Suramin inhibits the toxic effects of presynaptic neurotoxins at the mouse motor nerve terminals

Lin‐Shiau, Shoei‐Yn; Lin, Min-Jon

doi:10.1016/s0014-2999(99)00544-0

Cited by 21 publications

(15 citation statements)

References 15 publications

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“…The other polypeptide chain B is a rather small subunit of 60 amino acid residues, showing sequence similarity to dendrotoxin and toxins I and K from mamba venom, which are representative of Kunitz protease inhibitor (Dufton, 1985). This toxin inhibits acetylcholine release from the motor nerve terminals (Halliwell and Dolly, 1982;Rowan et al, 1990;Lin-Shiau and Lin, 1999). In spite of previous efforts (Anderson and Parsons, 1986;Lin-Shiau and Fu, 1986;Rowan and Harvey, 1988), the mechanisms of the neuromuscular blocking activity of -BuTX are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Phospholipase A₂ activity of β‐bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons

Chen

2005

J. Neurobiol.

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The aim of this study was to investigate the mechanism of the cytotoxic effect of beta-bungarotoxin (beta-BuTX), a presynaptic neurotoxin, on rat cerebellar granule neurons (CGNs). The maturation of CGNs is characterized by the prominent dense neurite networks that became fragmented after treatment with beta-BuTX, and this cytotoxic effect of beta-BuTX on CGNs was in a dose- and time-dependant manner. The cytotoxic effect of beta-BuTX was found to be more potent than other toxins, such as alpha-BuTX, cardiotoxin, melittin, and Naja naja atra venom phospholipase A(2). Meanwhile, undifferentiated neuroblastoma neuronal cell lines, IMR-32 and SK-N-MC, and astrocytes were found to be resistant to beta-BuTX. These results indicated that only the mature CGNs were sensitive to beta-BuTX insults. None of the following chemicals: antioxidants, K(+)-channel activator, K(+)-channel antagonists, intracellular Ca(2+) chelator, Ca(2+)-channel blockers, NMDA receptor antagonists, and nitric oxide synthase inhibitor tested, were able to reduce beta-BuTX-induced cytotoxicity. However, secretory type phospholipase A(2) inhibitors (glycyrrhizin and aristolochic acid) and a free radical scavenger (5,5-dimethyl pyrroline N-oxide, DMPO) could attenuate not only beta-BuTX-induced cytotoxicity but also ROS production and caspase-3 activation. These data suggest that phospholipase A(2) activity of beta-BuTX may be responsible for free radical generation and caspase-3 activation that accounts for the observed cytotoxic effect. It is proposed that the CGNs can be a useful tool for studying interactions of the molecules on neuronal plasma membrane with beta-BuTX that mediates the specific cytotoxicity.

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Section: Introductionmentioning

confidence: 99%

Phospholipase A₂ activity of β‐bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons

Chen

2005

J. Neurobiol.

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“…58,2009 Suramin inhibits human group IIA phospholipase A 2 215 of snake venoms has revealed that suramin is an effective inhibitor of the neurotoxic effects of beta-bungarotoxin isolated from the venom of the Formosan Krait Bungarus multicintus. [25], and is an antagonist of the myotoxic activities of bothropstoxin-I [27] and Myotoxin-II [54], both of which are Lys49 PLA 2 s from the venoms of Bothrops jararacussu and B. asper respectively. The myotoxicity of Lys49-PLA 2 s is mediated by residues in the C-terminal loop region of the protein [55], and although independent of hydrolytic activity, evidence from site-directed mutagenesis indicates that occupancy of the substrate binding cleft plays a role in activation of the protein [56].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that suramin can inhibit the neuromuscular blockade induced by the PLA 2 component of several snake venoms including presynaptic neurotoxins such as beta-bungarotoxin and crotoxin [25]. Moreover, suramin prevents the development of muscle necrosis induced by some snake venoms, since it inhibits the myotoxic and in vitro neuromuscular blocking activities of Lys49 phospholipases A 2 from Bothrops species [26,27].…”

Section: Introductionmentioning

confidence: 99%

Suramin inhibits macrophage activation by human group IIA phospholipase A2, but does not affect bactericidal activity of the enzyme

et al. 2009

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“…Recent research has shown that the antitrypanosomiasis agent and P 2 receptor antagonist suramin inhibits the effects of presynaptic neurotoxins (Lin-Shiau and Lin, 1999). It also inhibits the myotoxins isolated from the venom of Bothrops species both in vitro and in vivo (Murakami et al, 2005).…”

Section: Neutralization Of Neurotoxicity By Other Agentsmentioning

confidence: 99%

“…Suramin is thought to prevent the inhibition of neurotransmitter release from the motor nerve terminals. This is evidenced by the delayed onset of neurotoxicity when applied both simultaneously with β-bungarotoxin, or after allowing sufficient time for toxin to bind presynaptic membrane receptors (Lin-Shiau and Lin, 1999). There are no published reports of suramin being tested against the effects of β-neurotoxins from the venoms of Australian and New Guinean snakes.…”

Section: Neutralization Of Neurotoxicity By Other Agentsmentioning

confidence: 99%

Neurotoxins From Australo-Papuan Elapids: A Biochemical and Pharmacological Perspective

Kuruppu

Smith

Hodgson

2008

Critical Reviews in Toxicology

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Most of the medically important snakes in Papua New Guinea and Australia belong to the family Elapidae and are referred to as "Australo-Papuan" elapids. Neurotoxicity is often a life-threatening symptom of envenoming by these snakes; therefore, much attention has been paid to the isolation and detailed pharmacological and biochemical characterization of the presynaptic (beta) and postsynaptic (alpha) neurotoxins from these elapid venoms. These studies have highlighted the potential for these toxins to be used as highly potent and selective probes for biomedical research and, perhaps, the potential for their use as lead compounds for the development of pharmaceutical agents. Historically, the potency of neurotoxins/crude venoms has been determined using murine LD50 (lethal dose) assays. However, a different rank order of potency often results when crude venoms/toxins are ranked based on their in vitro pharmacological parameters (e.g., t90 values). The lack of neurotoxicity following envenoming by brown snakes, despite the presence of a potent neurotoxin in their venom, has puzzled clinical toxinologists for years. This paradox also appears to include envenoming by the Stephen's banded snake. Lastly, the in vitro studies examining the effectiveness of antivenoms as well as the potential for alternative compounds to reverse/prevent neurotoxicity are discussed. This review presents for the first time a detailed comparative analysis of the pharmacology and biochemistry of neurotoxins isolated from the Australo-Papuan elapids, placing emphasis on the time taken for onset of action, receptor binding parameters, reversibility, and the methods for determining potency.

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Suramin inhibits the toxic effects of presynaptic neurotoxins at the mouse motor nerve terminals

Cited by 21 publications

References 15 publications

Phospholipase A₂ activity of β‐bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons

Phospholipase A₂ activity of β‐bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons

Suramin inhibits macrophage activation by human group IIA phospholipase A2, but does not affect bactericidal activity of the enzyme

Neurotoxins From Australo-Papuan Elapids: A Biochemical and Pharmacological Perspective

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Suramin inhibits the toxic effects of presynaptic neurotoxins at the mouse motor nerve terminals

Cited by 21 publications

References 15 publications

Phospholipase A2 activity of β‐bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons

Phospholipase A2 activity of β‐bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons

Suramin inhibits macrophage activation by human group IIA phospholipase A2, but does not affect bactericidal activity of the enzyme

Neurotoxins From Australo-Papuan Elapids: A Biochemical and Pharmacological Perspective

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Phospholipase A₂ activity of β‐bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons

Phospholipase A₂ activity of β‐bungarotoxin is essential for induction of cytotoxicity on cerebellar granule neurons