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Spider-derived peptides with insecticidal, antimicrobial and/or cytolytic activities, also known as spider venom antimicrobial peptides (AMPs), can be found in the venoms of RTA-clade spiders. They show translational potential as therapeutic leads. A set of 52 AMPs has been described in the Chinese wolf spider (Lycosa shansia), and many have been shown to exhibit antibacterial effects. Here we explored the potential to enhance their antimicrobial activity using bioengineering. We generated a panel of artificial derivatives of an A-family peptide and screened their activity against selected microbial pathogens, vertebrate cells and insects. In several cases, we increased the antimicrobial activity of the derivatives while retaining the low cytotoxicity of the parental molecule. Furthermore, we injected the peptides into adult Drosophila suzukii and found no evidence of insecticidal effects, confirming the low levels of toxicity. Our data therefore suggest that spider venom linear peptides naturally defend the venom gland against microbial colonization and can be modified into more potent antimicrobial agents that could help to battle infectious diseases in the future.
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Venenos de Araña , Arañas , Animales , Venenos de Araña/química , Venenos de Araña/farmacología , Venenos de Araña/toxicidad , Drosophila/efectos de los fármacos , Péptidos Antimicrobianos/farmacología , Antiinfecciosos/farmacología , Insecticidas/farmacología , HumanosRESUMEN
Polyamines (PAs) are polycationic biogenic amines ubiquitously present in all life forms and are involved in molecular signaling and interaction, determining cell fate (e.g., cell proliferation, dif-ferentiation, and apoptosis). The intricate balance in the PAs' levels in the tissues will determine whether beneficial or detrimental effects will affect homeostasis. It's crucial to note that endoge-nous polyamines, like spermine and spermidine, play a pivotal role in our understanding of neu-rological disorders as they interact with membrane receptors and ion channels, modulating neuro-transmission. In spiders and wasps, monoamines (histamine, dopamine, serotonin, tryptamine) and polyamines (spermine, spermidine, acyl polyamines) comprise, with peptides and other sub-stances, the low molecular weight fraction of the venom. Acylpolyamines are venom components exclusively from spiders and a species of solitary wasp, which cause inhibition chiefly of iono-tropic glutamate receptors (AMPA, NMDA, and KA iGluRs) and nicotinic acetylcholine receptors (nAChRs). The first venom acylpolyamines ever discovered (argiopines, Joro and Nephila toxins, and philanthotoxins) have provided templates for the design and synthesis of numerous analogs. Thus far, analogs with high potency exert their effect at nanomolar concentrations, with high se-lectivity toward their ionotropic and ligand receptors. These potent and selective acylpolyamine analogs can serve biomedical purposes and pest control management. The structural modification of acylpolyamine with photolabile and fluorescent groups converted these venom toxins into use-ful molecular probes to discriminate iGluRs and nAchRs in cell populations. In various cases, the linear polyamines, like spermine and spermidine, constituting venom acyl polyamine backbones, have served as cargoes to deliver active molecules via a polyamine uptake system on diseased cells for targeted therapy. In this review, we examined examples of biogenic amines that play an essential role in neural homeostasis and cell signaling, contributing to human health and disease outcomes, which can be present in the venom of arachnids and hymenopterans. With an empha-sis on the spider and wasp venom acylpolyamines, we focused on the origin, structure, derivatiza-tion, and biomedical and biotechnological application of these pharmacologically attractive, chemically modular venom components.
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Insecticidas , Poliaminas , Venenos de Araña , Avispas , Animales , Poliaminas/química , Venenos de Araña/química , Venenos de Araña/toxicidad , Insecticidas/farmacología , Insecticidas/química , Insecticidas/toxicidad , Humanos , ArañasRESUMEN
α-Latrotoxin (α-LTX) was found to form two-dimensional (2D) monolayer arrays in solution at relatively low concentrations (0.1 mg/mL), with the toxin tetramer constituting a unit cell. The crystals were imaged using cryogenic electron microscopy (cryoEM), and image analysis yielded a ~12 Å projection map. At this resolution, no major conformational changes between the crystalline and solution states of α-LTX tetramers were observed. Electrophysiological studies showed that, under the conditions of crystallization, α-LTX simultaneously formed multiple channels in biological membranes that displayed coordinated gating. Two types of channels with conductance levels of 120 and 208 pS were identified. Furthermore, we observed two distinct tetramer conformations of tetramers both when observed as monodisperse single particles and within the 2D crystals, with pore diameters of 11 and 13.5 Å, suggestive of a flickering pore in the middle of the tetramer, which may correspond to the two states of toxin channels with different conductance levels. We discuss the structural changes that occur in α-LTX tetramers in solution and propose a mechanism of α-LTX insertion into the membrane. The propensity of α-LTX tetramers to form 2D crystals may explain many features of α-LTX toxicology and suggest that other pore-forming toxins may also form arrays of channels to exert maximal toxic effect.
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Microscopía por Crioelectrón , Animales , Venenos de Araña/química , Venenos de Araña/toxicidad , Membrana Celular/química , Multimerización de Proteína , CristalizaciónRESUMEN
Animal venoms are a promising source of potential bioinsecticides. To find hits with pronounced oral insect toxicity, we screened 82 venoms using Achroia grisella (Lepidoptera) and Tenebrio molitor (Coleoptera) larvae, and adult Drosophila melanogaster (Diptera). We also injected the most potent venoms in adult D. melanogaster to compare their efficiency in different routes of administration. 18 venoms from spiders and snakes show high oral toxicity and can be further exploited to isolate new insecticides.
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Insecticidas , Venenos de Araña , Animales , Ponzoñas , Drosophila melanogaster , Venenos de Araña/toxicidad , Insectos , Insecticidas/toxicidad , LarvaRESUMEN
Diabetic neuropathic pain is one of the complications that affect a wide variety of the diabetic population and is often difficult to treat. Only a small number of patients experience pain relief, which usually comes with onerous side effects and low levels of satisfaction. The search for new analgesic drugs is necessary, given the limitations that current drugs present. Combining drugs to treat neuropathic pain has been attracting interest to improve their efficacy compared to single-drug monotherapies while also reducing dose sizes to minimize side effects. The aim of our study was to verify the antinociceptive effect of a synthetic peptide, PnPP-15, alone and combined with pregabalin, in male Swiss diabetic mice using the von Frey method. PnPP-15 is a synthetic peptide derived from PnPP19, a peptide representing a discontinuous epitope of the primary structure of the toxin PnTx2-6 from the venom of the spider Phoneutria nigriventer. The antinociceptive activity of both compounds was dose-dependent and showed synergism, which was verified by isobolographic analysis. Treatment with PnPP-15 did not cause spontaneous or forced motor changes and did not cause any damage or signs of toxicity in the analyzed organs (pancreas, lung, heart, kidney, brain, or liver). In conclusion, PnPP-15 is a great candidate for an analgesic drug against neuropathic pain caused by diabetes and exerts a synergistic effect when combined with pregabalin, allowing for even more efficient treatment.
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Diabetes Mellitus Experimental , Neuralgia , Venenos de Araña , Humanos , Ratas , Ratones , Masculino , Animales , Pregabalina/farmacología , Pregabalina/uso terapéutico , Ratas Wistar , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Venenos de Araña/uso terapéutico , Venenos de Araña/toxicidad , Venenos de Araña/química , Péptidos/farmacología , Péptidos/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Neuralgia/tratamiento farmacológicoRESUMEN
Sphingomyelinase D (SMase D), the main toxic component of Loxosceles venom, has a well-documented role on dermonecrotic lesion triggered by envenomation with these species; however, the intracellular mechanisms involved in this event are still poorly known. Through differential transcriptomics of human keratinocytes treated with L. laeta or L. intermedia SMases D, we identified 323 DEGs, common to both treatments, as well as upregulation of molecules involved in the IL-1 and ErbB signaling. Since these pathways are related to inflammation and wound healing, respectively, we investigated the relative expression of some molecules related to these pathways by RT-qPCR and observed different expression profiles over time. Although, after 24 h of treatment, both SMases D induced similar modulation of these pathways in keratinocytes, L. intermedia SMase D induced earlier modulation compared to L. laeta SMase D treatment. Positive expression correlations of the molecules involved in the IL-1 signaling were also observed after SMases D treatment, confirming their inflammatory action. In addition, we detected higher relative expression of the inhibitor of the ErbB signaling pathway, ERRFI1, and positive correlations between this molecule and pro-inflammatory mediators after SMases D treatment. Thus, herein, we describe the cell pathways related to the exacerbation of inflammation and to the failure of the wound healing, highlighting the contribution of the IL-1 signaling pathway and the ERRFI1 for the development of cutaneous loxoscelism.
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Esfingomielina Fosfodiesterasa , Venenos de Araña , Animales , Humanos , Inflamación , Interleucina-1/metabolismo , Hidrolasas Diéster Fosfóricas/toxicidad , Transducción de Señal , Esfingomielina Fosfodiesterasa/metabolismo , Arañas/química , Arañas/metabolismo , Venenos de Araña/toxicidad , Picaduras de Arañas/patología , Receptores ErbB/metabolismoRESUMEN
BACKGROUND: Excessive use of chemical insecticides raises concerns about insecticide resistance, urging the development of novel insecticides. Peptide neurotoxins from spider venom are an incredibly rich source of ion channel modulators with potent insecticidal activity. A neurotoxin U1-Atypitoxin-Cs1a from the spider Calommata signata was annotated previously. It was of interest to investigate its insecticidal activity and potential molecular targets. RESULTS: Cs1a was heterologously expressed, purified and pharmacologically characterized here. The recombinant neurotoxin inhibited high-voltage-activated calcium channel currents with an median inhibitory concentration (IC50 ) value of 0.182 ± 0.026 µm on cockroach DUM neurons and thus was designated as ω-Atypitoxin-Cs1a. The recombinant Cs1a was toxic to three insect pests of agricultural importance, Nilaparvata lugens, Spodoptera frugiperda and Plutella xylostella with median lethal concentration (LD50 ) values of 0.121, 0.172 and 0.356 nmol g-1 , respectively, at 24 h postinjection. Cs1a was equivalently toxic to both insecticide-susceptible and -resistant insects. Cs1a exhibited low toxicity to Danio rerio with an LD50 of 2.316 nmol g-1 . CONCLUSION: Our results suggest that ω-Atypitoxin-Cs1a is a potent CaV channel inhibitor and an attractive candidate reagent for pest control and resistance management. © 2023 Society of Chemical Industry.
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Cucarachas , Insecticidas , Venenos de Araña , Animales , Neurotoxinas/toxicidad , Insecticidas/farmacología , Insecticidas/química , Canales de Calcio/farmacología , Péptidos , Venenos de Araña/toxicidad , Venenos de Araña/químicaRESUMEN
Effective control of diseases transmitted by Aedes aegypti is primarily achieved through vector control by chemical insecticides. However, the emergence of insecticide resistance in A. aegypti undermines current control efforts. Arachnid venoms are rich in toxins with activity against dipteran insects and we therefore employed a panel of 41 spider and 9 scorpion venoms to screen for mosquitocidal toxins. Using an assay-guided fractionation approach, we isolated two peptides from the venom of the tarantula Lasiodora klugi with activity against adult A. aegypti. The isolated peptides were named U-TRTX-Lk1a and U-TRTX-Lk2a and comprised 41 and 49 residues with monoisotopic masses of 4687.02 Da and 5718.88 Da, respectively. U-TRTX-Lk1a exhibited an LD50 of 38.3 pmol/g when injected into A. aegypti and its modeled structure conformed to the inhibitor cystine knot motif. U-TRTX-Lk2a has an LD50 of 45.4 pmol/g against adult A. aegypti and its predicted structure conforms to the disulfide-directed ß-hairpin motif. These spider-venom peptides represent potential leads for the development of novel control agents for A. aegypti.
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Venenos de Araña , Ponzoñas , Animales , Ponzoñas/farmacología , Brasil , Mosquitos Vectores , Péptidos/farmacología , Insectos , Venenos de Araña/toxicidad , Venenos de Araña/químicaRESUMEN
The wandering spider, Phoneutria depilata, is one of Colombia's most active nocturnal arthropod predators of vertebrates and invertebrates. Its venom has been a relevant subject of study in the last two decades. However, the scarcity of transcriptomic data for the species limits our knowledge of the distinct components present in its venom for linking the mainly neurotoxic effects of the spider venom to a particular molecular target. The transcriptome of the P. depilata venom gland was analyzed to understand the effect of different diets or sex and the impact of these variables on the composition of the venom. We sequenced venom glands obtained from ten males and ten females from three diet treatments: (i) invertebrate: Tenebrio molitor, (ii) vertebrate: Hemidactylus frenatus, and (iii) mixed (T. molitor + H. frenatus). Of 17,354 assembled transcripts from all samples, 65 transcripts relating to venom production differed between males and females. Among them, 36 were classified as neurotoxins, 14 as serine endopeptidases, 11 as other proteins related to venom production, three as metalloprotease toxins, and one as a venom potentiator. There were no differences in transcripts across the analyzed diets, but when considering the effect of diets on differences between the sexes, 59 transcripts were differentially expressed. Our findings provide essential information on toxins differentially expressed that can be related to sex and the plasticity of the diet of P. depilata and thus can be used as a reference for venomics of other wandering spider species.
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Venenos de Araña , Arañas , Toxinas Biológicas , Animales , Femenino , Masculino , Perfilación de la Expresión Génica , Vertebrados , Transcriptoma , Arañas/genética , Arañas/metabolismo , Ponzoñas , Venenos de Araña/genética , Venenos de Araña/toxicidad , Venenos de Araña/metabolismoRESUMEN
Spider venoms are composed, among other substances, of peptide toxins whose selectivity for certain physiological targets has made them powerful tools for applications such as bioinsecticides, analgesics, antiarrhythmics, antibacterials, antifungals and antimalarials, among others. Bioinsecticides are an environmentally friendly alternative to conventional agrochemicals. In this paper, the primary structure of an insecticidal peptide was obtained from the venom gland transcriptome of the ctenid spider Phoneutria depilata (Transcript ID PhdNtxNav24). The peptide contains 53 amino acids, including 10 Cys residues that form 5 disulfide bonds. Using the amino acid sequence of such peptide, a synthetic gene was constructed de novo by overlapping PCRs and cloned into an expression vector. A recombinant peptide, named delta-ctenitoxin (rCtx-4), was obtained. It was expressed, folded, purified and validated using mass spectrometry (7994.61 Da). The insecticidal activity of rCtx-4 was demonstrated through intrathoracic injection in crickets (LD50 1.2 µg/g insect) and it was not toxic to mice. rCtx-4 is a potential bioinsecticide that could have a broad spectrum of applications in agriculture.
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Insecticidas , Venenos de Araña , Arañas , Ratones , Animales , Insecticidas/farmacología , Insecticidas/química , Transcriptoma , Colombia , Péptidos/farmacología , Péptidos/toxicidad , Venenos de Araña/genética , Venenos de Araña/toxicidad , Venenos de Araña/química , Arañas/genéticaRESUMEN
Established dogma concerning the action of insecticidal arthropod-derived peptides (e.g., scorpion toxins), was that they acted on the peripheral nervous system and were excluded from the central nervous system (CNS) by barrier systems. Initial evidence for a CNS-directed toxicological effect following parenteral administration was for a novel peptide from the Hobo spider, Tegeneria agrestis. This toxin was inactive on peripheral sensory and motor nerves, but had a potent excitatory effect on the CNS of larval Musca domestica. Recently, a commercialized formulation of GS-omega/kappa-Hxtx-Hv1a (HXTX), derived from the venom of the Australian blue mountain funnel web spider (Hadronyche versuta) was introduced for use in agriculture by Vestaron Corp. Its primary mode of action was found to be central neuroexcitation via positive allosteric modulation of nicotinic acetylcholine receptors (nAchR) of cockroach neurons. In the present study, this peptide showed hyperexcitation followed by a decrease in firing of the Drosophila melanogaster larval CNS that was prevented by co-exposure to 100 nM α-bungarotoxin (α-BGTX), a classical nAchR noncompetitive antagonist. This effect was mirrored in isobologram analysis, which showed clear antagonism between the two toxins when injected into adult houseflies. Interestingly, U1-agatoxin-Ta1b-QA derived from Tegeneria agrestis (VST-7304) had a similar biphasic action, but showed increased nerve discharge when co-exposed with 100 nM α-BGTX, and had additive effects when injected together with α-BGTX in isobologram analyses. Binary mixtures of HXTX or VST-7304 with 30 nM nicotine showed clear evidence of synergized nerve block, which was also observed for mixtures of HXTX and VST-7304. Taken together, these data suggest that HXTX and VST-7304 have somewhat different and complementary modes of action.
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Proteínas de Drosophila , Venenos de Araña , Animales , Venenos de Araña/toxicidad , Drosophila melanogaster , Australia , Péptidos/farmacologíaRESUMEN
Tarantulas are commonly kept as pets and bites from some species can cause severe symptoms. Here we describe a case of a patient with transient atrial fibrillation (afib) and painful muscle cramps requiring hospitalization for pain management after being bitten by a Poecilotheria tigrinawesseli (Wessel's Tiger Ornamental) spider. He was discharged with a cardiac event monitor and outpatient cardiology follow-up. The event monitor documented transient afib which decreased in frequency then resolved halfway through the three-week monitoring period. In conclusion, tarantula envenomation is usually mild with local pain and edema most reported. However, bites by some species, such as P. tigrinawesseli may have local and more systemic, long-lasting effects.
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Artrópodos , Fibrilación Atrial , Mordeduras y Picaduras , Picaduras de Arañas , Venenos de Araña , Arañas , Tigres , Masculino , Animales , Picaduras de Arañas/complicaciones , Mordeduras y Picaduras/complicaciones , Venenos de Araña/toxicidadRESUMEN
The brown recluse spider (Loxosceles reclusa) is endemic to the South, West and Central Midwestern United States, and envenomation from this spider can cause cutaneous and/or systemic symptoms. We present a case of systemic loxocelism in an adolescent male resulting in three emergency department visits and two hospitalizations for a rare case of delayed hemolysis 6 days after envenomation. A 19-year-old male presented to the emergency department twice within two days after envenomation with worsening pain, subjective fever, chills, nausea and vomiting. He required a two-day hospitalization for rhabdomyolysis and acute kidney injury. The patient was discharged with improving symptoms and laboratory results on day four before returning again on day seven with worsening symptoms. He was diagnosed with hemolytic anemia on day seven and was subsequently hospitalized for six days. This case of systemic loxoscelism manifested hemolysis six days after envenomation, following an improvement in symptoms and laboratory studies. This case highlights the need for continuous monitoring and/or follow-up in cases of systemic loxocelism.
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Anemia Hemolítica , Picaduras de Arañas , Venenos de Araña , Animales , Masculino , Hemólisis , Araña Reclusa Parda , Picaduras de Arañas/complicaciones , Picaduras de Arañas/diagnóstico , Venenos de Araña/toxicidad , Anemia Hemolítica/inducido químicamenteRESUMEN
Prey-specialised spiders are adapted to capture specific prey items, including dangerous prey. The venoms of specialists are often prey-specific and less complex than those of generalists, but their venom composition has not been studied in detail. Here, we investigated the venom of the prey-specialised white-tailed spiders (Lamponidae: Lampona), which utilise specialised morphological and behavioural adaptations to capture spider prey. We analysed the venom composition using proteo-transcriptomics and taxon-specific toxicity using venom bioassays. Our analysis identified 208 putative toxin sequences, comprising 103 peptides < 10 kDa and 105 proteins > 10 kDa. Most peptides belonged to one of two families characterised by scaffolds containing eight or ten cysteine residues. Toxin-like proteins showed similarity to galectins, leucine-rich repeat proteins, trypsins and neprilysins. The venom of Lampona was shown to be more potent against the preferred spider prey than against alternative cricket prey. In contrast, the venom of a related generalist was similarly potent against both prey types. These data provide insights into the molecular adaptations of venoms produced by prey-specialised spiders.
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Venenos de Araña , Arañas , Animales , Arañas/química , Venenos de Araña/toxicidad , Venenos de Araña/química , Conducta Predatoria , Adaptación Fisiológica , Péptidos/toxicidadRESUMEN
Australian funnel-web spiders are amongst the most dangerous venomous animals. Their venoms induce potentially deadly symptoms, including hyper- and hypotension, tachycardia, bradycardia and pulmonary oedema. Human envenomation is more frequent with the ground-dwelling species, including the infamous Sydney funnel-web spider (Atrax robustus); although, only two tree-dwelling species induce more severe envenomation. To unravel the mechanisms that lead to this stark difference in clinical outcomes, we investigated the venom transcriptome and proteome of arboreal Hadronyche cerberea and H. formidabilis. Overall, Hadronyche venoms comprised 44 toxin superfamilies, with 12 being exclusive to tree-dwellers. Surprisingly, the major venom components were neprilysins and uncharacterized peptides, in addition to the well-known ω- and δ-hexatoxins and double-knot peptides. The insecticidal effects of Hadronyche venom on sheep blowflies were more potent than Atrax venom, and the venom of both tree- and ground-dwelling species potently modulated human voltage-gated sodium channels, particularly NaV1.2. Only the venom of tree-dwellers exhibited potent modulation of voltage-gated calcium channels. H. formidabilis appeared to be under less diversifying selection pressure compared to the newly adapted tree-dweller, H. cerberea. Thus, this study contributes to unravelling the fascinating molecular and pharmacological basis for the severe envenomation caused by the Australian tree-dwelling funnel-web spiders.
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Venenos de Araña , Arañas , Animales , Humanos , Venenos de Araña/toxicidad , Venenos de Araña/química , Árboles , Australia , PéptidosRESUMEN
Diagnostic tests for brown spider accidents are unavailable and impact treatment decisions, increasing costs and patient risks. In this work, we used for the first time a fast, simple, and visual method based on the loop-mediated isothermal amplification assay (LAMP) to detect Loxosceles envenomation. Using the DNA from L. similis legs, we observed a high sensitivity using this test since as low as 0.32 pg of DNA could be detected. This pH-dependent colorimetric assay was 64 times more sensitive than PCR to detect spider DNA. The test was specific for Loxosceles once no cross-reaction was observed when testing DNA from different agents that cause similar dermonecrotic injuries. The test allowed the detection of Loxosceles intermedia DNA from hair, serum, and exudate samples obtained from experimentally-envenomed rabbit within 72 h. The method sensitivity varied according to the sample and the collection time, reaching 100% sensitivity in serum and hair, respectively, 1 h and 24 h after the experimental envenomation. Due to its ease of execution, speed, sensitivity, and specificity, LAMP presents an excellent potential for identifying Loxosceles spp. Envenomation. This can reduce the burden on the Health System and the morbidity for the patient by implementing the appropriate therapy immediately.In addition, this work opens up the perspective to other venomous animal accident identification using LAMP.
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Venenos de Araña , Arañas , Animales , Colorimetría , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , Hidrolasas Diéster Fosfóricas/genética , Conejos , Sensibilidad y Especificidad , Venenos de Araña/genética , Venenos de Araña/toxicidad , Arañas/genéticaRESUMEN
Five funnel-web spiders in the genus Macrothele are widely distributed to Taiwan. We herein reported the severe case of a woman bitten by a male Macrothele gigas who present with autonomic (i.e., profuse sweating and piloerection), cardiovascular (hypertension and tachycardia), and neurologic effects (perioral numbness) in addition to local tissue swelling and regional limb pain. Morphine and ampicillin/sulbactam were administered. Her cardiovascular, neurologic, and local symptoms gradually improved, and thus was discharged 24 h post-bite. However, persistent diaphoresis and piloerection lasted for at least 3 days, and pre-renal azotemia was suspected. Due to the risk of severity and death reported for the Australian funnel web spider bites, we suggest patients bitten by an Asian funnel-web spider be carefully monitored and resuscitation performed as indicated.
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Picaduras de Arañas , Venenos de Araña , Arañas , Animales , Femenino , Humanos , Masculino , Dolor , Picaduras de Arañas/diagnóstico , Venenos de Araña/toxicidad , TaiwánRESUMEN
We used α-Latrotoxin (α-LTx), the main neurotoxic component of the black widow spider venom, which causes degeneration of the neuromuscular junction (NMJ) followed by a rapid and complete regeneration, as a molecular tool to identify by RNA transcriptomics factors contributing to the structural and functional recovery of the NMJ. We found that Urocortin 2 (UCN2), a neuropeptide involved in the stress response, is rapidly expressed at the NMJ after acute damage and that inhibition of CRHR2, the specific receptor of UCN2, delays neuromuscular transmission rescue. Experiments in neuronal cultures show that CRHR2 localises at the axonal tips of growing spinal motor neurons and that its expression inversely correlates with synaptic maturation. Moreover, exogenous UCN2 enhances the growth of axonal sprouts in cultured neurons in a CRHR2-dependent manner, pointing to a role of the UCN2-CRHR2 axis in the regulation of axonal growth and synaptogenesis. Consistently, exogenous administration of UCN2 strongly accelerates the regrowth of motor axon terminals degenerated by α-LTx, thereby contributing to the functional recovery of neuromuscular transmission after damage. Taken together, our results posit a novel role for UCN2 and CRHR2 as a signalling axis involved in NMJ regeneration.
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Axones/fisiología , Neuronas Motoras/citología , Regeneración Nerviosa , Enfermedades de la Unión Neuromuscular/prevención & control , Unión Neuromuscular/patología , Venenos de Araña/toxicidad , Urocortinas/metabolismo , Animales , Femenino , Ratones , Ratones Endogámicos C57BL , Unión Neuromuscular/efectos de los fármacos , Enfermedades de la Unión Neuromuscular/inducido químicamente , Enfermedades de la Unión Neuromuscular/metabolismo , Enfermedades de la Unión Neuromuscular/patología , Terminales Presinápticos , Ratas , Ratas Sprague-Dawley , Urocortinas/genéticaRESUMEN
Loxoscelism occurs when the dermonecrotic venom produced by spiders of the genus Loxosceles, known as "violin spiders," enters a person's organism through their bite. In Mexico there is an underreporting of loxoscelism cases due to the absence of laboratory tests for its diagnosis and the complexity of the clinical picture. The aim of this paper is to describe a case of cutaneous loxoscelism caused by the bite of Loxosceles yucatana in a resident of Yucatan, Mexico. Cutaneous loxoscelism is the most frequent and less severe type. This case was diagnosed by means of the symptomatology registered in the medical records, the initial lesion, and the identification of L. yucatana spiders. This study represents the first description of a case of cutaneous loxoscelism with favorable outcome in Yucatan.
El loxoscelismo es ocasionado cuando el veneno dermonecrótico producido por las arañas del género Loxosceles, conocidas como «arañas violinistas¼, ingresa al organismo de una persona a través de su mordida. En México ocurre un subregistro de los casos de loxoscelismo por la ausencia de pruebas de laboratorio para su diagnóstico y la dificultad del cuadro clínico. El objetivo de este trabajo es describir un caso de loxoscelismo cutáneo ocasionado por mordedura de Loxosceles yucatana en un residente de Yucatán, México. El loxoscelismo cutáneo es el tipo más frecuente y menos severo. El presente caso se diagnosticó por medio de la sintomatología registrada en la historia clínica, la lesión inicial y la identificación de arañas L. yucatana. Este trabajo representa la primera descripción de un caso de loxoscelismo cutáneo con resolución favorable en Yucatán.
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Picaduras de Arañas , Venenos de Araña , Arañas , Animales , Picaduras de Arañas/diagnóstico , Picaduras de Arañas/patología , Venenos de Araña/toxicidad , Araña Reclusa Parda , MéxicoRESUMEN
Bites of Loxosceles spiders can lead to a set of clinical manifestations called loxoscelism, and are considered a public health problem in many regions. The signs and symptoms of loxoscelism are divided into cutaneous and systemic forms. The former is more frequent and includes signs of envenoming at the bite site or neighboring regions. Systemic loxoscelism, although much less frequent, is associated with complications, and can even lead to death. It may include intravascular hemolysis, acute renal failure, and thrombocytopenia. Loxosceles venoms are enriched with phospholipases D (PLDs), which are a family of isoforms found at intra-species and inter-species levels. Under experimental conditions, these enzymes reproduce the main clinical signs of loxoscelism, including an exacerbated inflammatory response at the bite site and dermonecrosis, as well as thrombocytopenia, intravascular hemolysis, and acute renal failure. The role of PLDs in cutaneous loxoscelism was described over forty years ago, when studies identified and purified toxins featured as sphingomyelinase D. More recently, the production of recombinant PLDs and discoveries about their structure and mechanism has enabled a deeper characterization of these enzymes. In this review, we describe these biochemical and functional features of Loxosceles PLDs that determine their involvement in systemic loxoscelism.