Mastoparan, a wasp venom, stimulates insulin release by pancreatic islets through pertussis toxin sensitive GTP-binding protein

doi:10.1016/0006-291X(89)92779-4

Biochemical and Biophysical Research Communications

Volume 158, Issue 3, 15 February 1989, Pages 712-716

https://doi.org/10.1016/0006-291X(89)92779-4 Get rights and content

Abstract

A wasp venom, mastoparan, rapidly stimulated insulin release by rat pancreatic islets in a dose-related manner. The amount of insulin released in response to 58 μM mastoparan far exceeded that induced by 27.8 mM glucose. Mastoparan stimulated insulin release to similar degrees at ambient glucose concentrations of 1.7 mM and 5.6 mM. The islets obtained from pertussis toxin-treated rats showed unequivocally less response to mastoparan. Pretreatment of islets with bromophenacyl bromide, a phospholipase A₂ inhibitor, abolished their responsiveness to mastoparan. Pretreatment of islets with nifedipine, a Ca²⁺ channel blocker, was without effect. Mastoparan is a unique stimulator of insulin release by the pancreatic islets, which acts through GTP-binding protein(s) and phospholipase A₂.

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Cited by (80)

Mastoparan induces apoptosis in B16F10-Nex2 melanoma cells via the intrinsic mitochondrial pathway and displays antitumor activity in vivo
2015, Peptides
Citation Excerpt :
Mastoparan is a 14-amino acid amphipathic and cationic peptide obtained from Vespula lewisii venom that has been studied over the past 30 years [9]. In addition to the extensively studied antimicrobial effects [35], early works by Hirai et al. [9], demonstrated that mastoparan exhibits potent exocytotic activity in a diversity of cell types including mast cells, pancreatic islet β-cells, platelets, chromaffin cells, and induces activation of phospholipase A2 and C [1,22,41]. More recently, it has been demonstrated that mastoparan and analogous peptides exert cytotoxic effects in tumorigenic cells [27,38,40].
Mastoparan is an α-helical and amphipathic tetradecapeptide obtained from the venom of the wasp Vespula lewisii. This peptide exhibits a wide variety of biological effects, including antimicrobial activity, increased histamine release from mast cells, induction of a potent mitochondrial permeability transition and tumor cell cytotoxicity. Here, the effects of mastoparan in malignant melanoma were studied using the murine model of B16F10-Nex2 cells. In vitro, mastoparan caused melanoma cell death by the mitochondrial apoptosis pathway, as evidenced by the Annexin V-FITC/PI assay, loss of mitochondrial membrane potential (ΔΨ_m), generation of reactive oxygen species, DNA degradation and cell death signaling. Most importantly, mastoparan reduced the growth of subcutaneous melanoma in syngeneic mice and increased their survival. The present results show that mastoparan induced caspase-dependent apoptosis in melanoma cells through the intrinsic mitochondrial pathway protecting the mice against tumor development.
The effects of the C-terminal amidation of mastoparans on their biological actions and interactions with membrane-mimetic systems
2014, Biochimica et Biophysica Acta - Biomembranes
Citation Excerpt :
Despite the importance of these studies, little extensive investigation has been performed focusing on the structure/activity relationship of mastoparan peptides. Structural and functional studies have always been isolated from each other; some functional investigations only assayed mast cell degranulation and/or leukocytes chemotaxis, which are mostly dependent on peptide–receptor (GPCRs) interaction [41,42]. Meanwhile, other studies have focused only on hemolytic action and/or antibiosis, which are dependent on peptide–phospholipid interaction [43,44], without investigating mast cell degranulation and PMNL chemotaxis.
Polycationic peptides may present their C-termini in either amidated or acidic form; however, the effects of these conformations on the mechanisms of interaction with the membranes in general were not properly investigated up to now. Protonectarina-MP mastoparan with an either amidated or acidic C-terminus was utilized to study their interactions with anionic and zwitterionic vesicles, using measurements of dye leakage and a combination of H/D exchange and mass spectrometry to monitor peptide–membrane interactions. Mast cell degranulation, hemolysis and antibiosis assays were also performed using these peptides, and the results were correlated with the structural properties of the peptides. The C-terminal amidation promotes the stabilization of the secondary structure of the peptide, with a relatively high content of helical conformations, permitting a deeper interaction with the phospholipid constituents of animal and bacterial cell membranes. The results suggested that at low concentrations Protonectarina-MP interacts with the membranes in a way that both terminal regions remain positioned outside the external surface of the membrane, while the α-carbon backbone becomes partially embedded in the membrane core and changing constantly the conformation, and causing membrane destabilization. The amidation of the C-terminal residue appears to be responsible for the stabilization of the peptide conformation in a secondary structure that is richer in α-helix content than its acidic congener. The helical, amphipathic conformation, in turn, allows a deeper peptide–membrane interaction, favoring both biological activities that depend on peptide structure recognition by the GPCRs (such as exocytosis) and those activities dependent on membrane perturbation (such as hemolysis and antibiosis).
Inflammation and apoptosis induced by mastoparan Polybia-MPII on skeletal muscle
2010, Toxicon
Citation Excerpt :
Since the studies of Higashijima et al. (1988), who first demonstrated that mastoparan (MP) activates G-proteins, mainly G0 and G1, the study on the peptide effects has gained impulse, confirming that the great majority of the mastoparan class of peptides involves G-protein signalling. Mastoparan is a remarkable secretagogue exhibiting potent exocytotic activity in a great variety of cell types including mast cells (Hirai et al., 1979), pancreatic islets β-cells (Yokokawa et al., 1989), platelet cells (Ozaki et al., 1990), cromaffin cells (Vitale et al., 1994) and lung alveolar type-2 cells (Joyce-Brady et al., 1991). Other effects include activation of phospholipase A2 (Argiolas and Pisano, 1983) and phospholipase C (Wallace and Carter, 1989).
Mastoparan firstly described as an inducer of mast cell granules exocytosis has been also related to many essential mechanisms of cell function. In skeletal muscle tissue the best characterization of mastoparan effect was induction of myonecrosis. We examined the ability of mastoparan Polybia-MPII from Polybia paulista wasp venom to induce apoptosis and inflammation in mouse tibial anterior muscle. The activation of caspase 3 and 9, the expression of TNF-α, IFN-γ, CD68 and CD163 proteins, specific of resident and migrant macrophages, respectively, were examined (3 h to 21 d). TUNEL-positive nuclei were found both in damaged and normal-looking muscle fibres, whereas the caspases, cytokines and macrophages proteins were only in damaged fibres. The caspase 3 and 9 expression and the immunolabelled areas of TNF-α and IFN-γ were significantly higher compared to control. TUNEL-positive nuclei and TNF-α expression were also present in regenerating fibres. CD68 and CD163 signalize necrotic debris removal, release of chemo-attractants and cytokines which have been considered a pre-requisite for muscle regeneration. High levels of cytokines coincided with the intense muscle proteolysis by mastoparan (3–24 h) and the climax of regeneration (3 d) whereas cytokines decline corresponded to periods of tissue remodeling and intense fibre protein synthesis (7–21 d). We conclude that the mastoparan Polybia-MPII causes myonecrosis and apoptosis, the latter probably involving caspases signalling, corroborated by mitochondrial damage, and cytokines activation.
Characterization of two novel polyfunctional mastoparan peptides from the venom of the social wasp Polybia paulista
2009, Peptides
Hymenoptera venoms are complex mixtures of biochemically and pharmacologically active components such as biogenic amines, peptides and proteins. Polycationic peptides generally constitute the largest group of Hymenoptera venom toxins, and the mastoparans constitute the most abundant and important class of peptides in the venom of social wasps. These toxins are responsible for histamine release from mast cells, serotonin from platelets, and catecholamines and adenylic acids from adrenal chromafin cells. The present work reports the structural and functional characterization of two novel mastoparan peptides identified from the venom of the neotropical social wasp Polybia paulista. The mastoparans Polybia-MP-II and -III were purified, sequenced and synthesized on solid phase using Fmoc chemistry and the synthetic peptides used for structural and functional characterizations. Polybia-MP-II and -III are tetradecapeptides, amidated at their C-termini, and form amphipathic α-helical conformations under membrane-mimetic conditions. Both peptides were polyfunctional, causing pronounced cell lysis of rat mast cells and erythrocytes, in addition to having antimicrobial activity against both Gram-positive and Gram-negative bacteria.
A mastoparan analog without lytic effects and its stimulatory mechanisms in mast cells
2007, Biochemical and Biophysical Research Communications
Mastoparan, a tetradecapeptide isolated from wasp venom, is known to not only induce the secretion of histamine but also cause cell lysis in rat peritoneal mast cells. This lytic effect makes investigations concerning MP-induced signaling mechanisms difficult. Here, we report that a mastoparan derivative peptide, [Lys¹⁰, Leu¹³]mastoparan, also designated “mas 11’’, induces exocytosis with greater activity than mastoparan without the undesired lytic effect. The signaling mechanisms triggered by mas 11 were also investigated, and it was clearly demonstrated that mas 11 induced not only the non-lytic release of β-hexosaminidase but also an increase in the concentration of cytosolic free Ca²⁺ in the cells and these effects were mostly prevented by pertussis toxin, suggesting the involvement of G_i-type G protein in the signaling. Mas 11 is a promising stimulatory molecule with which to investigate the exocytotic mechanisms induced by not only mastoparan but also various amphiphilic peptides in the cells.
Structural and functional characterization of two novel peptide toxins isolated from the venom of the social wasp Polybia paulista
2005, Peptides
Two novel inflammatory peptides were isolated from the venom of the social wasp Polybia paulista. They had their molecular masses determined by ESI-MS and their primary sequences were elucidated by Edman degradation chemistry as:
- •
  Polybia-MPI: I D W K K L L D A A K Q I L-NH₂ (1654.09 Da),
- •
  Polybia-CP: I L G T I L G L L K S L-NH₂ (1239.73 Da).
Both peptides were functionally characterized by using Wistar rat cells. Polybia-MPI is a mast cell lytic peptide, which causes no hemolysis to rat erythrocytes and presents chemotaxis for polymorphonucleated leukocytes (PMNL) and with potent antimicrobial action both against Gram-positive and Gram-negative bacteria. Polybia-CP was characterized as a chemotactic peptide for PMNL cells, presenting antimicrobial action against Gram-positive bacteria, but causing no hemolysis to rat erythrocytes and no mast cell degranulation activity at physiological concentrations.

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Mastoparan, a wasp venom, stimulates insulin release by pancreatic islets through pertussis toxin sensitive GTP-binding protein

Abstract

J. Biol. Chem

J. Biol. Chem

J. Biol. Chem

Eur. J. Pharmacol

J. Biol. Chem

Biochem. Pharmacol

Chem,. Pharm. Bull. (Tokyo)