马兆瑞;王振;马亚瑞;何宇;杨章民;

• 1:陕西师范大学生命科学学院
• 2:集美大学诚毅学院
• 3:渭南职业技术学院

摘要(Abstract)：

蛇毒突触前磷脂酶A2神经毒素(Snake presynaptic phospholipase A2 neurotoxins,SPANs)是蛇毒中毒性最大的成分之一,主要作用于脊椎动物神经-肌肉接头(Neuromuscular junction,NMJ)处,阻断神经递质乙酰胆碱的释放致使动物肌肉麻痹、呼吸衰竭直至死亡。SPANs与突触前膜特异性结合,水解膜磷脂生成溶血磷脂(Lysophospholipids,LysoPC)和脂肪酸(Fatty acids,FA),改变膜构象、膜通透性提高导致Ca2+大量内流至神经末梢、突触囊泡(Synaptic vesicles,SV)枯竭、线粒体功能障碍等。对蛇毒突触前磷脂酶A2神经毒素的受体分子及其引发的一系列胞内分子事件进行综述。

关键词(KeyWords)： 蛇毒;磷脂酶A2;突触前神经毒素;分子机制

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(30870303);; 陕西省自然科学基金(SJ08-C102)

作者(Author): 马兆瑞;王振;马亚瑞;何宇;杨章民;

Email:

DOI: 10.13989/j.cnki.0517-6611.2012.13.074

参考文献(References)：

• [1]ROSSETTO O,MONTECUCCO C.Presynaptic neurotoxins with enzymaticactivities[J].Handb Exp Pharmacol,2008,184:129-170.
• [2]PETAN T,KRIZAJ I,PUNGERCAR J.Restoration of enzymatic activity ina Ser-49 phospholipase A2 homologue decreases its Ca2+-independentmembrane damaging activity and increases its toxicity[J].Biochemistry,2007,46(44):12795-12809.
• [3]GUTIERREZ J M,PONCESOTO L A,MARANGONI S,et al.Systemic andlocal myotoxicity induced by snake venom group II phospholipases A2:comparison between crotoxin,crotoxin B and a Lys49 PLA2 homologues[J].Toxicon,2008,51(1):80-92.
• [4]LAMBEAU G,BARHANIN J,SCHWEITZ H,et al.Identification and prop-erties of very high affinity brain membrane-binding sites for a neurotoxicphospholipase from the taipan venom[J].J Biol Chem,1989,264:11503-11510.
• [5]TZENG M C,YEN C H,TSAI M D.Binding proteins on synaptic mem-branes for certain phospholipases A2 with presynaptic toxicity[J].Adv ExpMed Biol,1996,391:271-278.
• [6]KRIZAJ I,FAURE G,GUBENSEK F,et al.Neurotoxic phospholipases A2ammodytoxin and crotoxin bind to distinct high-affinity protein acceptors inTorpedo marmorata electric organ[J].Biochemistry,1997,36:2779-2787.
• [7]LAMBEAU G,SCHMID A,LAZDUNSKI M,et al.Identification and purifi-cation of a very high affinity binding protein for toxic phospholipases A2 inskeletal muscle[J].J Biol Chem,1990,265:9526-9532.
• [8]VARDJAN N,SHERMAN N E,PUNGERCAR J,et al.High molecularmass receptors for ammodytoxin in pig are tissue-specific isoforms of M-type phospholipase A2 receptor[J].Biochem Biophys Res Commun,2001,289:143-149.
• [9]SCHMIDT R R,BEZT H.Theβ-bungarotoxin-binding protein from chickbrain:binding sites for different neuronal K+channel ligands cofractionateupon partial purification[J].FEBS Lett,1988,240(1/2):65-70.
• [10]SCOTT V E S,PARCEJ D N,KEEN J N,et al.α-Dendrotoxin acceptorfrom bovine brain is a K+channel protein[J].J Biol Chem,1990,265:20094-20097.
• [11]Van VACTOR D,WALL D P,JOHNSON K G.Heparan sulfate proteogly-cans and the emergence of neuronal connectivity[J].Curr Opin Neurobi-ol,2006,16:40-51.
• [12]MURAKAMI M,KAMBE T,SHIMBARA S,et al.Functional association oftype IIA secretory phospholipase A2 with the glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan in cyclooxygenase-2-mediateddelayed prostanoid biosynthetic pathway[J].J Biol Chem,1999,274:227-236.
• [13]HARRIS J B,GRUBB B D,MALTIN C A,et al.The neurotoxicity of thevenom phospholipases A2,notexin and taipoxin[J].Exp Neurol,2000,161:517-526.
• [14]PUNGERCAR J,KRIZAJ I.Understanding the molecular mechanism un-derlying the presynaptic toxicity of secreted phospholipases A2[J].Toxi-con,2007,50(7):871-892.
• [15]RIGONI M,PIZZO P,SCHIAVO G,et al.Calcium influx and mitochondri-al alterations at synapses exposed to snake neurotoxins or their phospho-lipid hydrolysis products[J].J Biol Chem,2007,282:11238-11245.
• [16]PRASARNPUN S,WALSH J,HARRIS J B.β-bungarotoxin induced de-pletion of SVs at the mammalian neuromuscular junction[J].Neurophar-macology,2004,47:304-314.
• [17]GUTIRREZ J M,OWNBY C L.Skeletal muscle degeneration induced byvenom phospholipases A2:insights into the mechanisms of local and sys-temic myotoxicity[J].Toxicon,2003,42:915-931.
• [18]BERTIPAGLIA I,CARAFOLI E.Calpains and human disease[J].SubcellBiochem,2007,45:29-53.
• [19]BERNARDI P,RASOLA A.Calcium and cell death:the mitochondrialconnection[J].Subcell Biochem,2007,45:481-506.
• [20]MONTECUCCO C,GUTIRREZ J M,LOMONTE B.Cellular pathologyinduced by snake venom phospholipase A2 myotoxins and neurotoxins:common aspects of their mechanisms of action[J].Cell Mol Life Sci,2008,65(18):2897-2912.
• [21]MOUNIER C,FRANKEN P A,VERHEU H M,et al.The anticoagulanteffect of the human secretory phospholipase A2 on blood plasma and on acell-free system is due to a phospholipid-independent mechanism of ac-tion involving the inhibition of factor[J].Va Eur J Biochem,1996,237:778-785.
• [22]NECO P,ROSSETTO O,GIL A,et al.Taipoxin induces F-actin fragmen-tation and enhances release of catecholamines in bovine chromaffin cells[J].J Neurochem,2003,85:329-337.
• [23]MONTECUCCO C,ROSSETTO O,SCHIAVO G.Presynaptic receptor ar-rays for clostridial neurotoxins[J].Trends Microbiol,2004,12:442-446.
• [24]CACCIN P,RIGONI M,BISCEGLIE A,et al.Reversible skeletal neuro-muscular paralysisinduced by different lysophospholipids[J].FEBS Lett,2006,580:6317-6321.
• [25]PRAZNIKAR Z J,PETAN T,PUNGERCAR J.A neurotoxic secretoryphospholipase A2 induces apoptosis in motoneuron-like cells[J].Ann NYAcad Sci,2009,11(52):215-224.
• [26]LOGONDER U,PRAZNIKAR J Z,DAVEY S T,et al.Ultrastructural evi-dence for the uptake of a neurotoxic snake venom phospholipase A2 intomammalian motor nerve terminals[J].Exp Neurol,2009,219(2):591-594.
• [27]RIGONI M,CACCIN P,GSCHMEISSNER S,et al.Equivalent effects ofsnake PLA2 neurotoxins and lysophospholipid-fatty acid mixtures[J].Sci-ence,2005,310(5754):1678-1680.
• [28]BONANOMI D,PENNUTO M,RIGONI M,et al.Taipoxin induces synap-tic vesicle exocytosis and disrupts the interaction of synaptophysin I withVAMP2[J].Mol Pharmacol,2005,67:1901-1908.
• [29]BERNARDI P,PENZO D,WOJTCZAK L.Mitochondrial energy dissipa-tion by fatty acids,mechanisms and implications for cell death[J].VitamHorm,2002,65:97-126.
• [30]RIGONI M,PAOLI M,MILANESI E,et al.Snake phospholipase A2 neuro-toxins enter neurons,and specifically to mitochondria,and oper their tran-sition pores[J].J Biol Chem,2008,283(49):34013-34020.