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Reversible skeletal neuromuscular paralysis induced by different lysophospholipids
Authors:Caccin Paola  Rigoni Michela  Bisceglie Alessandra  Rossetto Ornella  Montecucco Cesare
Affiliation:Dipartimento di Scienze Biomediche, Istituto C.N.R. Neuroscienze, Università di Padova, Viale G. Colombo n. 3, 35121 Padova, Italy.
Abstract:Lysophosphatidylcholine rapidly paralyses the neuromuscular junction (NMJ), similarly to snake phospholipase A2 neurotoxins, implicating a lipid hemifusion-pore transition in neuroexocytosis. The mode and kinetics of NMJ paralysis of different lysophospholipids (lysoPLs) in high or low [Mg2+] was investigated. The following order of potency was found: lysophosphatidylcholine>lysophosphatidylethanolamine>lysophosphatidic acid>lysophosphatidylserine>lysophosphatidylglycerol. The latter two lysoPLs closely mimic the profile of paralysis caused by the toxins in high [Mg2+]. This paralysis is fully reversed by albumin washing. These findings provide novel insights on the mode of action of snake neurotoxins and qualify lysoPLs as novel agents to study neuroexocytosis.
Keywords:FA, fatty acids   OA, oleic acid   SPAN, snake phospholipase A2 presynaptic neurotoxin   lysoPC, lysophosphatidylcholine   lysoPE, lysophosphatidylethanolamine   lysoPS, lysophosphatidylserine   lysoPG, lysophosphatidylglycerol   lysoPA, lysophosphatidic acid   lysoPL, lysophospholipid   SVs, synaptic vesicles   [Mg2+], magnesium concentration   PLA2, phospholipase A2   neuromuscular junction, NMJ
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