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1.
J Morphol ; 284(1): e21547, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36533732

RESUMO

The mandibular apparatus of batoids (skates, electric rays, guitarfishes, stingrays, and sawfishes) is composed of a few skeletal elements to which the muscular bundles, responsible for all movements involved in the feeding mechanism, are inserted. The description of the different mandibular morphologies can help to understand the different feeding guilds in this group. In this study, we examined the cranio-mandibular myology of adult Rostroraja velezi, Narcine entemedor, and Zapteryx exasperata, three species of rays that coexist in the Southern Gulf of California, Mexico. This study described the muscles on the ventral and the dorsal surfaces for each species, identified the origins and insertions of these muscles, as well as the general characteristics of muscle morphology. There were 17 and 18 muscle bundles attached to the feeding apparatus, including five on the dorsal surface. Only the levator rostri, which elevates the rostrum during feeding, showed considerable differences in shape and size among species. The muscles of the adductor complex showed the greatest differences in size among the three species. N. entemedor presented the exclusive muscle X in the lower mandibular area and the extreme reduction of the coracohyoideus in the pharyngeal area derived from the absence of the basihyal cartilage. The information generated in our study supports the morphological specialization of electric rays (N. entemedor) for an almost exclusive suction feeding strategy.


Assuntos
Rajidae , Animais , México , Rajidae/anatomia & histologia , Mandíbula/anatomia & histologia , Torpedo/anatomia & histologia , Músculo Esquelético/anatomia & histologia
2.
Technol Cult ; 63(4): 1106-1136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341609

RESUMO

Applying a gendered lens to the torpedo boat's adoption (ca. 1860-1900) in the United States and Britain, this article explores the cultural dynamics of military innovation. In the nineteenth century, armored or "ironclad" warships disrupted the ideals of elite "naval manhood": an emphasis inherited from preindustrial officers on physical bravery, seamanship, and endurance. In response, a group of Anglo-American officials, artists, and authors repurposed the torpedo boat to prop up masculine heroism under threat from technical shifts. Ironically, it was a radical technology that preserved old values. This nostalgic effort explains how, in under a generation, the torpedo morphed from an "unchivalrous" weapon into an attractive investment. By refashioning cultural representations of the torpedo boat, advocates both insulated elite "naval manhood" from industrialization and upended modern naval force structures. The adoption of the torpedo boat was as much a gendered reaction to the ironclad revolution as a tactical calculation.


Assuntos
Militares , Navios , Animais , Estados Unidos , Humanos , Torpedo , Reino Unido , Militares/história , Homens
3.
Proc Natl Acad Sci U S A ; 119(34): e2207641119, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969788

RESUMO

Cell membranes are complex assemblies of proteins and lipids making transient or long-term associations that have yet to be characterized at a molecular level. Here, cryo-electron microscopy is applied to determine how phospholipids and cholesterol arrange between neighboring proteins (nicotinic acetylcholine receptors) of Torpedo cholinergic membrane. The lipids exhibit distinct properties in the two leaflets of the bilayer, influenced by the protein surfaces and by differences in cholesterol concentration. In the outer leaflet, the lipids show no consistent motif away from the protein surfaces, in keeping with their assumed fluidity. In the inner leaflet, where the cholesterol concentration is higher, the lipids organize into extensive close-packed linear arrays. These arrays are built from the sterol groups of cholesterol and the initial saturated portions of the phospholipid hydrocarbon chains. Together, they create an ordered ∼7 Å-thick "skin" within the hydrophobic core of the bilayer. The packing of lipids in the arrays appears to bear a close relationship to the linear cholesterol arrays that form crystalline monolayers at the air-water interface.


Assuntos
Membrana Celular , Colesterol , Fosfolipídeos , Animais , Membrana Celular/ultraestrutura , Colesterol/metabolismo , Microscopia Crioeletrônica , Bicamadas Lipídicas , Fluidez de Membrana , Fosfolipídeos/metabolismo , Torpedo
4.
Anal Chim Acta ; 1221: 339941, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934333

RESUMO

The emergent cyclic imine toxins produced by marine dinoflagellates are potent antagonists of nicotinic acetylcholine receptors. Shellfish accumulate cyclic imine toxins following filter-feeding on toxic dinoflagellates vectoring them to humans. Herein is presented a lateral flow test for the detection of cyclic imine toxins based on three new concepts for test strips: i) the immobilization of lipoprotein vesicles in the test-line, ii) the high affinity of neurotoxins for their receptor targets and iii) the use of high porosity glass fiber filter membranes as support for the fabrication of the lateral flow test NeuroTorp (WO2017108115). Purified electrocyte membrane vesicles from Torpedo marmorata were used as a source of receptor and were immobilized in the test-line. Biotin-α-bungarotoxin was used as toxin tracer for the NeuroTorp LFT given its high affinity for nicotinic acetylcholine receptors while neutravidin nanogold particle conjugates enable its visual detection. Herein is reported for the first time the use of GF/C glass fiber membranes as the stationary phase for a lateral flow test. The GF/C filter ensures both: the immobilization of a complex lipoprotein in the test-line and the capillary migration of the mobile phase. Scanning electron microscopy studies shed light into the mechanism by which Torpedo-electrocyte membranes vesicles are immobilized in the GF/C glass microfiber. The electrocyte membrane vesicles anchor in neighboring microfibers randomly disposed in the same plane of the GF/C filter forming stable microfilm structures ensuring the functionality of nicotinic acetylcholine receptors. NeuroTorp is a ready-to-use low-cost early warning device for rapid detection of cyclic imine toxins in shellfish by end-users.


Assuntos
Receptores Nicotínicos , Toxinas Biológicas , Animais , Proteínas de Transporte/química , Iminas/toxicidade , Frutos do Mar , Torpedo
5.
J Mol Graph Model ; 116: 108265, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35816907

RESUMO

Acetylcholinesterase (AChE) is the object of many studies due to the fact that it plays an important role in the vital activity of organisms. In particular, when new AChE inhibitors are developed, much attention is paid to the specificity of their action. One of the approaches used to study the specificity is to compare AChE taken from various organisms. In this work, crystallographic data are used to investigate the active sites of AChE (ASAs) in the free (uncomplexed) state for the following five organisms: Homo sapiens (HS), Mus musculus (MM), Torpedo californica (TC), Electrophorus electricus (EE), and Drosophila melanogaster (DM). The structural fractal analysis (SFA) proposed by us earlier is used as a research method. This method is based on the calculation and comparison of the fractal dimensions of molecular structures. SFA demonstrates that there are no significant structural differences between the active sites of human AChE and other AChEs. However, differences are found for the MM/EE pair. Further analysis of individual AARs has revealed two different areas of active sites. Ser203, Trp236, Phe338, and Tyr341 are found to belong to a variable region, and the remaining AARs belong to a conservative region of the ASAs. The fraction of "variability" is low, 0.8%.


Assuntos
Acetilcolinesterase , Fractais , Acetilcolinesterase/química , Animais , Domínio Catalítico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Drosophila melanogaster , Electrophorus/metabolismo , Humanos , Camundongos , Torpedo/metabolismo
6.
J Membr Biol ; 255(4-5): 563-574, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35534578

RESUMO

Erwin London dedicated considerable effort to understanding lipid interactions with membrane-resident proteins and how these interactions shaped the formation and maintenance of lipid phases and domains. In this endeavor, he developed ad hoc techniques that greatly contributed to advancements in the field. We have employed and/or modified/extended some of his methodological approaches and applied them to investigate lipid interaction with the nicotinic acetylcholine receptor (nAChR) protein, the paradigm member of the superfamily of rapid pentameric ligand-gated ion channels (pLGIC). Our experimental systems ranged from purified receptor protein reconstituted into synthetic lipid membranes having known effects on receptor function, to cellular systems subjected to modification of their lipid content, e.g., varying cholesterol levels. We have often employed fluorescence techniques, including fluorescence quenching of diphenylhexatriene (DPH) extrinsic fluorescence and of nAChR intrinsic fluorescence by nitroxide spin-labeled phospholipids, DPH anisotropy, excimer formation of pyrene-phosphatidylcholine, and Förster resonance energy transfer (FRET) from the protein moiety to the extrinsic probes Laurdan, DPH, or pyrene-phospholipid to characterize various biophysical properties of lipid-receptor interactions. Some of these strategies are revisited in this review. Special attention is devoted to the anionic phospholipid phosphatidic acid (PA), which stabilizes the functional resting form of the nAChR. The receptor protein was shown to organize its PA-containing immediate microenvironment into microdomains with high lateral packing density and rigidity. PA and cholesterol appear to compete for the same binding sites on the nAChR protein.


Assuntos
Canais Iônicos de Abertura Ativada por Ligante , Receptores Nicotínicos , Animais , Receptores Nicotínicos/química , Torpedo/metabolismo , Difenilexatrieno , Londres , Fosfatidilcolinas/metabolismo , Colesterol/química , Ácidos Fosfatídicos/metabolismo , Pirenos
7.
Mar Pollut Bull ; 177: 113569, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35334308

RESUMO

This study comprises a novel report on subcellular metal partitioning and metallothionein (MT) metal detoxification efforts in lesser numbfish (Narcine brasiliensis) electric ray specimens, as well as the first assessment on MT contents in any ray electric organ. Individuals sampled from an area in Southeastern Brazil affected by the Mariana dam rupture disaster were assessed concerning subcellular metal partitioning and MT metal-detoxification in the liver, gonads, electric organ and muscle of both adults and embryos. Yolk was also assessed when available. Relative total and heat-stable (bioavailable) metal and metalloid comparisons between adults and embryos in different developmental stages demonstrates maternal transfer of both total and bioavailable metals and significant MT associations demonstrate the detoxification of As, Ag, Mn, Ni, Cd, Co, Cu, Se and V through this biochemical pathway. Our findings expand the lacking ecotoxicological assessments for this near-threatened species and indicates significant ecological concerns, warranting further biomonitoring efforts.


Assuntos
Desastres , Poluentes Químicos da Água , Animais , Brasil , Metais/metabolismo , Torpedo/metabolismo , Poluentes Químicos da Água/química
8.
Nat Struct Mol Biol ; 29(4): 386-394, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35301478

RESUMO

Binding of the neurotransmitter acetylcholine to its receptors on muscle fibers depolarizes the membrane and thereby triggers muscle contraction. We sought to understand at the level of three-dimensional structure how agonists and antagonists alter nicotinic acetylcholine receptor conformation. We used the muscle-type receptor from the Torpedo ray to first define the structure of the receptor in a resting, activatable state. We then determined the receptor structure bound to the agonist carbachol, which stabilizes an asymmetric, closed channel desensitized state. We find conformational changes in a peripheral membrane helix are tied to recovery from desensitization. To probe mechanisms of antagonism, we obtained receptor structures with the active component of curare, a poison arrow toxin and precursor to modern muscle relaxants. d-Tubocurarine stabilizes the receptor in a desensitized-like state in the presence and absence of agonist. These findings define the transitions between resting and desensitized states and reveal divergent means by which antagonists block channel activity of the muscle-type nicotinic receptor.


Assuntos
Curare , Receptores Nicotínicos , Animais , Sítios de Ligação , Curare/metabolismo , Músculos/metabolismo , Receptores Nicotínicos/química , Receptores Nicotínicos/metabolismo , Torpedo/metabolismo
9.
Neuron ; 110(8): 1358-1370.e5, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35139364

RESUMO

Fast synaptic communication requires receptors that respond to the presence of neurotransmitter by opening an ion channel across the post-synaptic membrane. The muscle-type nicotinic acetylcholine receptor from the electric fish, Torpedo, is the prototypic ligand-gated ion channel, yet the structural changes underlying channel activation remain undefined. Here we use cryo-EM to solve apo and agonist-bound structures of the Torpedo nicotinic receptor embedded in a lipid nanodisc. Using both a direct biochemical assay to define the conformational landscape and molecular dynamics simulations to assay flux through the pore, we correlate structures with functional states and elucidate the motions that lead to pore activation of a heteromeric nicotinic receptor. We highlight an underappreciated role for the complementary subunit in channel gating, establish the structural basis for the differential agonist affinities of α/δ versus α /γ sites, and explain why nicotine is less potent at muscle nicotinic receptors compared to neuronal ones.


Assuntos
Canais Iônicos de Abertura Ativada por Ligante , Receptores Nicotínicos , Animais , Sítios de Ligação , Canais Iônicos de Abertura Ativada por Ligante/metabolismo , Ligantes , Músculos , Receptores Nicotínicos/metabolismo , Torpedo/metabolismo
10.
Microscopy (Oxf) ; 71(Supplement_1): i66-i71, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-34226930

RESUMO

Many new structures of membrane proteins have been determined over the last decade, yet the nature of protein-lipid interplay has received scant attention. The postsynaptic membrane of the neuromuscular junction and Torpedo electrocytes has a regular architecture, opening an opportunity to illuminate how proteins and lipids act together in a native membrane setting. Cryo electron microscopy (Cryo-EM) images show that cholesterol segregates preferentially around the constituent ion channel, the nicotinic acetylcholine receptor, interacting with specific sites in both leaflets of the bilayer. In addition to maintaining the transmembrane α-helical architecture, cholesterol forms microdomains - bridges of rigid sterol groups that link one channel to the next. This article discusses the whole protein-lipid organization of the cholinergic postsynaptic membrane, its physiological implications and how the observed details relate to our current concept of the membrane structure. I suggest that cooperative interactions, facilitated by the regular protein-lipid arrangement, help to spread channel activation into regions distant from the sites of neurotransmitter release, thereby enhancing the postsynaptic response.


Assuntos
Receptores Nicotínicos , Animais , Membrana Celular/metabolismo , Colesterol , Junção Neuromuscular/metabolismo , Receptores Nicotínicos/química , Receptores Nicotínicos/metabolismo , Torpedo/metabolismo
11.
Integr Zool ; 17(2): 234-245, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33728755

RESUMO

Members of the Torpedinidae (torpedoes) and Hypnidae (coffin ray) use electric organ discharges (EOD) to stun or kill their prey before consumption. We investigated whether EOD could also negatively affect the helminth larvae infecting these preys through a surrogate model: we applied electric discharges to individuals of blue whiting, Micromesistius poutassou, that harbored live larvae of Anisakis. Larval mortality throughout a 6-h period was significantly higher in the treatment group, suggesting that EODs could significantly hamper helminth recruitment. We then tested whether torpedinids and hypnids ("strong-EOD" families) harbored species-poor helminth (cestode) assemblages compared with "weak-EOD" Torpediniformes (Narcidae and Narkidae) and other Batoidea. Based on comparisons on estimated species diversity and mean species richness of tapeworms at host individual level we found that (i) Torpediniformes had the lowest tapeworm diversity of all Batoidea orders; (ii) Torpedo spp. consistently had the lowest mean cestode richness at host individual level, and this could not be related to other host factors influencing cestode diversity in chondrichthyans, that is body size, trophic level or dietary breath. However, a preliminary comparison between "strong-EOD" and "weak-EOD" Torpediniformes did not detect clear differences of cestode richness. Thus, evidence supporting an unambiguous contribution of EODs to depauperate cestode assemblages requires further research.


Assuntos
Órgão Elétrico , Cadeia Alimentar , Parasitos , Torpedo/parasitologia , Animais , Larva/parasitologia
12.
Eur J Med Chem ; 227: 113947, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34731766

RESUMO

Triterpenoic acids (oleanolic, ursolic, betulinic, platanic and glycyrrhetinic acid) were acetylated and coupled with 1,3- or 1,4-diazabicyclo[3.2.2]nonanes to yield amides. Reaction of these amides with methyl iodide at the distal nitrogen of the bicyclic system gave the corresponding quaternary ammonium salts. These compounds were shown to act as excellent inhibitors of the enzyme butyrylcholinesterase (BChE) while being only weak inhibitors for acetylcholinesterase (AChE). Evaluation of the enzyme kinetics revealed these compounds to act as hyperbolic inhibitors for BChE while the results from molecular modeling gave an explanation for their selectivity between AChE and BChE.


Assuntos
Compostos Aza/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/química , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Triterpenos/farmacologia , Acetilcolinesterase/metabolismo , Animais , Compostos Aza/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Electrophorus , Humanos , Metilação , Estrutura Molecular , Relação Estrutura-Atividade , Torpedo , Triterpenos/síntese química , Triterpenos/química
13.
Mol Pharmacol ; 101(3): 154-167, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34969831

RESUMO

Alzheimer's disease is a multifactorial neurodegenerative disorder. Since cholinergic deficit is a major factor in this disease, two molecular targets for its treatment are the acetylcholinesterase (AChE) and the nicotinic acetylcholine receptors (nAChRs). Given that caffeine is a natural compound that behaves as an AChE inhibitor and as a partial agonist of nAChRs, the aim of this work was to synthetize more potent bifunctional caffeine analogs that modulate these two molecular targets. To this end, a theophylline structure was connected to a pyrrolidine structure through a methylene chain of different lengths (3 to 7 carbon atoms) to give compounds 7-11 All caffeine derivatives inhibited the AChE, of which compound 11 showed the strongest effect. Electrophysiological studies showed that all compounds behave as agonists of the muscle and the neuronal α7 nAChR with greater potency than caffeine. To explore whether the different analogs could affect the nAChR conformational state, the nAChR conformational-sensitive probe crystal violet (CrV) was used. Compounds 9 and 10 conduced the nAChR to a different conformational state comparable with a control nAChR desensitized state. Finally, molecular docking experiments showed that all derivatives interacted with both the catalytic and anionic sites of AChE and with the orthosteric binding site of the nAChR. Thus, the new synthetized compounds can inhibit the AChE and activate muscle and α7 nAChRs with greater potency than caffeine, which suggests that they could be useful leaders for the development of new therapies for the treatment of different neurologic diseases. SIGNIFICANCE STATEMENT: In this work we synthetized caffeine derivatives which can inhibit acetylcholinesterase and activate both muscle and α7 nicotinic acetylcholine receptors (nAChRs) with higher potency than caffeine. These analogs can be divided into two groups: a non-desensitizing and a desensitizing nAChR group. From the nAChR non-desensitizing group, we propose compound 11 as the most interesting analog for further studies since it inhibits acetylcholinesterase with the highest potency and activates the nAChRs in the picomolar range without inducing receptor desensitization.


Assuntos
Cafeína/análogos & derivados , Cafeína/síntese química , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Animais , Cafeína/metabolismo , Cafeína/farmacologia , Electrophorus , Células HEK293 , Humanos , Simulação de Acoplamento Molecular/métodos , Estrutura Secundária de Proteína , Torpedo , Receptor Nicotínico de Acetilcolina alfa7/química
14.
Methods Enzymol ; 653: 189-206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34099171

RESUMO

Nicotinic acetylcholine receptors are members of the Cys-loop superfamily of pentameric ligand-gated ion channels. The electric organ of the Torpedo ray is extraordinarily rich in an acetylcholine receptor that is homologous to the human nicotinic receptor found at the neuromuscular junction. Due to this abundant natural source in the fish and the relatively accessible preparation of the neuromuscular junction (compared to a central synapse), this muscle-type receptor and specifically the fish receptors have long been used as the prototype for study of nicotinic receptors. However, an absence of structural detail at high resolution has limited the chemical interpretation of this archetypal nicotinic receptor. One of the main concerns in preparing receptor for high resolution structural analysis was its documented sensitivity to particular detergents and requirements for specific lipids in order to maintain function after reconstitution in a membrane. Here, we present methods for purifying native nicotinic receptor from Torpedo electric tissue that maintains functionality after reconstitution and that is amenable to high resolution structural analysis. The specific developments we describe include detergent exchange during purification, inclusion of specific lipids during purification and for nanodisc reconstitution, and synthesis of a new affinity reagent for rapid isolation of receptors.


Assuntos
Canais Iônicos de Abertura Ativada por Ligante , Receptores Nicotínicos , Torpedo , Animais , Proteínas de Peixes/isolamento & purificação , Canais Iônicos de Abertura Ativada por Ligante/isolamento & purificação , Receptores Nicotínicos/isolamento & purificação
15.
Viruses ; 13(4)2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807136

RESUMO

Rubella virus (RuV) is the causative agent of rubella ("German measles") and remains a global health concern. Until recently, RuV was the only known member of the genus Rubivirus and the only virus species classified within the Matonaviridae family of positive-sense RNA viruses. Recently, two new rubella-like matonaviruses, Rustrela virus and Ruhugu virus, have been identified in several mammalian species, along with more divergent viruses in fish and reptiles. To screen for the presence of additional novel rubella-like viruses, we mined published transcriptome data using genome sequences from Rubella, Rustrela, and Ruhugu viruses as baits. From this, we identified a novel rubella-like virus in a transcriptome of Tetronarce californica-order Torpediniformes (Pacific electric ray)-that is more closely related to mammalian Rustrela virus than to the divergent fish matonavirus and indicative of a complex pattern of cross-species virus transmission. Analysis of host reads confirmed that the sample analysed was indeed from a Pacific electric ray, and two other viruses identified in this animal, from the Arenaviridae and Reoviridae, grouped with other fish viruses. These findings indicate that the evolutionary history of the Matonaviridae is more complex than previously thought and highlights the vast number of viruses that remain undiscovered.


Assuntos
Bases de Dados de Ácidos Nucleicos , Evolução Molecular , Filogenia , Rubivirus/classificação , Rubivirus/genética , Torpedo/virologia , Animais , Arenaviridae/genética , Mineração de Dados , Feminino , Perfilação da Expressão Gênica , Reoviridae/genética , Vírus da Rubéola/genética , Rubivirus/isolamento & purificação
16.
Protein Sci ; 30(5): 966-981, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33686648

RESUMO

Stabilization of Torpedo californica acetylcholinesterase by the divalent cations Ca+2 , Mg+2 , and Mn+2 was investigated. All three substantially protect the enzyme from thermal inactivation. Electron paramagnetic resonance revealed one high-affinity binding site for Mn+2 and several much weaker sites. Differential scanning calorimetry showed a single irreversible thermal transition. All three cations raise both the temperature of the transition and the activation energy, with the transition becoming more cooperative. The crystal structures of the Ca+2 and Mg+2 complexes with Torpedo acetylcholinesterase were solved. A principal binding site was identified. In both cases, it consists of four aspartates (a 4D motif), within which the divalent ion is embedded, together with several water molecules. It makes direct contact with two of the aspartates, and indirect contact, via waters, with the other two. The 4D motif has been identified in 31 acetylcholinesterase sequences and 28 butyrylcholinesterase sequences. Zebrafish acetylcholinesterase also contains the 4D motif; it, too, is stabilized by divalent metal ions. The ASSAM server retrieved 200 other proteins that display the 4D motif, in many of which it is occupied by a divalent cation. It is a very versatile motif, since, even though tightly conserved in terms of RMSD values, it can contain from one to as many as three divalent metal ions, together with a variable number of waters. This novel motif, which binds primarily divalent metal ions, is shared by a broad repertoire of proteins. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:Protein_Science:3.


Assuntos
Acetilcolinesterase/química , Proteínas de Peixes/química , Torpedo , Animais , Sítios de Ligação , Cátions Bivalentes/química , Cristalografia por Raios X , Estabilidade Enzimática , Metais/química
17.
Toxins (Basel) ; 13(2)2021 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672715

RESUMO

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.


Assuntos
Colinérgicos/farmacologia , Proteínas Neurotóxicas de Elapídeos/farmacologia , Venenos Elapídicos/metabolismo , Antagonistas de Receptores de GABA-A/farmacologia , Naja , Receptores de GABA/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/efeitos dos fármacos , Animais , Sítios de Ligação , Ligação Competitiva , Linhagem Celular Tumoral , Colinérgicos/metabolismo , Proteínas Neurotóxicas de Elapídeos/metabolismo , Antagonistas de Receptores de GABA-A/metabolismo , Potenciais da Membrana , Camundongos , Ligação Proteica , Conformação Proteica , Receptores de GABA/genética , Receptores de GABA/metabolismo , Relação Estrutura-Atividade , Torpedo , Xenopus laevis , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
18.
J Fish Biol ; 99(2): 437-449, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33759180

RESUMO

In the study, the authors evaluate the spatial distribution pattern of vermiculate electric-ray Narcine vermiculatus using geostatistical techniques to predict its spatial distribution and indicate its reproduction strategy. From January 2008 to December 2009, 3333 specimens of vermiculate electric-ray were caught. Total length (LT ), sex, maturity stage, catch location and depth were recorded for each specimen. The LT of vermiculate electric-ray ranged from 6.7-24.6 cm. The authors estimate an irregular spatial structure, with a high-density patch ( x ¯ = 53 ind. ha-1 ) located on the east coast, which concentrates 65.2% of the specimens. The high-density patch consists mainly of large juveniles (13.3-19.5 cm LT ), sub-adults (14.0-19.8 cm LT ) and young adults (14.7-21.3 cm LT ). Data indicate that adults migrate to the high-density patch to reproduce. Males reached maturity at 14.5 cm LT , whereas females reached maturity at 19.3 cm LT . Vitellogenesis in female vermiculate electric-ray begins in June; ovulation, mating, fertilization and gestation in October and birth begins in February. This indicates an annual cycle with vitellogenesis and consecutive gestation, in females synchronized in reproduction. Fecundity was 1-8 ( x ¯ = 4), and the sex ratio of embryos was 1:1. The birth occurred between February and April, with an average size at parturition of 6.3 cm LT . Incidental capture of sub-adults and adults of N. vermiculatus by bottom trawls threatens the survival of this species.


Assuntos
Elasmobrânquios , Reprodução , Animais , Feminino , Fertilidade , Masculino , Estações do Ano , Razão de Masculinidade , Torpedo
19.
Med Chem ; 17(5): 442-452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31808389

RESUMO

BACKGROUND: Chalcones, originated from natural product, have been broadly studied their biological activity against various proteins which at the molecular level, are responsible for the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis (cathepsins receptor), and diabetes (e.g. α-glucosidase). OBJECTIVE: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). METHODS: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay was conducted using Ellman Method. RESULTS: Compounds 2b and 4b demonstrated as the best IC50 of 9.3 µM and 68.7 µM respectively, towards AChE and BChE inhibition. Molecular docking studies predicted that this activity might be due to the interaction of the chalcones with important amino acid residues in the binding site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440, LEU286 and VAL288. CONCLUSION: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic chain is necessary at the meta-position of Ring B.


Assuntos
Chalconas/química , Inibidores da Colinesterase/química , Acetilcolinesterase/metabolismo , Animais , Butirilcolinesterase/metabolismo , Chalconas/síntese química , Chalconas/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/metabolismo , Ensaios Enzimáticos , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , Torpedo
20.
J Morphol ; 282(3): 438-448, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33377231

RESUMO

Torpediniformes (electric rays) is a monophyletic group strongly supported by morphological and molecular phylogenetic studies. The claspers of electric rays, however, are poorly documented in comparation to the clasper of other batoids, especially skates, and the knowledge of their anatomical variation is restricted to the description of a few species. The present article analyzes the external and skeletal clasper anatomy of electric rays and reports newly discovered characters that can be useful for taxonomic diagnoses and higher-level systematic studies. The family Torpedinidae exclusively presents the integumental flap, a poorly calcified clasper skeleton, and a dorsal marginal cartilage with a medial flange on its distal portion. Derived or diagnostic characters were not found in the clasper of the reportedly nonmonophyletic families Narcinidae and Narkidae; however, the claspers of species and genera of narcinids and narkids present different anatomical patterns that can be useful for taxonomic and phylogenetic studies.


Assuntos
Estruturas Animais/anatomia & histologia , Filogenia , Torpedo/anatomia & histologia , Torpedo/classificação , Animais , Cartilagem/anatomia & histologia
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