gly、Pro 和 14 个半胱氨酸残基,这是一种碱性 PLA2 的典型特征。BrTX-I 具有 PLA2 活性,并表现出最小的 S 型行为,在 pH8.0、35-45°C 和需要 Ca(2+)的条件下达到最大活性。在体外,全毒液和 BrTX-I 以类似于其他罗德里格蛇种的方式引起双颈椎制剂的神经肌肉阻滞。BrTX-I 诱导肌坏死和水肿形成活性,通过向小鼠注射纯化的 BrTX-I 进行分析。由于 BrTX-I 具有强烈的促炎作用,酶解磷脂水解可能与这些现象有关;在注射后 15 分钟、30 分钟、1 小时、2 小时和 6 小时,分别观察到 IL-1、IL-6 和 TNFα 水平的增加。