Morphological changes induced by crotoxin in murine nerve and neuromuscular junction

Gopalakrishnakone, P.; Hawgood, Barbara J.

doi:10.1016/0041-0101(84)90162-4

Cited by 54 publications

(32 citation statements)

References 12 publications

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“…Interestingly, these findings closely match those seen by electron microscopy at intoxicated NMJs, which appear swollen, depleted of SVs and enriched in clathrin-coated invaginations of the plasma membrane representing incomplete SV retrieval (Chen and Lee, 1970;Cull-Candy et al, 1976;Gopalakrishnakone and Hawgood, 1984). It was recently proposed that fusion of synaptic vesicles could be induced by a vesicle-based PLA2 activity of the SPANs (Montecucco and Rossetto, 2000).…”

Section: Discussionsupporting

confidence: 68%

Snake presynaptic neurotoxins with phospholipase A2 activity induce punctate swellings of neurites and exocytosis of synaptic vesicles

Rigoni

Schiavo

Weston

et al. 2004

Journal of Cell Science

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The mechanisms of action of four snake presynaptic phospholipase A2 neurotoxins were investigated in cultured neurons isolated from various parts of the rat brain. Strikingly, physiological concentrations of notexin, β-bungarotoxin, taipoxin or textilotoxin induced a dose-dependent formation of discrete bulges at various sites of neuronal projections. Neuronal bulging was paralleled by the redistribution of the two synaptic vesicle markers synaptophysin I (SypI) and vesicle-attached membrane protein 2 (VAMP2) to the bulges, and by the exposure of the luminal domain of synaptotagmin on the cell surface. These neurotoxins induced glutamate release from cultured neurons similarly to the known evoked release of acetylcholine from neuromuscular junctions. In addition, partial fragmentation of F-actin and neurofilaments was observed in neurons, but not in astrocytes. These findings indicate that these snake presynaptic neurotoxins act with by same mechanism and that the observed phenotype results from the fusion of synaptic vesicles with the plasma membrane not balanced by an adequate membrane retrieval. These changes closely resemble those occurring at neuromuscular junctions of intoxicated animals and fully qualify these primary neuronal cultures as pertinent models for studying the molecular mode of action of these neurotoxins.

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Section: Discussionsupporting

confidence: 68%

Snake presynaptic neurotoxins with phospholipase A2 activity induce punctate swellings of neurites and exocytosis of synaptic vesicles

Rigoni

Schiavo

Weston

et al. 2004

Journal of Cell Science

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“…Whereas some consequences of C. d. terrificus venom have been extensively studied -such as myonecrosis (12)(13)(14)(15)(16)(17), coagulation disturbances (7,8,(18)(19)(20), neuromuscular effects (21,22), renal involvements (14,23) and homeostatic problems (20) -considerably less attention has been paid to its effects on the liver.…”

Section: Introductionmentioning

confidence: 99%

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

França¹,

Ferrari²,

Souza³

et al. 2009

J. Venom. Anim. Toxins incl. Trop. Dis

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Venom of the South American rattlesnake, Crotalus durissus terrificus (Cdt), presents myotoxic and neurotoxic outcomes, but reports on its effects on the liver are scarce. This study examined the hepatotoxicity resulting from Cdt venom administration (100, 200 and 300 μg/kg) in male Wistar rats. Animals were studies at 3, 6, 9 and 12 hours after venom injection. The hepatotoxicity was assessed through serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirrubin and also by histopathological evaluation. All the different concentrations of Cdt venom resulted in increased levels of hepatic enzymes, when compared with the control group, except for the 100 μg/kg dose, which presented normal levels at 9 and 12 hours after venom administration. Bilirrubin levels remained unchanged by Cdt venom. Histological analysis revealed endothelial damage, inflammatory cell infiltration, as well as sinusoidal and portal congestion. Based on these observations, we may conclude that Cdt venom causes dose-and time-dependent hepatic damage in rats, characterized by elevated hepatic enzyme levels and histological alterations.

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“…Much attention has been recently dedicated to a class of neurotoxins with phospholipase A2 (PLA2) 2 activity that are produced by different families of poisonous snakes (SPANs), whose precise biochemical and cellular mode of action has long remained elusive (2). A hallmark of their action in vivo and in vitro is the induction of enlargement of nerve terminals with large depletion of their content of synaptic vesicles (SV) (3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Calcium Influx and Mitochondrial Alterations at Synapses Exposed to Snake Neurotoxins or Their Phospholipid Hydrolysis Products

Rigoni¹,

Pizzo²,

Schiavo

et al. 2007

Journal of Biological Chemistry

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Snake presynaptic phospholipase A2 neurotoxins (SPANs) bind to the presynaptic membrane and hydrolyze phosphatidylcholine with generation of lysophosphatidylcholine (LysoPC) and fatty acid (FA). The LysoPC ؉ FA mixture promotes membrane fusion, inducing the exocytosis of the ready-to-release synaptic vesicles. However, also the reserve pool of synaptic vesicles disappears from nerve terminals intoxicated with SPAN or LysoPC ؉ FA. Here, we show that LysoPC ؉ FA and SPANs cause a large influx of extracellular calcium into swollen nerve terminals, which accounts for the extensive synaptic vesicle release. This is paralleled by the change of morphology and the collapse of membrane potential of mitochondria within nerve bulges. These results complete the picture of events occurring at nerve terminals intoxicated by SPANs and define the LysoPC ؉ FA lipid mixture as a novel and effective agonist of synaptic vesicle release.

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Morphological changes induced by crotoxin in murine nerve and neuromuscular junction

Cited by 54 publications

References 12 publications

Snake presynaptic neurotoxins with phospholipase A2 activity induce punctate swellings of neurites and exocytosis of synaptic vesicles

Snake presynaptic neurotoxins with phospholipase A2 activity induce punctate swellings of neurites and exocytosis of synaptic vesicles

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

Calcium Influx and Mitochondrial Alterations at Synapses Exposed to Snake Neurotoxins or Their Phospholipid Hydrolysis Products

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