Journal of Venomous Animals and Toxins Including Tropical Diseases最新文献

{"title":"P-I metalloproteinases and L-amino acid oxidases from <i>Bothrops</i> species inhibit angiogenesis.","authors":"Shreesha K Bhat, Manjunath B Joshi, Sampara Vasishta, Rajesh N Jagadale, Setlur G Biligiri, Monika A Coronado, Raghuvir K Arni, Kapaettu Satyamoorthy","doi":"10.1590/1678-9199-JVATITD-2020-0180","DOIUrl":"10.1590/1678-9199-JVATITD-2020-0180","url":null,"abstract":"<p><strong>Background: </strong>Snake venoms are composed of pharmacologically active proteins that are evolutionarily diverse, stable and specific to targets. Hence, venoms have been explored as a source of bioactive molecules in treating numerous diseases. Recent evidences suggest that snake venom proteins may affect the formation of new blood vessels. Excessive angiogenesis has been implicated in several pathologies including tumours, diabetic retinopathy, arthritis, <i>inter alia</i>. In the present study, we have examined the effects of P-I metalloproteinases isolated from <i>Bothrops moojeni</i> (BmMP-1) and <i>Bothrops atrox</i> (BaMP-1) and L-amino acid oxidases (LAAO) isolated from <i>B. moojeni</i> (BmLAAO) and <i>B. atrox</i> (BaLAAO) on biochemical and functional aspects of angiogenesis.</p><p><strong>Methods: </strong>P-I metalloproteinases and LAAO were purified from venom by molecular size exclusion and ion-exchange chromatography and subsequently confirmed using mass spectrometry. The P-I metalloproteinases were characterized by azocaseinolytic, fibrinogenolytic and gelatinase activity and LAAO activity was assessed by enzyme activity on L-amino acids. Influence of these proteins on apoptosis and cell cycle in endothelial cells was analysed by flow cytometry. The angiogenic activity was determined by <i>in vitro</i> 3D spheroid assay, Matrigel tube forming assay, and <i>in vivo</i> agarose plug transformation in mice.</p><p><strong>Results: </strong>P-I metalloproteinases exhibited azocaseinolytic activity, cleaved α and partially β chain of fibrinogen, and displayed catalytic activity on gelatin. LAAO showed differential activity on L-amino acids. Flow cytometry analysis indicated that both P-I metalloproteinases and LAAO arrested the cells in G0/G1 phase and further induced both necrosis and apoptosis in endothelial cells. <i>In vitro,</i> P-I metalloproteinases and LAAO exhibited significant anti-angiogenic properties in 3D spheroid and Matrigel models by reducing sprout outgrowth and tube formation. Using agarose plug transplants in mice harbouring P-I metalloproteinases and LAAO we demonstrated a marked disruption of vasculature at the periphery.</p><p><strong>Conclusion: </strong>Our research suggests that P-I metalloproteinases and LAAO exhibit anti-angiogenic properties <i>in vitro</i> and <i>in vivo</i>.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39375991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic characterization of <i>Naja mandalayensis</i> venom.","authors":"Emídio Beraldo,&nbsp;Guilherme Rabelo Coelho,&nbsp;Juliana Mozer Sciani,&nbsp;Daniel Carvalho Pimenta","doi":"10.1590/1678-9199-JVATITD-2020-0125","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0125","url":null,"abstract":"<p><strong>Background: </strong><i>Naja mandalayensis</i> is a spitting cobra from Myanmar. To the best of our knowledge, no studies on this venom composition have been conducted so far. On the other hand, few envenomation descriptions state that it elicits mainly local inflammation in the victims' eyes, the preferred target of this spiting cobra. Symptoms would typically include burning and painful sensation, conjunctivitis, edema and temporary loss of vision.</p><p><strong>Methods: </strong>We have performed a liquid-chromatography (C18-RP-HPLC) mass spectrometry (ESI-IT-TOF/MS) based approach in order to biochemically characterize <i>N. mandalayensis</i> venom.</p><p><strong>Results: </strong>A wide variety of three-finger toxins (cardiotoxins) and metallopeptidases were detected. Less abundant, but still representative, were cysteine-rich secretory proteins, L-amino-acid oxidases, phospholipases A₂, venom 5'-nucleotidase and a serine peptidase inhibitor. Other proteins were present, but were detected in a relatively small concentration.</p><p><strong>Conclusion: </strong>The present study set the basis for a better comprehension of the envenomation from a molecular perspective and, by increasing the interest and information available for this species, allows future venom comparisons among cobras and their diverse venom proteins.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39324554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and kidney involvement in human viral diseases caused by SARS-CoV-2, HIV, HCV and HBV.","authors":"Gustavo Ferreira da Mata,&nbsp;Danilo Euclides Fernandes,&nbsp;Eduardo de Paiva Luciano,&nbsp;Gabriel Teixeira Montezuma Sales,&nbsp;Michelle Tiveron Passos Riguetti,&nbsp;Gianna Mastroianni Kirsztajn","doi":"10.1590/1678-9199-JVATITD-2020-0154","DOIUrl":"10.1590/1678-9199-JVATITD-2020-0154","url":null,"abstract":"<p><p>Inflammation is closely related to renal diseases. This is particularly true for renal diseases caused by infections as in viral diseases. In this review, we highlight the inflammatory mechanisms that underlie kidney dysfunction in SARS-CoV-2, human immunodeficiency (HIV), hepatitis C (HCV), and hepatitis B (HBV) infections. The pathophysiology of renal involvement in COVID-19 is complex, but kidney damage is frequent, and the prognosis is worse when it happens. Virus-like particles were demonstrated mostly in renal tubular epithelial cells and podocytes, which suggest that SARS-CoV-2 directly affects the kidneys. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor, which is found in endothelial cells, to infect the human host cells. Critical patients with SARS-CoV-2-associated acute kidney injury (AKI) show an increase in inflammatory cytokines (IL-1β, IL-8, IFN-γ, TNF-α), known as cytokine storm that favors renal dysfunction by causing intrarenal inflammation, increased vascular permeability, volume depletion, thromboembolic events in microvasculature and persistent local inflammation. Besides AKI, SARS-CoV-2 can also cause glomerular disease, as other viral infections such as in HIV, HBV and HCV. HIV-infected patients present chronic inflammation that can lead to a number of renal diseases. Proinflammatory cytokines and TNF-induced apoptosis are some of the underlying mechanisms that may explain the virus-induced renal diseases that are here reviewed.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39302551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brown spider venom toxins: what are the functions of astacins, serine proteases, hyaluronidases, allergens, TCTP, serpins and knottins?","authors":"Luiza Helena Gremski,&nbsp;Fernando Hitomi Matsubara,&nbsp;Hanna Câmara da Justa,&nbsp;Zelinda Schemczssen-Graeff,&nbsp;Antonielle Beatriz Baldissera,&nbsp;Pedro Henrique de Caires Schluga,&nbsp;Isabel de Oliveira Leite,&nbsp;Marianna Boia-Ferreira,&nbsp;Ana Carolina Martins Wille,&nbsp;Andrea Senff-Ribeiro,&nbsp;Silvio Sanches Veiga","doi":"10.1590/1678-9199-JVATITD-2020-0188","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0188","url":null,"abstract":"<p><p>Accidents caused by the bites of brown spiders (<i>Loxosceles</i>) generate a clinical condition that often includes a threatening necrotic skin lesion near the bite site along with a remarkable inflammatory response. Systemic disorders such as hemolysis, thrombocytopenia, and acute renal failure may occur, but are much less frequent than the local damage. It is already known that phospholipases D, highly expressed toxins in <i>Loxosceles</i> venom, can induce most of these injuries. However, this spider venom has a great range of toxins that probably act synergistically to enhance toxicity. The other protein classes remain poorly explored due to the difficulty in obtaining sufficient amounts of them for a thorough investigation. They include astacins (metalloproteases), serine proteases, knottins, translationally controlled tumor proteins (TCTP), hyaluronidases, allergens and serpins. It has already been shown that some of them, according to their characteristics, may participate to some extent in the development of loxoscelism. In addition, all of these toxins present potential application in several areas. The present review article summarizes information regarding some functional aspects of the protein classes listed above, discusses the directions that could be taken to materialize a comprehensive investigation on each of these toxins as well as highlights the importance of exploring the full venom repertoire.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39298841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MS/MS analysis of four scorpion venoms from Colombia: a descriptive approach.","authors":"Sebastian Estrada-Gómez,&nbsp;Leidy Johana Vargas-Muñoz,&nbsp;Monica Maria Saldarriaga-Córdoba,&nbsp;Arie van der Meijden","doi":"10.1590/1678-9199-JVATITD-2020-0173","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0173","url":null,"abstract":"<p><strong>Background: </strong>Scorpions are widely known for the neurotoxic effects of their venoms, which contain peptides affecting ionic channels. Although Colombia is recognized for its scorpion diversity, only a few studies are available describing the venom content.</p><p><strong>Methods: </strong>In this descriptive study, we analyzed the MS/MS sequence, electrophoretic and chromatographic profile linked to a bioinformatics analysis of the scorpions <i>Chactas reticulatus</i> (Chactidae), <i>Opisthacanthus elatus</i> (Hormuridae), <i>Centruroides edwardsii</i> (Buthidae) and <i>Tityus asthenes</i> (Buthidae) from Colombia.</p><p><strong>Results: </strong>Each scorpion showed a specific electrophoretic and chromatographic profile. The electrophoretic profiles indicate the presence of high molecular mass compounds in all venoms, with a predominance of low molecular mass compounds in the Buthidae species. Chromatographic profiles showed a similar pattern as the electrophoretic profiles. From the MS/MS analysis of the chromatographic collected fractions, we obtained internal peptide sequences corresponding to proteins reported in scorpions from the respective family of the analyzed samples. Some of these proteins correspond to neurotoxins affecting ionic channels, antimicrobial peptides and metalloproteinase-like fragments. In the venom of <i>Tityus asthenes,</i> the MSⁿ analysis allowed the detection of two toxins affecting sodium channels covering 50% and 84% of the sequence respectively, showing 100% sequence similarity. Two sequences from <i>Tityus asthenes</i> showed sequence similarity with a phospholipase from <i>Opisthacanthus cayaporum</i> indicating the presence of this type of toxin in this species for the first time. One sequence matching a hypothetical secreted protein from <i>Hottentotta judaicus</i> was found in three of the studied venoms. We found that this protein is common in the Buthidae family whereas it has been reported in other families - such as Scorpionidae - and may be part of the evolutionary puzzle of venoms in these arachnids.</p><p><strong>Conclusion: </strong>Buthidae venoms from Colombia can be considered an important source of peptides similar to toxins affecting ionic channels. An interesting predicted antimicrobial peptide was detected in three of the analyzed venoms.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39207487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of climate variables on the incidence of scorpion stings in Iran for five years.","authors":"Ahmad Ghorbani,&nbsp;Behzad Mansouri,&nbsp;Masoumeh Baradaran","doi":"10.1590/1678-9199-JVATITD-2020-0110","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0110","url":null,"abstract":"<p><strong>Background: </strong>Although scorpionism is recorded worldwide, some regions such as Iran present a higher incidence. Due to the great prevalence of scorpion stings in Khuzestan province, southwestern Iran, the present study examined the relationship between different climate parameters and the scorpion sting rate in this area from April 2010 to March 2015.</p><p><strong>Methods: </strong>In this cross-sectional descriptive-analytical study, we considered all scorpion sting cases recorded in the Department of Infectious Diseases, Ahvaz Jundishapur University of Medical Sciences. Data were analyzed using statistics, frequency distribution and Pearson's correlation coefficient.</p><p><strong>Results: </strong>A total of 104,197 cases of scorpion stings was recorded from 2010 to 2015. The cumulative incidence of scorpion sting was 2.23%. The spatial distribution of scorpion stings showed that most cases occurred in the Dehdez district (4,504 scorpion stings/100,000 inhabitants) and the Masjed Soleyman county (4,069 scorpion stings/100,000 inhabitants). A significant association was found between climate factors (temperature, evaporation rate, sunshine duration, humidity, and precipitation) and the scorpion sting rate. An increase in rainfall and humidity coincided with a reduction in scorpion stings whereas an increase in temperature, evaporation, and sunshine duration was accompanied by a growth of scorpion stings. No significant correlation was found between wind velocity/direction and the incidence rate of stings. Moreover, the seasonal peak incidence of scorpion stings was recorded in summer (an average of 8,838 cases) and the lowest incidence was recorded during winter (an average of 1,286 cases). The annual trend of scorpion sting cases decreased during the period from 2010 to 2015.</p><p><strong>Conclusion: </strong>Climate variables can be a good index for predicting the incidence of scorpion stings in endemic regions. Since they occur mostly in the hot season, designing preventive measures in the counties and districts with a high incidence of scorpion stings such as Dehdez and Masjed Soleyman can minimize mortality and other burdens.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39185373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of venoms on neutrophil respiratory burst: a major inflammatory function.","authors":"Jamel El-Benna,&nbsp;Margarita Hurtado-Nedelec,&nbsp;Marie-Anne Gougerot-Pocidalo,&nbsp;Pham My-Chan Dang","doi":"10.1590/1678-9199-JVATITD-2020-0179","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0179","url":null,"abstract":"<p><p>Neutrophils play a pivotal role in innate immunity and in the inflammatory response. Neutrophils are very motile cells that are rapidly recruited to the inflammatory site as the body first line of defense. Their bactericidal activity is due to the release into the phagocytic vacuole, called phagosome, of several toxic molecules directed against microbes. Neutrophil stimulation induces release of this arsenal into the phagosome and induces the assembly at the membrane of subunits of the NAPDH oxidase, the enzyme responsible for the production of superoxide anion that gives rise to other reactive oxygen species (ROS), a process called respiratory burst. Altogether, they are responsible for the bactericidal activity of the neutrophils. Excessive activation of neutrophils can lead to extensive release of these toxic agents, inducing tissue injury and the inflammatory reaction. Envenomation, caused by different animal species (bees, wasps, scorpions, snakes etc.), is well known to induce a local and acute inflammatory reaction, characterized by recruitment and activation of leukocytes and the release of several inflammatory mediators, including prostaglandins and cytokines. Venoms contain several molecules such as enzymes (phospholipase A2, L-amino acid oxidase and proteases, among others) and peptides (disintegrins, mastoporan, parabutoporin etc.). These molecules are able to stimulate or inhibit ROS production by neutrophils. The present review article gives a general overview of the main neutrophil functions focusing on ROS production and summarizes how venoms and venom molecules can affect this function.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39174071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroactive venom compounds obtained from <i>Phlogiellus bundokalbo</i> as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities <i>in vitro</i>.","authors":"Simon Miguel M Lopez,&nbsp;Jeremey S Aguilar,&nbsp;Jerene Bashia B Fernandez,&nbsp;Angelic Gayle J Lao,&nbsp;Mitzi Rain R Estrella,&nbsp;Mark Kevin P Devanadera,&nbsp;Cydee Marie V Ramones,&nbsp;Aaron Joseph L Villaraza,&nbsp;Leonardo A Guevarra,&nbsp;Myla R Santiago-Bautista,&nbsp;Librado A Santiago","doi":"10.1590/1678-9199-JVATITD-2021-0009","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2021-0009","url":null,"abstract":"<p><strong>Background: </strong>Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of <i>Phlogiellus bundokalbo</i> venom against neurodegenerative diseases.</p><p><strong>Methods: </strong>Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from <i>Terebrio molitor</i> larvae <i>in vivo</i> and fractions were screened for their inhibitory activities against AChE and BACE <i>in vitro</i>.</p><p><strong>Results: </strong>The whole venom from <i>P. bundokalbo</i> demonstrated neuroactivity by inducing excitatory movements from <i>T. molitor</i> for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control.</p><p><strong>Conclusion: </strong>The venom of <i>P. bundokalbo</i> contains compounds that demonstrate neuroactivity and anti-AChE activities <i>in vitro</i>, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39174072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel proline-rich M-superfamily conotoxin that can simultaneously affect sodium, potassium and calcium currents.","authors":"Manyi Yang,&nbsp;Yubin Li,&nbsp;Longfei Liu,&nbsp;Maojun Zhou","doi":"10.1590/1678-9199-JVATITD-2020-0164","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0164","url":null,"abstract":"<p><strong>Background: </strong>Conotoxins have become a research hotspot in the neuropharmacology field for their high activity and specificity in targeting ion channels and neurotransmitter receptors. There have been reports of a conotoxin acting on two ion channels, but rare reports of a conotoxin acting on three ion channels.</p><p><strong>Methods: </strong>Vr3a, a proline-rich M-superfamily conotoxin from a worm-hunting <i>Conus varius</i>, was obtained by solid-phase synthesis and identified by mass spectrometry. The effects of synthesized Vr3a on sodium, potassium and calcium currents were tested on rat DRG cells by patch clamp experiments. The further effects of Vr3a on human Ca_v1.2 and Ca_v2.2 currents were tested on HEK293 cells.</p><p><strong>Results: </strong>About 10 μM Vr3a has no effects on the peak sodium currents, but can induce a ~10 mV shift in a polarizing direction in the current-voltage relationship. In addition, 10 μM Vr3a can increase 19.61 ± 5.12% of the peak potassium currents and do not induce a shift in the current-voltage relationship. An amount of 10 μM Vr3a can inhibit 31.26% ± 4.53% of the peak calcium currents and do not induce a shift in the current-voltage relationship. The IC₅₀ value of Vr3a on calcium channel currents in rat DRG neurons is 19.28 ± 4.32 μM. Moreover, 10 μM Vr3a can inhibit 15.32% ± 5.41% of the human Ca_v1.2 currents and 12.86% ± 4.93% of the human Ca_v2.2 currents.</p><p><strong>Conclusions: </strong>Vr3a can simultaneously affect sodium, potassium and calcium currents. This novel triple-target conotoxin Vr3a expands understanding of conotoxin functions.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39162463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel neuroprotective peptides in the venom of the solitary scoliid wasp <i>Scolia decorata ventralis</i>.","authors":"Carlos Alberto-Silva,&nbsp;Fernanda Calheta Vieira Portaro,&nbsp;Roberto Tadashi Kodama,&nbsp;Halyne Queiroz Pantaleão,&nbsp;Marisa Rangel,&nbsp;Ken-Ichi Nihei,&nbsp;Katsuhiro Konno","doi":"10.1590/1678-9199-JVATITD-2020-0171","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0171","url":null,"abstract":"<p><strong>Background: </strong>Solitary 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, <i>Scolia decorata ventralis</i>, was investigated through a comprehensive analysis using LC-MS. Two peptides were synthesized, and their neuroprotective properties were evaluated.</p><p><strong>Methods: </strong>A 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.</p><p><strong>Results: </strong>Online 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.</p><p><strong>Conclusion: </strong>Comprehensive LC-MS and MS/MS analyses from the <i>Scolia decorata ventralis</i> 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.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39045244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}