Novel neuroprotective peptides in the venom of the solitary scoliid wasp Scolia decorata ventralis

Carlos Alberto-Silva,Halyne Queiroz Pantaleão,Marisa Rangel,Fernanda Calheta Vieira Portaro,Katsuhiro Konno,Roberto Tadashi Kodama,Ken-Ichi Nihei

doi:10.1590/1678-9199-jvatitd-2020-0171

Abstract

BackgroundSolitary wasp venoms may be a rich source of neuroactive substances, since their venoms are used for paralyzing preys. We have been exploring bioactive constituents of solitary wasp venoms and, in this study, the component profile of the venom from a solitary scoliid wasp, Scolia decorata ventralis, was investigated through a comprehensive analysis using LC-MS. Two peptides were synthesized, and their neuroprotective properties were evaluated.MethodsA reverse-phase HPLC connected to ESI-MS was used for LC-MS analyses. Online mass fingerprinting was performed from TIC, and data-dependent tandem mass spectrometry gave the MS/MS spectra. The sequences of two major peptide components were determined by MALDI-TOF/TOF MS analysis, confirmed by solid phase synthesis. Using the synthetic peptides, biological activities were assessed. Cell integrity tests and neuroprotection analyzes using H2O2 as an oxidative stress inducer were performed for both peptides.ResultsOnline mass fingerprinting revealed that the venom contains 123 components, and the MS/MS analysis resulted in 33 full sequences of peptide components. The two main peptides, α-scoliidine (DYVTVKGFSPLR) and β-scoliidine (DYVTVKGFSPLRKA), present homology with the bradykinin C-terminal. Despite this, both peptides did not behave as substrates or inhibitors of ACE, indicating that they do not interact with this metallopeptidase. In further studies, β-scoliidine, but not α -scoliidine, showed protective effects against oxidative stress-induced neurotoxicity in PC12 cells through integrity and metabolism cell assays. Interestingly, β-scoliidine has the extension of the KA dipeptide at the C-terminal in comparison with α-scoliidine.ConclusionComprehensive LC-MS and MS/MS analyses from the Scolia decorata ventralis venom displayed the component profile of this venom. β-scoliidine showed an effective cytoprotective effect, probably due to the observed increase in the number of cells. This is the first report of solitary wasp venom peptides showing neuroprotective activity.

Highlights

Solitary wasp venoms may be a rich source of neuroactive substances, since their venoms are used for paralyzing preys
The crude venom extract was first subjected to LC-ESI-matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MS) in order to verify the component profile: number of components and its molecular mass determination
Online mass fingerprint was prepared from total ion current (TIC) by “virtual fractionation”, collecting MS spectra from certain range of retention time, and the molecular mass was analyzed in each fraction

Summary

Introduction

Solitary wasp venoms may be a rich source of neuroactive substances, since their venoms are used for paralyzing preys. Spider and scorpion venoms have a variety of neuroactive peptides acting on ion channels and receptors They have been used for studying neuronal functions and some of them may be useful for medical and agricultural application [2,3]. It is the case for Hymenopteran insect venoms from social bees and wasps such as honeybees and hornets. We are interested in solitary wasps and have researched their venom components over the past few decades Solitary wasps use their venoms to capture and paralyze their prey, insects and spiders, and feed their larvae with paralyzed prey [5]. Our studies of solitary wasp venom components revealed that the venoms contain neuroactive peptides and a variety of bioactive peptides [11]

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