Toxins最新文献

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Conotoxins: Classification, Prediction, and Future Directions in Bioinformatics. Conotoxins:分类,预测和未来的方向在生物信息学。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-09 DOI: 10.3390/toxins17020078
Rui Li, Junwen Yu, Dongxin Ye, Shanghua Liu, Hongqi Zhang, Hao Lin, Juan Feng, Kejun Deng
{"title":"Conotoxins: Classification, Prediction, and Future Directions in Bioinformatics.","authors":"Rui Li, Junwen Yu, Dongxin Ye, Shanghua Liu, Hongqi Zhang, Hao Lin, Juan Feng, Kejun Deng","doi":"10.3390/toxins17020078","DOIUrl":"10.3390/toxins17020078","url":null,"abstract":"<p><p>Conotoxins, a diverse family of disulfide-rich peptides derived from the venom of <i>Conus</i> species, have gained prominence in biomedical research due to their highly specific interactions with ion channels, receptors, and neurotransmitter systems. Their pharmacological properties make them valuable molecular tools and promising candidates for therapeutic development. However, traditional conotoxin classification and functional characterization remain labor-intensive, necessitating the increasing adoption of computational approaches. In particular, machine learning (ML) techniques have facilitated advancements in sequence-based classification, functional prediction, and de novo peptide design. This review explores recent progress in applying ML and deep learning (DL) to conotoxin research, comparing key databases, feature extraction techniques, and classification models. Additionally, we discuss future research directions, emphasizing the integration of multimodal data and the refinement of predictive frameworks to enhance therapeutic discovery.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493406","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}
引用次数: 0
Fifty Years of Aflatoxin Research in Qidong, China: A Celebration of Team Science to Improve Public Health. 中国启东黄曲霉毒素研究五十年:庆祝团队科学改善公众健康。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-09 DOI: 10.3390/toxins17020079
Jian-Guo Chen, Yuan-Rong Zhu, Geng-Sun Qian, Jin-Bing Wang, Jian-Hua Lu, Thomas W Kensler, Lisa P Jacobson, Alvaro Muñoz, John D Groopman
{"title":"Fifty Years of Aflatoxin Research in Qidong, China: A Celebration of Team Science to Improve Public Health.","authors":"Jian-Guo Chen, Yuan-Rong Zhu, Geng-Sun Qian, Jin-Bing Wang, Jian-Hua Lu, Thomas W Kensler, Lisa P Jacobson, Alvaro Muñoz, John D Groopman","doi":"10.3390/toxins17020079","DOIUrl":"10.3390/toxins17020079","url":null,"abstract":"<p><p>The Qidong Liver Cancer Institute (QDLCI) and the Qidong Cancer Registry were established in 1972 with input from doctors, other medical practitioners, and non-medical investigators arriving from urban centers such as Shanghai and Nanjing. Medical teams were established to quantify the extent of primary liver cancer in Qidong, a corn-growing peninsula on the north side of the Yangtze River. High rates of liver cancer were documented and linked to several etiologic agents, including aflatoxins. Local corn, the primary dietary staple, was found to be consistently contaminated with high levels of aflatoxins, and bioassays using this corn established its carcinogenicity in ducks and rats. Observational studies noted a positive association between levels of aflatoxin in corn and incidence of liver cancer across townships. Biomarker studies measuring aflatoxin B<sub>1</sub> and its metabolite aflatoxin M<sub>1</sub> in biofluids reflected the exposures. Approaches to decontamination of corn from aflatoxins were also studied. In 1993, investigators from Johns Hopkins University were invited to visit the QDLCI to discuss chemoprevention studies in some townships. A series of placebo-controlled clinical trials were conducted using oltipraz (a repurposed drug), chlorophyllin (an over-the-counter drug), and beverages prepared from 3-day-old broccoli sprouts (rich in the precursor phytochemical for sulforaphane). Modulation of biomarkers of aflatoxin DNA and albumin adducts established proof of principle for the efficacy of these agents in enhancing aflatoxin detoxication. Serendipitously, by 2012, aflatoxin exposures quantified using biomarker measurements documented a many hundred-fold reduction. In turn, the Cancer Registry documents that the age-standardized incidence rate of liver cancer is now 75% lower than that seen in the 1970s. This reduction is seen in Qidongese who have never received the hepatitis B vaccination. Aflatoxin mitigation driven by economic changes switched the dietary staple of contaminated corn to rice coupled with subsequent dietary diversity leading to lower aflatoxin exposures. This 50-year effort to understand the etiology of liver cancer in Qidong provides the strongest evidence for aflatoxin mitigation as a public health strategy for reducing liver cancer burden in exposed, high-risk populations. Also highlighted are the challenges and successes of international team science to solve pressing public health issues.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493612","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}
引用次数: 0
An Update of Tetrodotoxins Toxicity and Risk Assessment Associated to Contaminated Seafood Consumption in Europe: A Systematic Review. 欧洲食用受污染海产品有关河豚毒素毒性和风险评估的最新进展:一项系统综述。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-08 DOI: 10.3390/toxins17020076
Carlo Varini, Maura Manganelli, Simona Scardala, Pietro Antonelli, Carmen Losasso, Emanuela Testai
{"title":"An Update of Tetrodotoxins Toxicity and Risk Assessment Associated to Contaminated Seafood Consumption in Europe: A Systematic Review.","authors":"Carlo Varini, Maura Manganelli, Simona Scardala, Pietro Antonelli, Carmen Losasso, Emanuela Testai","doi":"10.3390/toxins17020076","DOIUrl":"10.3390/toxins17020076","url":null,"abstract":"<p><p>Following the occurrence of Tetrodotoxins (TTXs) in Europe-a group of neurotoxins identified in Asia, where fatalities occurred after the ingestion of contaminated pufferfish-the EFSA proposed a limit of 44 µg of TTX/kg of shellfish meat in mollusks in 2017, to protect heavy consumers. The limit was based on an acute reference dose (ARfD) derived from the few available data on TTX toxicity. TTX is expected to increase with sea-surface warming; indeed, it has been found in spring/summer in mollusks in Europe, with concentrations often exceeding this limit. Due to the numerous uncertainties of the EFSA's ARfD, we conducted a systematic review to provide an update on TTX toxicity. Out of 12,741 articles retrieved from PubMed, Science Direct, and Scopus since 2017, only 17 were eligible for data extraction. Our results show that they are not sufficient to modify the EFSA's conclusions. Furthermore, our analysis of occurrence data in European seafood, to assess the current risk of exposure to TTX, reveals several gaps, such as different LODs/LOQs and seasonal monitoring not allowing comparisons between areas and too few analyzed sites. However, the presence of positive samples exceeding the EFSA limit indicates a potential risk even for general consumers, highlighting the urgency to address these knowledge gaps.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493355","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}
引用次数: 0
Investigating the Correlations Between Weather Factors and Mycotoxin Contamination in Corn: Evidence from Long-Term Data. 研究天气因素与玉米霉菌毒素污染的相关性:来自长期数据的证据。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-08 DOI: 10.3390/toxins17020077
Alexander Platzer, Younos Cherkaoui, Barbara Novak, Gerd Schatzmayr
{"title":"Investigating the Correlations Between Weather Factors and Mycotoxin Contamination in Corn: Evidence from Long-Term Data.","authors":"Alexander Platzer, Younos Cherkaoui, Barbara Novak, Gerd Schatzmayr","doi":"10.3390/toxins17020077","DOIUrl":"10.3390/toxins17020077","url":null,"abstract":"<p><p>Mycotoxins are secondary metabolites produced by certain fungi, posing significant health risks to humans and animals through contaminated food and feed. These fungi, and consequently the mycotoxins which they produce, are strongly influenced by weather, and this shifts over time due to climate change, leading to more frequent and severe events, such as heat waves, storms, and heavy rainfall. This study investigates how long-term weather trends and climatic factors impacted mycotoxin levels in corn samples over a 17-year period (2006-2022) across 12 countries, with a focus on 136 specific weather features. Among all potential relationships, we found <i>Aspergillus</i> toxins and fumonisins to be positively correlated with temperature, while deoxynivalenol and zearalenone are negatively correlated. Additionally, the dew point, particularly its 90th percentile value, is positively correlated with <i>Aspergillus</i> mycotoxins. We also identified significant patterns associated with wind direction. Collectively, these findings offer a comprehensive overview of mycotoxin-weather correlations, which may also be projected into future scenarios.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493629","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}
引用次数: 0
Metabolomic Profiling of Human Urine Related to Mycotoxin Exposure. 与霉菌毒素暴露相关的人类尿液代谢组学分析。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-08 DOI: 10.3390/toxins17020075
Nuria Dasí-Navarro, Sonia Lombardi, Pilar Vila-Donat, Sabrina Llop, Jesus Vioque, Raquel Soler-Blasco, Ana Esplugues, Lara Manyes, Manuel Lozano
{"title":"Metabolomic Profiling of Human Urine Related to Mycotoxin Exposure.","authors":"Nuria Dasí-Navarro, Sonia Lombardi, Pilar Vila-Donat, Sabrina Llop, Jesus Vioque, Raquel Soler-Blasco, Ana Esplugues, Lara Manyes, Manuel Lozano","doi":"10.3390/toxins17020075","DOIUrl":"10.3390/toxins17020075","url":null,"abstract":"<p><p>Human exposure to mycotoxins is a global concern since several mycotoxins, such as enniatins and aflatoxins, have shown carcinogenic and neurotoxic effects, and the toxicologic mechanisms of most of them still need to be clarified. This study aims to investigate the metabolic pathways affected by mycotoxin exposure by evaluating metabolite alterations in urine. The participants were 540 women from the Spanish Childhood and Environment Project (INMA). For metabolite identification, a dilute and shoot extraction, followed by HPLC-Q-TOF-MS identification analysis, was performed. Data were processed using Agilent Mass Hunter Workstation with the METLIN database, Agilent Mass Profiler Professional 10.0, and Metaboanalyst 6.0. Over 2000 metabolites were obtained in each sample after feature extraction, and the most significant metabolites (<i>p</i>-value ≤ 0.05, fold change ≥ 2.0) were considered for pathway analysis. Enrichment analysis and topology showed that the most significantly affected pathway was the biosynthesis of unsaturated fatty acids (adjusted <i>p</i>-value = 0.007), with four metabolomic hits associated: linoleic acid, octadecanoic acid/stearic acid, an arachidonic acid metabolite, and (9Z)-octadecenoic acid/oleic acid. Other related pathways (unadjusted <i>p</i>-value ≤ 0.1) included fatty acid biosynthesis, glycerophospholipid metabolism, and ether lipid metabolism. The present study highlights the importance of metabolomics in increasing knowledge of the toxicity mechanisms and health effects of mycotoxins, especially emerging ones.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493630","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}
引用次数: 0
Targeting Enterotoxins: Advancing Vaccine Development for Enterotoxigenic Escherichia coli ETEC. 靶向肠毒素:推进产肠毒素大肠杆菌ETEC疫苗的开发。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-06 DOI: 10.3390/toxins17020071
Josune Salvador-Erro, Yadira Pastor, Carlos Gamazo
{"title":"Targeting Enterotoxins: Advancing Vaccine Development for Enterotoxigenic <i>Escherichia coli</i> ETEC.","authors":"Josune Salvador-Erro, Yadira Pastor, Carlos Gamazo","doi":"10.3390/toxins17020071","DOIUrl":"10.3390/toxins17020071","url":null,"abstract":"<p><p>Enterotoxigenic <i>Escherichia coli</i> (ETEC) is a major cause of diarrheal disease worldwide, particularly in children in low- and middle-income countries. Its ability to rapidly colonize the intestinal tract through diverse colonization factors and toxins underpins its significant public health impact. Despite extensive research and several vaccine candidates reaching clinical trials, no licensed vaccine exists for ETEC. This review explores the temporal and spatial coordination of ETEC virulence factors, focusing on the interplay between adherence mechanisms and toxin production as critical targets for therapeutic intervention. Advancements in molecular biology and host-pathogen interaction studies have uncovered species-specific variations and cross-reactivity between human and animal strains. In particular, the heat-labile (LT) and heat-stable (ST) toxins have provided crucial insights into molecular mechanisms and intestinal disruption. Additional exotoxins, such as EAST-1 and hemolysins, further highlight the multifactorial nature of ETEC pathogenicity. Innovative vaccine strategies, including multiepitope fusion antigens (MEFAs), mRNA-based approaches, and glycoconjugates, aim to enhance broad-spectrum immunity. Novel delivery methods, like intradermal immunization, show promise in eliciting robust immune responses. Successful vaccination against ETEC will offer an effective and affordable solution with the potential to greatly reduce mortality and prevent stunting, representing a highly impactful and cost-efficient solution to a critical global health challenge.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493414","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}
引用次数: 0
Pore-Forming Protein LIN-24 Enhances Starvation Resilience in Caenorhabditis elegans by Modulating Lipid Metabolism and Mitochondrial Dynamics. 孔形成蛋白 LIN-24 通过调节脂质代谢和线粒体动力学增强秀丽隐杆线虫的饥饿恢复能力
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-06 DOI: 10.3390/toxins17020072
Xinqiang Lan, Mengqi Yang, Jiali Wang, Chunping Huang, Andong Wu, Leilei Cui, Yingqi Guo, Lin Zeng, Xiaolong Guo, Yun Zhang, Yang Xiang, Qiquan Wang
{"title":"Pore-Forming Protein LIN-24 Enhances Starvation Resilience in <i>Caenorhabditis elegans</i> by Modulating Lipid Metabolism and Mitochondrial Dynamics.","authors":"Xinqiang Lan, Mengqi Yang, Jiali Wang, Chunping Huang, Andong Wu, Leilei Cui, Yingqi Guo, Lin Zeng, Xiaolong Guo, Yun Zhang, Yang Xiang, Qiquan Wang","doi":"10.3390/toxins17020072","DOIUrl":"10.3390/toxins17020072","url":null,"abstract":"<p><p>The ability to survive starvation is a critical evolutionary adaptation, yet the molecular mechanisms underlying this capability remain incompletely understood. Pore-forming proteins (PFPs) are typically associated with immune defense, where they disturb the membranes of target cells. However, the role of PFPs in non-immune functions, particularly in metabolic and structural adaptations to starvation, is less explored. Here, we investigate the aerolysin-like PFP LIN-24 in <i>Caenorhabditis elegans</i> and uncover its novel function in enhancing starvation resistance. We found that LIN-24 expression is upregulated during starvation, leading to increased expression of the lipase-encoding gene <i>lipl-3</i>. This upregulation accelerates the mobilization and degradation of lipid stores, thereby sustaining energy levels. Additionally, LIN-24 overexpression significantly preserves muscle integrity, as evidenced by the maintenance of muscle structure compared to wild-type worms. Furthermore, we demonstrate that LIN-24 induces the formation of donut-shaped mitochondria, a structural change likely aimed at reducing ATP production to conserve energy during prolonged nutrient deprivation. This mitochondrial remodeling depends on genes involved in mitochondrial dynamics, including <i>mff-1</i>, <i>mff-2</i>, <i>drp-1</i>, and <i>clk-1</i>. Collectively, these findings expand our understanding of PFPs, demonstrating their multifaceted role in stress resistance beyond immune defense. LIN-24's involvement in regulating metabolism, preserving muscle structure, and remodeling mitochondria highlights its crucial role in the adaptive response to starvation, offering novel insights into the evolution of stress resistance mechanisms and potential therapeutic targets for conditions related to muscle preservation and metabolic regulation.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493648","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}
引用次数: 0
Detection of Ochratoxin A in Tissues of Wild Boars (Sus scrofa) from Southern Italy. 意大利南部野猪组织中赭曲霉毒素A的检测。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-06 DOI: 10.3390/toxins17020074
Sara Damiano, Consiglia Longobardi, Lucia De Marchi, Nadia Piscopo, Valentina Meucci, Alessio Lenzi, Roberto Ciarcia
{"title":"Detection of Ochratoxin A in Tissues of Wild Boars (<i>Sus scrofa</i>) from Southern Italy.","authors":"Sara Damiano, Consiglia Longobardi, Lucia De Marchi, Nadia Piscopo, Valentina Meucci, Alessio Lenzi, Roberto Ciarcia","doi":"10.3390/toxins17020074","DOIUrl":"10.3390/toxins17020074","url":null,"abstract":"<p><p>Ochratoxin A (OTA) is a secondary metabolite produced by fungi of the genera <i>Aspergillus</i> and <i>Penicillium</i>, known to contaminate various food substrates. Its toxic effects include direct nephrotoxicity, as well as observed teratogenic, immunogenic, and carcinogenic effects. Climate change may contribute to increased humidity and temperature, favouring fungal growth and, consequently, OTA spreading. Recent increases in wild boar populations, along with their omnivorous nature and their varied diet, define them as environmental bioindicators for contaminants like mycotoxins. This study aimed to assess the concentrations of OTA in kidney, liver, and muscle tissue samples from 74 wild boars that were hunted in different areas of Avellino, Campania region, between 2021 and 2022. Tissue samples underwent extraction, purification, and analysis using high-performance liquid chromatography (HPLC) coupled with a fluorescence detector. Results revealed OTA presence in 35.1% of tested wild boars. The highest OTA concentration was observed in the kidney and liver, with less in the muscle, indicating the presence of this mycotoxin in the wild boars and their surrounding environment. Consequently, there is a need to formulate rules for edible wildlife products. These findings emphasize the significant risk of OTA contamination in wild boar tissues, suggesting their potential as reliable environmental markers for mycotoxin prevalence and as a toxicological concern for human health.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493438","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}
引用次数: 0
α-Latrotoxin Actions in the Absence of Extracellular Ca2+ Require Release of Stored Ca2. 缺乏细胞外Ca2+时α- latotoxin的作用需要释放储存的Ca2。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-06 DOI: 10.3390/toxins17020073
Jennifer K Blackburn, Quazi Sufia Islam, Ouafa Benlaouer, Svetlana A Tonevitskaya, Evelina Petitto, Yuri A Ushkaryov
{"title":"α-Latrotoxin Actions in the Absence of Extracellular Ca<sup>2+</sup> Require Release of Stored Ca<sup>2</sup>.","authors":"Jennifer K Blackburn, Quazi Sufia Islam, Ouafa Benlaouer, Svetlana A Tonevitskaya, Evelina Petitto, Yuri A Ushkaryov","doi":"10.3390/toxins17020073","DOIUrl":"10.3390/toxins17020073","url":null,"abstract":"<p><p>α-Latrotoxin (αLTX) causes exhaustive release of neurotransmitters from nerve terminals in the absence of extracellular Ca<sup>2+</sup> (Ca<sup>2+</sup><sub>e</sub>). To investigate the mechanisms underlying this effect, we loaded mouse neuromuscular junctions with BAPTA-AM. This membrane-permeable Ca<sup>2+</sup>-chelator demonstrates that Ca<sup>2+</sup><sub>e</sub>-independent effects of αLTX require an increase in cytosolic Ca<sup>2+</sup> (Ca<sup>2+</sup><sub>cyt</sub>). We also show that thapsigargin, which depletes Ca<sup>2+</sup> stores, induces neurotransmitter release, but inhibits the effect of αLTX. We then studied αLTX's effects on Ca<sup>2+</sup><sub>cyt</sub> using neuroblastoma cells expressing signaling-capable or signaling-incapable variants of latrophilin-1, a G protein-coupled receptor of αLTX. Our results demonstrate that αLTX acts as a cation ionophore and a latrophilin agonist. In model cells at 0 Ca<sup>2+</sup><sub>e</sub>, αLTX forms membrane pores and allows the influx of Na<sup>+</sup>; this reverses the Na<sup>+</sup>-Ca<sup>2+</sup> exchanger, leading to the release of stored Ca<sup>2+</sup> and inhibition of its extrusion. Concurrently, αLTX stimulates latrophilin signaling, which depletes a Ca<sup>2+</sup> store and induces transient opening of Ca<sup>2+</sup> channels in the plasmalemma that are sensitive to inhibitors of store-operated Ca<sup>2+</sup> entry. These results indicate that Ca<sup>2+</sup> release from intracellular stores and that Ca<sup>2+</sup> influx through latrophilin-activated store-operated Ca<sup>2+</sup> channels contributes to αLTX actions and may be involved in physiological control of neurotransmitter release at nerve terminals.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493528","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}
引用次数: 0
Brown Spider Venom Phospholipases D: From Potent Molecules Involved in Pathogenesis of Brown Spider Bites to Molecular Tools for Studying Ectosomes, Ectocytosis, and Its Applications. 褐蜘蛛毒液磷脂酶D:从参与褐蜘蛛咬伤发病机制的有效分子到研究外胞体、外胞功能及其应用的分子工具。
IF 3.9 3区 医学
Toxins Pub Date : 2025-02-05 DOI: 10.3390/toxins17020070
Ana Carolina Martins Wille, Mariana Izabele Machado, Samira Hajjar Souza, Hanna Câmara da Justa, Maria Eduarda de Fraga-Ferreira, Eloise de Souza Mello, Luiza Helena Gremski, Silvio Sanches Veiga
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