Parabutoporin—an antibiotic peptide from scorpion venom—can both induce activation and inhibition of granulocyte cell functions

Moerman, Leentje; Bosteels, Suzanne; Bruyneel, Erik; Ryniers, Filip; Verdonck, Fons

doi:10.1016/j.peptides.2004.04.008

Cited by 22 publications

(21 citation statements)

References 18 publications

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“…The production of superoxide by the NADPH oxidase in PMA stimulated granulocytes is inhibited to 90% (99%) in the presence of 0.2 lM (0.5 lM) L-Cu1a. This inhibition occurs in about the same concentration range as reported for parabutoporin and opistoporin, cationic pore forming peptides isolated from the venom of South African scorpions (Willems et al 2002(Willems et al , 2004. The latter are also chemotactic for granulocytes but, in contrast to these results, no induction of a granulocyte chemotactic response could be observed with L-Cu1a in concentrations between 0.2 and 0.8 lM.…”

Section: Effects Of L-cu1a On Different Human Cellssupporting

confidence: 69%

Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity on bacteria, protozoan parasites, insects, and human cancer cells

et al. 2010

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Cupiennin 1a, a cytolytic peptide isolated from the venom of the spider Cupiennius salei, exhibits broad membranolytic activity towards bacteria, trypanosomes, and plasmodia, as well as human blood and cancer cells. In analysing the cytolytic activity of synthesised all-D-and all-L-cupiennin 1a towards pro-and eukaryotic cells, a stereospecific mode of membrane destruction could be excluded. The importance of negatively charged sialic acids on the outer leaflet of erythrocytes for the binding and haemolytic activity of L-cupiennin 1a was demonstrated. Reducing the overall negative charges of erythrocytes by partially removing their sialic acids or by protecting them with tri-or pentalysine results in reduced haemolytic activity of the peptide.

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Section: Effects Of L-cu1a On Different Human Cellssupporting

confidence: 69%

Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity on bacteria, protozoan parasites, insects, and human cancer cells

et al. 2010

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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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“…Confocal microscopy analysis revealed that FITC-labeled PP colocalizes considerably with GM1-ganglioside, a marker for lipid rafts [18]. We next investigated whether the accumulation of PP in lipid rafts is of relevance for its observed bio-effects on neutrophils, i.e., inhibition of stimulated NADPH oxidase activity and prosurvival effects.…”

Section: The Prosurvival Effect Of Pp Depends On Intact Lipid Raftsmentioning

confidence: 99%

“…From the scorpion venom of Parabuthus schlechteri, we have isolated and characterized a potent NADPH oxidase inhibitor, parabutoporin (PP) [18]. At micromolar concentrations, it was initially shown to have antimicrobial properties, but in the same concentration range, it also appeared to induce pore formation in human cells, including neutrophils [19].…”

Section: Introductionmentioning

confidence: 99%

“…At micromolar concentrations, it was initially shown to have antimicrobial properties, but in the same concentration range, it also appeared to induce pore formation in human cells, including neutrophils [19]. However, at submicromolar concentrations, PP is nonlytic [18,20]. Of interest, activation of NADPH oxidase with PMA and fMLP is strongly inhibited by PP at nonlytic concentrations.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation of Akt

Remijsen

Berghe

Parthoens

et al. 2008

Journal of Leukocyte Biology

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Neutrophil cell death plays a crucial role in neutrophil homeostasis and the resolution of inflammation. The superoxide-producing NADPH oxidase is involved in pathogen degradation and subsequent activation of cell death programs. Neutrophils from patients with chronic granulomatous disease, who have a deficient NADPH oxidase activity, have been demonstrated previously to have a prolonged lifespan, suggesting that a basal NADPH oxidase activity also regulates spontaneous neutrophil turnover. The NADPH oxidase inhibitor parabutoporin (PP) does delay spontaneous apoptosis, but this effect is completely independent of NADPH oxidase inhibition. Instead, the prosurvival effect of PP depends on activation of protein kinase B/Akt via lipid raft signaling. Disruption of lipid rafts abrogates the prosurvival effect without interfering with NADPH oxidase activity. Furthermore, we cannot detect a different rate of spontaneous apoptosis between normal and NADPH oxidase-deficient neutrophils, arguing against a role of NADPH oxidase in spontaneous neutrophil apoptosis.

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Parabutoporin—an antibiotic peptide from scorpion venom—can both induce activation and inhibition of granulocyte cell functions

Cited by 22 publications

References 18 publications

Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity on bacteria, protozoan parasites, insects, and human cancer cells

Cupiennin 1a exhibits a remarkably broad, non-stereospecific cytolytic activity on bacteria, protozoan parasites, insects, and human cancer cells

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

Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation of Akt

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