Antimicrobial peptides from scorpion venom induce Ca2+ signaling in HL-60 cells

Moerman, Leentje; Verdonck, Fons; Willems, Jean; Tytgat, Jan; Bosteels, Suzanne

doi:10.1016/j.bbrc.2003.09.175

Cited by 19 publications

(13 citation statements)

References 39 publications

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“…PI value of this domain in the BPP clade approached 10.5. As these toxins have been shown to be lethal and synergistically enhance the excitatory effects of CSα/β ion channel-specific neurotoxins by interaction with the neuronal membranes [25,26,75,76,77,78,79], we consider any antimicrobial activity attributed to them in laboratory investigations (but without supporting natural history data) to be an incidental activity as a consequence of the powerful cytotoxicity, rather than an evolutionarily selected activity. This is in contrast to the alpha-helical frog antimicrobial peptides which play a protective role on the moist skin of frog, which is constantly targeted by microbial infections [80].…”

Section: Resultsmentioning

confidence: 99%

Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds

Sunagar

Undheim

Chan

et al. 2013

Toxins

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The episodic nature of natural selection and the accumulation of extreme sequence divergence in venom-encoding genes over long periods of evolutionary time can obscure the signature of positive Darwinian selection. Recognition of the true biocomplexity is further hampered by the limited taxon selection, with easy to obtain or medically important species typically being the subject of intense venom research, relative to the actual taxonomical diversity in nature. This holds true for scorpions, which are one of the most ancient terrestrial venomous animal lineages. The family Buthidae that includes all the medically significant species has been intensely investigated around the globe, while almost completely ignoring the remaining non-buthid families. Australian scorpion lineages, for instance, have been completely neglected, with only a single scorpion species (Urodacus yaschenkoi) having its venom transcriptome sequenced. Hence, the lack of venom composition and toxin sequence information from an entire continent’s worth of scorpions has impeded our understanding of the molecular evolution of scorpion venom. The molecular origin, phylogenetic relationships and evolutionary histories of most scorpion toxin scaffolds remain enigmatic. In this study, we have sequenced venom gland transcriptomes of a wide taxonomical diversity of scorpions from Australia, including buthid and non-buthid representatives. Using state-of-art molecular evolutionary analyses, we show that a majority of CSα/β toxin scaffolds have experienced episodic influence of positive selection, while most non-CSα/β linear toxins evolve under the extreme influence of negative selection. For the first time, we have unraveled the molecular origin of the major scorpion toxin scaffolds, such as scorpion venom single von Willebrand factor C-domain peptides (SV-SVC), inhibitor cystine knot (ICK), disulphide-directed beta-hairpin (DDH), bradykinin potentiating peptides (BPP), linear non-disulphide bridged peptides and antimicrobial peptides (AMP). We have thus demonstrated that even neglected lineages of scorpions are a rich pool of novel biochemical components, which have evolved over millions of years to target specific ion channels in prey animals, and as a result, possess tremendous implications in therapeutics.

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Section: Resultsmentioning

confidence: 99%

Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds

Sunagar

Undheim

Chan

et al. 2013

Toxins

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“…They facilitate the activity of the neurotoxins and at the same time protect the venom duct and glands against bacterial invasion by membrane disturbance and pore building. Additionally, antimicrobial peptides may also modulate intracellular signaling by increasing intracellular Ca 2ϩ , as reported for parabutoporin and opistoporin from scorpion venoms (39). Simultaneously, the inhibition of ion channels by the neurotoxins is further enhanced by the high K ϩ ion concentration in the venom, shifting the K ϩ equilibrium potential (34).…”

Section: Discussionmentioning

confidence: 99%

CSTX-13, a highly synergistically acting two-chain neurotoxic enhancer in the venom of the spiderCupiennius salei(Ctenidae)

Wullschleger

Kuhn‐Nentwig

Tromp

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The survival of the spider Cupiennius salei depends on its hunting success, which largely relies on its immediately paralyzing multicomponent venom. Here, we report on the isolation and characterization of CSTX-13, a neurotoxic enhancer in the spider venom. De novo elucidation of the disulfide bridge pattern of CSTX-13 and the neurotoxin CSTX-1 by tandem MS revealed an identical arrangement. However, in contrast to CSTX-1, CSTX-13 is a two-chain peptide with two interchain and two intrachain disulfide bridges. Furthermore, the insecticidal activity of CSTX-13 is synergistically increased in the presence of K ؉ ions as well as of the cytolytic peptide cupiennin 1a. We demonstrated that the weakly neurotoxic CSTX-13 enhances the paralytic activity of the neurotoxin CSTX-1 by 65% when it is administered with the latter at its entirely nontoxic physiological concentration, which is 440 times below its LD50 concentration.

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“…Both peptides are capable of inducing a reversible release of Ca 2þ from the intracellular stores of Ca 2þ of granulocyte-like HL60 cells. The release of calcium was sensitive to Pertussis toxin, indicating that the release of Ca 2þ involves G proteins (Moerman et al, 2003). It has been shown that parabutoporin inhibits the activation of the NADPH oxidase by acting as a competitive inhibitor of Protein Kinase B (Akt), thus contributing to the decline of superoxide production by human neutrophils (Remijsen et al, 2006).…”

Section: Immuno-modulatorsmentioning

confidence: 99%

Scorpion venom components as potential candidates for drug development

Ortíz

Gurrola

Schwartz

et al. 2015

Toxicon

273

218

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Scorpions are well known for their dangerous stings that can result in severe consequences for human beings, including death. Neurotoxins present in their venoms are responsible for their toxicity. Due to their medical relevance, toxins have been the driving force in the scorpion natural compounds research field. On the other hand, for thousands of years, scorpions and their venoms have been applied in traditional medicine, mainly in Asia and Africa. With the remarkable growth in the number of characterized scorpion venom components, several drug candidates have been found with the potential to tackle many of the emerging global medical threats. Scorpions have become a valuable source of biologically active molecules, from novel antibiotics to potential anticancer therapeutics. Other venom components have drawn attention as useful scaffolds for the development of drugs. This review summarizes the most promising candidates for drug development that have been isolated from scorpion venoms.

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Antimicrobial peptides from scorpion venom induce Ca2+ signaling in HL-60 cells

Cited by 19 publications

References 39 publications

Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds

Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds

CSTX-13, a highly synergistically acting two-chain neurotoxic enhancer in the venom of the spiderCupiennius salei(Ctenidae)

Scorpion venom components as potential candidates for drug development

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