Tachoua Wafa, Boukhalfa-Abib Hinda, Laraba-Djebari Fatima
USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP 32, El-Alia Bab Ezzouar, 16111, Algiers, Algeria.
J Biochem Mol Toxicol. 2017 Jul;31(7). doi: 10.1002/jbt.21899. Epub 2017 Feb 28.
Snake venom metalloproteinases are the most abundant toxins in Viperidae venoms. In this study, a new hemorrhagin, Cc HSM-III (66 kDa), was purified from Cerastes cerastes venom by gel filtration, ion exchange, and reversed-phase high-performance liquid chromatographies. The analysis of Cc HSM-III by liquid chromatography with a tandem mass spectrometry revealed 32 peptides sharing a homology with P-III metalloproteinases from Echis ocellatus snake venom. Cc HSM-III displays hemorrhagic activity with a minimal hemorrhagic dose of 5 μg, which is abolished by ethylene diamine tetracetic acid but not by phenylmethylsulfonyl fluoride. The mechanism underlying Cc HSM-III hemorrhagic activity is probably due to its extensive proteolytic activity against type IV collagen. Cc HSM-III induces local tissue damage and an inflammatory response by upregulating both matrix metalloproteinase 2 and 9 in skin of mice. Thus, Cc HSM-III may play a key role in the pathogenesis of C. cerastes envenomation.
蛇毒金属蛋白酶是蝰蛇科蛇毒中含量最丰富的毒素。在本研究中，通过凝胶过滤、离子交换和反相高效液相色谱法从角蝰蛇毒中纯化出一种新的出血毒素Cc HSM-III（66 kDa）。利用液相色谱-串联质谱法对Cc HSM-III进行分析，结果显示有32个肽段与锯鳞蝰蛇毒中的P-III金属蛋白酶具有同源性。Cc HSM-III具有出血活性，最小出血剂量为5μg，该活性可被乙二胺四乙酸消除，但不能被苯甲基磺酰氟消除。Cc HSM-III出血活性的潜在机制可能是其对IV型胶原具有广泛的蛋白水解活性。Cc HSM-III通过上调小鼠皮肤中基质金属蛋白酶2和9的表达，诱导局部组织损伤和炎症反应。因此，Cc HSM-III可能在角蝰蛇咬伤的发病机制中起关键作用。
