المؤلفون: Sandra Gegunde, Luis M. Botana, Amparo Alfonso, Rebeca Alvariño, Eva Alonso

المصدر: Cellular and Molecular Neurobiology. 40:603-615

مصطلحات موضوعية: Lipopolysaccharides, 0301 basic medicine, Lipopolysaccharide, Cell Survival, NF-E2-Related Factor 2, medicine.drug_class, Anti-Inflammatory Agents, Nitric Oxide Synthase Type II, Inflammation, Nitric Oxide, Anti-inflammatory, Cell Line, Nitric oxide, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Humans, Cyclophilin, Membrane Potential, Mitochondrial, biology, Microglia, Interleukin-6, Tumor Necrosis Factor-alpha, NF-kappa B, Cell Biology, General Medicine, Nitric oxide synthase, 030104 developmental biology, medicine.anatomical_structure, chemistry, Biochemistry, Cyclosporine, biology.protein, Tumor necrosis factor alpha, Diterpenes, medicine.symptom, Reactive Oxygen Species, 030217 neurology & neurosurgery

الوصف: Gracilins are diterpenes derivative, isolated from the marine sponge Spongionella gracilis. Natural gracilins and synthetic derivatives have shown antioxidant, immunosuppressive, and neuroprotective capacities related to the affinity for cyclophilins. The aim of this work was to study anti-inflammatory and immunosuppressive pathways modulated by gracilin L and two synthetic analogues, compound 1 and 2, on a cellular model of inflammation. In this way, the murine BV2 microglia cell line was used. To carry out the experiments, microglia cells were pre-treated with compounds for 1 h and then stimulated with lipopolysaccharide for 24 h to determine reactive oxygen species production, mitochondrial membrane potential, the release of nitric oxide, interleukin-6 and tumor necrosis factor-α and the expression of Nuclear factor-erythroid 2-related factor 2, Nuclear Factor-κB, the inducible nitric oxide synthase, and the cyclophilin A. Finally, a co-culture of neuron SH-SY5Y and microglia BV2 cells was used to check the neuroprotective effect of these compounds. Cyclosporine A was used as a control of effect. The compounds were able to decrease inflammatory mediators, the expression of inflammatory target proteins as well as they activated anti-oxidative mechanism upon inflammatory conditions. For this reason, natural and synthetic gracilins could be interesting for developing anti-inflammatory drugs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24dc28c8c10218eaac99420b149d9e8cTest
https://doi.org/10.1007/s10571-019-00758-5Test

المؤلفون: N Fol Rodríguez, A Lozano-Leon, Mercedes R. Vieytes, R Rodriguez-Souto, Juan A. Rubiolo, Luis M. Botana

المصدر: Antonie van Leeuwenhoek. 111:1117-1129

مصطلحات موضوعية: 0301 basic medicine, Microorganism, 030106 microbiology, Hepatopancreas, Zoology, Biology, Microbiology, 03 medical and health sciences, Animals, Molecular Biology, Shellfish, Bacteria, food and beverages, Bacteriome, Biodiversity, General Medicine, Mussel, Human decontamination, biology.organism_classification, Bivalvia, 030104 developmental biology, Metagenome, Pyrosequencing, Genome, Bacterial

الوصف: Due to the rapid elimination of bacteria through normal behaviour of filter feeding and excretion, the decontamination of hazardous contaminating bacteria from shellfish is performed by depuration. This process, under conditions that maximize shellfish filtering activity, is a useful method to eliminate microorganisms from bivalves. The microbiota composition in bivalves reflects that of the environment of harvesting waters, so quite different bacteriomes would be expected in shellfish collected in different locations. Bacterial accumulation within molluscan shellfish occurs primarily in the hepatopancreas. In order to assess the effect of the depuration process on these different bacteriomes, in this work we used 16S RNA pyrosequencing and metagenome prediction to assess the impact of 15 h of depuration on the whole hepatopancreas bacteriome of mussels collected in three different locations.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b65a771ae92954a9e38e7ca4b8fb5230Test
https://doi.org/10.1007/s10482-018-1015-yTest

المؤلفون: Cristina Carrera, Sara F. Ferreiro, Luis M. Botana, J. Manuel Cifuentes, Antonio González Cantalapiedra, Andrés Crespo, M. Carmen Louzao, Natalia Vilariño, Germán Santamarina

المصدر: Archives of Toxicology. 91:1859-1870

مصطلحات موضوعية: 0301 basic medicine, Programmed cell death, Time Factors, Health, Toxicology and Mutagenesis, Blotting, Western, Mollusk Venoms, Apoptosis, Biology, Toxicology, Fas ligand, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, In vivo, Autophagy, Animals, Azaspiracid, Myocytes, Cardiac, Spiro Compounds, Oxocins, General Medicine, Rats, Cell biology, Toxicity Tests, Subacute, 030104 developmental biology, chemistry, Female, Marine Toxins, Yessotoxin, Marine toxin, Biomarkers

الوصف: Yessotoxins (YTX) and azaspiracids (AZAs) are marine toxins produced by phytoplanktonic dinoflagellates that get accumulated in filter feeding shellfish and finally reach human consumers through the food web. Both toxin classes are worldwide distributed, and food safety authorities have regulated their content in shellfish in many countries. Recently, YTXs and AZAs have been described as compounds with subacute cardiotoxic potential in rats owed to alterations of the cardiovascular function and ultrastructural heart damage. These molecules are also well known in vitro inducers of cell death. The aim of this study was to explore the presence of cardiomyocyte death after repeated subacute exposure of rats to AZA-1 and YTX for 15 days. Because autophagy and apoptosis are often found in dying cardiomyocytes, several autophagic and apoptotic markers were determined by western blot in heart tissues of these rats. The results showed that hearts from YTX-treated rats presented increased levels of the autophagic markers microtubule-associated protein light chain 3-II (LC3-II) and beclin-1, nevertheless AZA-1-treated hearts evidenced increased levels of the apoptosis markers cleaved caspase-3 and -8, cleaved PARP and Fas ligand. Therefore, while YTX-induced damage to the heart triggers autophagic processes, apoptosis activation occurs in the case of AZA-1. For the first time, activation of cell death signals in cardiomyocytes is demonstrated for these toxins with in vivo experiments, which may be related to alterations of the cardiovascular function.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b11327c54d07f1455e445a60ecb1cbbTest
https://doi.org/10.1007/s00204-016-1862-0Test

المؤلفون: Amparo Alfonso, Luis M. Botana, Eva Alonso, Mercedes R. Vieytes

المصدر: Archives of Toxicology. 90:479-488

مصطلحات موضوعية: 0301 basic medicine, Patch-Clamp Techniques, Health, Toxicology and Mutagenesis, Computational biology, Biology, Toxicology, 01 natural sciences, Sodium Channels, 03 medical and health sciences, chemistry.chemical_compound, Automated patch clamp, medicine, Humans, Shellfish Poisoning, Paralytic shellfish poisoning, Throughput (business), Saxitoxin, Dose-Response Relationship, Drug, Sodium channel, 010401 analytical chemistry, General Medicine, medicine.disease, High-Throughput Screening Assays, 0104 chemical sciences, Electrophysiology, HEK293 Cells, 030104 developmental biology, chemistry, Toxicity, Marine Toxins, Marine toxin

الوصف: Although voltage-gated sodium channels (Na v ) are the cellular target of paralytic shellfish poisoning (PSP) toxins and that patch clamp electrophysiology is the most effective way of studying direct interaction of molecules with these channels, nowadays, this technique is still reduced to more specific analysis due to the difficulties of transforming it in a reliable throughput system. Actual functional methods for PSP detection are based in binding assays using receptors but not functional Na v channels. Currently, the availability of automated patch clamp platforms and also of stably transfected cell lines with human Na v channels allow us to introduce this specific and selective method for fast screenings in marine toxin detection. Taking advantage of the accessibility to pure PSP standards, we calculated the toxicity equivalent factors (TEFs) for nine PSP analogs obtaining reliable TEFs in human targets to fulfill the deficiencies of the official analytic methods and to verify automated patch clamp technology as a fast and reliable screening method for marine toxins that interact with the sodium channel. The main observation of this work was the large variation of TEFs depending on the channel subtype selected, being remarkable the variation of potency in the 1.7 channel subtype and the suitability of Na v 1.6 and 1.2 channels for PSP screening.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f7272db5120953d256749388571daa1Test
https://doi.org/10.1007/s00204-014-1444-yTest

المؤلفون: Natalia Vilariño, Luis M. Botana, Michael O. Frederick, Andrés C. Vieira, Sara F. Ferreiro, Germán Santamarina, Antonio González Cantalapiedra, Kyriacos C. Nicolaou, Cristina Carrera, Laura Rodríguez, M. Carmen Louzao, J. Manuel Cifuentes

المصدر: Archives of Toxicology. 88:425-434

مصطلحات موضوعية: ERG1 Potassium Channel, Patch-Clamp Techniques, Health, Toxicology and Mutagenesis, hERG, ved/biology.organism_classification_rank.species, CHO Cells, Pharmacology, Toxicology, Azadinium spinosum, QT interval, Article, Rats, Sprague-Dawley, Electrocardiography, Cricetulus, In vivo, Potassium Channel Blockers, medicine, Animals, Azaspiracid, heterocyclic compounds, Furans, neoplasms, Pyrans, Cardiotoxicity, biology, ved/biology, Myocardium, Arrhythmias, Cardiac, Potassium channel blocker, General Medicine, Ether-A-Go-Go Potassium Channels, Potassium channel, Rats, stomatognathic diseases, biology.protein, Female, Biomarkers, medicine.drug

الوصف: Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellate Azadinium spinosum that accumulate in several shellfish species. Azaspiracid poisoning (AZP) episodes have been described in humans due to ingestion of AZA-contaminated seafood. Therefore, the contents of AZA-1, AZA-2 and AZA-3, the best-known analogs of the group, in shellfish destined to human consumption have been regulated by food safety authorities of many countries to protect human health. In vivo and in vitro toxicological studies have described effects of AZAs at different cellular levels and on several organs, however, AZA target remains unknown. Very recently AZAs have been demonstrated to block the hERG cardiac potassium channel. In this study we explored the potential cardiotoxicity of AZA-2 in vivo. The effects of AZA-2 on rat electrocardiogram (ECG) and cardiac biomarkers were evaluated for cardiotoxicity signs besides corroborating the hERG blocking activity of AZA-2. Our results demonstrated that AZA-2 does not induce QT interval prolongation on rat ECGs in vivo, in spite of being an in vitro blocker of the hERG cardiac potassium channel. However, AZA-2 alters the heart electrical activity causing prolongation of PR intervals and the appearance of arrhythmias. More studies will be needed to clarify the mechanism by which AZA-2 causes these ECG alterations, however, the potential cardiotoxicity of AZAs demonstrated in this in vivo study should be taken into consideration when evaluating the possible threat that these toxins pose to human health, mainly for individuals with pre-existing cardiovascular disease when regulated toxin limits are exceeded.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b6e2932e4f98d6727484832b6194fa1Test
https://doi.org/10.1007/s00204-013-1115-4Test

المؤلفون: Luis M. Botana, Carmen Vale, Eva Alonso, Juan A. Rubiolo, Frank M. LaFerla, Lydia Giménez-Llort, Mercedes R. Vieytes

المصدر: Cellular and Molecular Neurobiology. 30:577-590

مصطلحات موضوعية: Transgene, Immunocytochemistry, Glutamic Acid, Mice, Transgenic, tau Proteins, Amyloid beta-Protein Precursor, Mice, Cellular and Molecular Neuroscience, Western blot, Alzheimer Disease, Amyloid precursor protein, medicine, Animals, Homeostasis, Humans, Phosphorylation, Cells, Cultured, Cerebral Cortex, Neurons, Amyloid beta-Peptides, biology, medicine.diagnostic_test, Cell Biology, General Medicine, medicine.disease, Acetylcholine, In vitro, Cell biology, Disease Models, Animal, medicine.anatomical_structure, Cerebral cortex, biology.protein, Cholinergic, Calcium, Alzheimer's disease, Neuroscience

الوصف: Advances in transgenic technology as well as in the genetics of Alzheimer disease (AD) have allowed the establishment of animal models that reproduce amyloid-beta plaques and neurofibrillary tangles, the main pathological hallmarks of AD. Among these models, 3xTg-AD mice harboring PS1 (M146V), APP (Swe) and tau (P301L) human transgenes provided the model that most closely mimics human AD features. Although cortical cultures from 3xTg-AD mice have been shown to present disturbances in intracellular [Ca(2+)] homeostasis, the development of AD pathology in vitro has not been previously evaluated. In the current work, we determined the temporal profile for amyloid precursor protein, amyloid-beta and tau expression in primary cortical cultures from 3xTg-AD mice. Immunocytochemistry and Western blot analysis showed an increased expression of these proteins as well as several phosphorylated tau isoforms with time in culture. Alterations in calcium homeostasis and cholinergic and glutamatergic responses were also observed early in vitro. Thus, 3x-TgAD cortical neurons in vitro provide an exceptional tool to investigate pharmacological approaches as well as the cellular basis for AD and related diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3af65ca592db36ec47ac7e9c3be25bccTest
https://doi.org/10.1007/s10571-009-9482-3Test