Suramin protects the murine motor nerves from the toxic effects of presynaptic Ca 2+ channel inhibitors

Lin, Min-Jon; Tan, Ching-Ting; Lee, Shiann-Yann; Lin‐Shiau, Shoei‐Yn

doi:10.1016/s0304-3940(00)01136-8

Cited by 2 publications

(2 citation statements)

References 12 publications

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“…The mechanism of action of suramin at the neuromuscular junction remains unclear, but it is known that suramin blockades presynaptic voltage-dependent Ca 2+ channels on the motor nerve terminal, reducing the release of acetylcholine (Henning et al, 1996;Lin et al, 2000). However, this mode of Superposition of the dimeric MjTX-II-suramin and the Ser49-PLA 2 escarpholin S-suramin structures.…”

Section: Myotoxic Activity Of Mjtx-ii Is Neutralized By Suraminmentioning

confidence: 99%

Structural and functional evidence for membrane docking and disruption sites on phospholipase A₂-like proteins revealed by complexation with the inhibitor suramin

Marchi-Salvador

Dreyer

Cavalcante

et al. 2015

Acta Crystallogr D Biol Crystallogr

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Local myonecrosis resulting from snakebite envenomation is not efficiently neutralized by regular antivenom administration. This limitation is considered to be a significant health problem by the World Health Organization. Phospholipase A 2 -like (PLA 2 -like) proteins are among the most important proteins related to the muscle damage resulting from several snake venoms. However, despite their conserved tertiary structure compared with PLA 2 s, their biological mechanism remains incompletely understood. Different oligomeric conformations and binding sites have been identified or proposed, leading to contradictory data in the literature. In the last few years, a comprehensive hypothesis has been proposed based on fatty-acid binding, allosteric changes and the presence of two different interaction sites. In the present study, a combination of techniques were used to fully understand the structuralfunctional characteristics of the interaction between suramin and MjTX-II (a PLA 2 -like toxin). In vitro neuromuscular studies were performed to characterize the biological effects of the protein-ligand interaction and demonstrated that suramin neutralizes the myotoxic activity of MjTX-II. The high-resolution structure of the complex identified the toxin-ligand interaction sites. Calorimetric assays showed two different binding events between the protein and the inhibitor. It is demonstrated for the first time that the inhibitor binds to the surface of the toxin, obstructing the sites involved in membrane docking and disruption according to the proposed myotoxic mechanism. Furthermore, higher-order oligomeric formation by interaction with interfacial suramins was observed, which may also aid the inhibitory process. These results further substantiate the current myotoxic mechanism and shed light on the search for efficient inhibitors of the local myonecrosis phenomenon.

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Section: Myotoxic Activity Of Mjtx-ii Is Neutralized By Suraminmentioning

confidence: 99%

Structural and functional evidence for membrane docking and disruption sites on phospholipase A₂-like proteins revealed by complexation with the inhibitor suramin

Marchi-Salvador

Dreyer

Cavalcante

et al. 2015

Acta Crystallogr D Biol Crystallogr

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“…Suramin significantly delays the time to paralysis induced by -bungarotoxin in mice when administered intravenously 30min before injecting the toxin and delays the blocking of transmitter release in-vitro [14]. In 2000, Lin and colleagues reported that suramin protected the murine motor nerves from the toxic effects of the presynaptic Ca +2 channel inhibitor, omega-conotoxin MVIIC and omega-agatoxin IVA, and reduced their depressant effects on muscle contraction [16].…”

Section: Introductionmentioning

confidence: 99%

Antagonistic Effects of Suramin Against the Venom of Snake, Echis Carinatus, on the Circulatory System of Developing Chicken Embryos

Hajari

Fathi

Saadatfar

et al. 2019

IJT

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Background: The snake, Echis carinatus, one of the most venomous snakes in Asia, possesses a deadly hemotoxic venom. It has been reported that suramin, an anti-trypansomiasis drug, can inhibit the toxic effects of some snake venoms. This study was conducted to evaluate the possible antagonistic effects of suramin against the hemorrhagic activity of the venom from an Iranian snake, Echis carinatus, in developing chicken embryos. Methods: One day old fertile eggs (n=250) were incubated for six days at 37ºC and 60% humidity. Paper discs (5 mm diameter) containing different concentrations of E. carinatus venom (5, 10, 20 & 30 μg) were placed on the chorioallantoic membrane over the major bilateral vein and were left in place until hemorrage occurred and the embryos died. Results: We found the standard hemorrhagic dose (SHD) of E. carinatus venom to be (5 μg/disc). Various concentrations (5, 10 & 20 μg) of suramin were tested against SHD of E. carinatus venom in different protocols. Control experiments were performed with the buffered saline solution, venom and suramin individually. The results demonstrated that suramin at 5, 10 and 20 μg significantly (P<0.05) delayed time to death (717, 521 & 208 min) of embryos poisoned with E. carinatus venom in a dose-dependent manner. Conclusion: Suramin exerted protective and inhibitory effects against the deadly E. carinatus venom, and therefore, may potentially offer future therapeutic applications against poisoning with E. carinatus venom.

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Suramin protects the murine motor nerves from the toxic effects of presynaptic Ca 2+ channel inhibitors

Cited by 2 publications

References 12 publications

Structural and functional evidence for membrane docking and disruption sites on phospholipase A₂-like proteins revealed by complexation with the inhibitor suramin

Structural and functional evidence for membrane docking and disruption sites on phospholipase A₂-like proteins revealed by complexation with the inhibitor suramin

Antagonistic Effects of Suramin Against the Venom of Snake, Echis Carinatus, on the Circulatory System of Developing Chicken Embryos

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Suramin protects the murine motor nerves from the toxic effects of presynaptic Ca 2+ channel inhibitors

Cited by 2 publications

References 12 publications

Structural and functional evidence for membrane docking and disruption sites on phospholipase A2-like proteins revealed by complexation with the inhibitor suramin

Structural and functional evidence for membrane docking and disruption sites on phospholipase A2-like proteins revealed by complexation with the inhibitor suramin

Antagonistic Effects of Suramin Against the Venom of Snake, Echis Carinatus, on the Circulatory System of Developing Chicken Embryos

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Structural and functional evidence for membrane docking and disruption sites on phospholipase A₂-like proteins revealed by complexation with the inhibitor suramin

Structural and functional evidence for membrane docking and disruption sites on phospholipase A₂-like proteins revealed by complexation with the inhibitor suramin