Dyachenko Igor A, Murashev Arkadii N, Andreeva Tatyana V, Tsetlin Victor I, Utkin Yuri N
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow region, Russia.
J Venom Res. 2013;4:1-4. Epub 2013 Mar 15.
Phospholipases A2 are represented in snake venoms by several types and possess diverse biological activities including neurotoxicity. Previously, we isolated and characterized two neurotoxic phospholipases A2 (HDP-1 and HDP-2) from the venom of Nikolski's viper (Vipera nikolskii), which were heterodimers composed of two non-covalently bound subunits. Each heterodimer consisted of an enzymatically active basic subunit and an inactive acidic subunit. In this work, we studied the in vivo biological activity of HDP-2 in mice. The acute toxicity (LD50 = 0.38 μg/gm) and maximal tolerated dose (0.1 μg/gm) were determined. In the hot plate test, HDP-2 at the maximal tolerated dose, reliably prolonged the time of the mouse staying on the plate. However, taking into account the neurotoxicity of HDP-2, we believe that this effect may be explained by a general intoxication rather than specific decrease of pain sensitivity. In this respect HDP-2 differs from other heterodimeric phospholipases A2 like crotoxin, which possess analgesic activity. This difference can be explained by the dissimilarity in the structure of the acidic subunits, suggesting an important role of this subunit in analgesic activity.
磷脂酶A2在蛇毒中有多种类型，具有多种生物活性，包括神经毒性。此前，我们从尼氏蝰蛇（Vipera nikolskii）的毒液中分离并鉴定了两种神经毒性磷脂酶A2（HDP - 1和HDP - 2），它们是由两个非共价结合的亚基组成的异二聚体。每个异二聚体由一个具有酶活性的碱性亚基和一个无活性的酸性亚基组成。在这项研究中，我们研究了HDP - 2在小鼠体内的生物活性。测定了其急性毒性（LD50 = 0.38 μg/gm）和最大耐受剂量（0.1 μg/gm）。在热板试验中，最大耐受剂量的HDP - 2能可靠地延长小鼠在热板上停留的时间。然而，考虑到HDP - 2的神经毒性，我们认为这种作用可能是由全身中毒引起的，而不是疼痛敏感性的特异性降低。在这方面，HDP - 2与其他异二聚体磷脂酶A2如响尾蛇毒素不同，后者具有镇痛活性。这种差异可以通过酸性亚基结构的不同来解释，这表明该亚基在镇痛活性中起重要作用。
