Mass spectrometry analysis of the phospholipase A activity of snake pre-synaptic neurotoxins in cultured neurons
Mass spectrometry analysis of the phospholipase A activity of snake pre-synaptic neurotoxins in cultured neurons
Snake pre-synaptic phospholipase A(2) neurotoxins paralyse the neuromuscular junction by releasing phospholipid hydrolysis products that alter curvature and permeability of the pre-synaptic membrane. Here, we report results deriving from the first chemical analysis of the action of these neurotoxic phospholipases in neurons, made possible by the use of high sensitivity mass spectrometry. The time-course of the phospholipase A(2) activity (PLA(2)) hydrolysis of notexin, beta-bungarotoxin, taipoxin and textilotoxin acting in cultured neurons was determined. At variance from their enzymatic activities in vitro, these neurotoxins display comparable kinetics of lysophospholipid release in neurons, reconciling the large discrepancy between their in vivo toxicities and their in vitro enzymatic activities. The ratios of the lyso derivatives of phosphatidyl choline, ethanolamine and serine obtained here together with the known distribution of these phospholipids among cell membranes, suggest that most PLA(2) hydrolysis takes place on the cell surface. Although these toxins were recently shown to enter neurons, their intracellular hydrolytic action and the activation of intracellular PLA(2)s appear to contribute little, if any, to the phospholipid hydrolysis measured here
lysophospholipids, phospholipase A2 activity, snake neurotoxins, toxicity
737-744
Paoli, Marco
11abf4db-25f0-4f6a-ba5f-7180d6c36b87
Rigoni, Michela
f9adfe5a-3246-481c-b5e6-ccf5e6f45d66
Koster, Grielof
e404c38a-6f48-430a-adf0-5208228cb9e7
Rossetto, Ornella
01dad575-df44-445d-b481-a0eb9352bb6f
Montecuccu, Cesare
e96dfc89-a1ce-470a-b67e-4db7152e8a53
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
November 2009
Paoli, Marco
11abf4db-25f0-4f6a-ba5f-7180d6c36b87
Rigoni, Michela
f9adfe5a-3246-481c-b5e6-ccf5e6f45d66
Koster, Grielof
e404c38a-6f48-430a-adf0-5208228cb9e7
Rossetto, Ornella
01dad575-df44-445d-b481-a0eb9352bb6f
Montecuccu, Cesare
e96dfc89-a1ce-470a-b67e-4db7152e8a53
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Paoli, Marco, Rigoni, Michela, Koster, Grielof, Rossetto, Ornella, Montecuccu, Cesare and Postle, Anthony D.
(2009)
Mass spectrometry analysis of the phospholipase A activity of snake pre-synaptic neurotoxins in cultured neurons.
Journal of Neurochemistry, 111 (3), .
(doi:10.1111/j.1471-4159.2009.06365.x).
Abstract
Snake pre-synaptic phospholipase A(2) neurotoxins paralyse the neuromuscular junction by releasing phospholipid hydrolysis products that alter curvature and permeability of the pre-synaptic membrane. Here, we report results deriving from the first chemical analysis of the action of these neurotoxic phospholipases in neurons, made possible by the use of high sensitivity mass spectrometry. The time-course of the phospholipase A(2) activity (PLA(2)) hydrolysis of notexin, beta-bungarotoxin, taipoxin and textilotoxin acting in cultured neurons was determined. At variance from their enzymatic activities in vitro, these neurotoxins display comparable kinetics of lysophospholipid release in neurons, reconciling the large discrepancy between their in vivo toxicities and their in vitro enzymatic activities. The ratios of the lyso derivatives of phosphatidyl choline, ethanolamine and serine obtained here together with the known distribution of these phospholipids among cell membranes, suggest that most PLA(2) hydrolysis takes place on the cell surface. Although these toxins were recently shown to enter neurons, their intracellular hydrolytic action and the activation of intracellular PLA(2)s appear to contribute little, if any, to the phospholipid hydrolysis measured here
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Published date: November 2009
Keywords:
lysophospholipids, phospholipase A2 activity, snake neurotoxins, toxicity
Organisations:
Infection Inflammation & Immunity
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Local EPrints ID: 72683
URI: http://eprints.soton.ac.uk/id/eprint/72683
ISSN: 0022-3042
PURE UUID: e94ba5a7-b6d8-4f96-8e12-f14c789f2a01
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Date deposited: 19 Feb 2010
Last modified: 14 Mar 2024 02:31
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Author:
Marco Paoli
Author:
Michela Rigoni
Author:
Grielof Koster
Author:
Ornella Rossetto
Author:
Cesare Montecuccu
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