Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 854
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
J Biol Chem ; 299(3): 102946, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36707054

RESUMO

Voltage-gated sodium and calcium channels are distinct, evolutionarily related ion channels that achieve remarkable ion selectivity despite sharing an overall similar structure. Classical studies have shown that ion selectivity is determined by specific binding of ions to the channel pore, enabled by signature amino acid sequences within the selectivity filter (SF). By studying ancestral channels in the pond snail (Lymnaea stagnalis), Guan et al. showed in a recent JBC article that this well-established mechanism can be tuned by alternative splicing, allowing a single CaV3 gene to encode both a Ca2+-permeable and an Na+-permeable channel depending on the cellular context. These findings shed light on mechanisms that tune ion selectivity in physiology and on the evolutionary basis of ion selectivity.


Assuntos
Processamento Alternativo , Canais de Cálcio , Canais de Sódio Disparados por Voltagem , Animais , Sequência de Aminoácidos , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Íons/metabolismo , Caramujos/metabolismo , Canais de Sódio Disparados por Voltagem/metabolismo
2.
Biometals ; 37(3): 671-696, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38416244

RESUMO

This is a critical review of what we know so far about the evolution of metallothioneins (MTs) in Gastropoda (snails, whelks, limpets and slugs), an important class of molluscs with over 90,000 known species. Particular attention will be paid to the evolution of snail MTs in relation to the role of some metallic trace elements (cadmium, zinc and copper) and their interaction with MTs, also compared to MTs from other animal phyla. The article also highlights the important distinction, yet close relationship, between the structural and metal-selective binding properties of gastropod MTs and their physiological functionality in the living organism. It appears that in the course of the evolution of Gastropoda, the trace metal cadmium (Cd) must have played an essential role in the development of Cd-selective MT variants. It is shown how the structures and Cd-selective binding properties in the basal gastropod clades have evolved by testing and optimizing different combinations of ancestral and novel MT domains, and how some of these domains have become established in modern and recent gastropod clades. In this context, the question of how adaptation to new habitats and lifestyles has affected the original MT traits in different gastropod lineages will also be addressed. The 3D structures and their metal binding preferences will be highlighted exemplarily in MTs of modern littorinid and helicid snails. Finally, the importance of the different metal requirements and pathways in snail tissues and cells for the shaping and functionality of the respective MT isoforms will be shown.


Assuntos
Evolução Molecular , Metalotioneína , Caramujos , Metalotioneína/metabolismo , Metalotioneína/química , Metalotioneína/genética , Animais , Caramujos/metabolismo , Caramujos/química , Cádmio/metabolismo , Cádmio/química , Zinco/metabolismo , Zinco/química , Metais/metabolismo , Metais/química
3.
Parasitol Res ; 123(7): 257, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940835

RESUMO

As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.


Assuntos
Glucose , Moluscocidas , Caramujos , Animais , Moluscocidas/farmacologia , Caramujos/efeitos dos fármacos , Caramujos/metabolismo , Caramujos/parasitologia , Glucose/metabolismo , Água Doce
4.
Int Microbiol ; 26(4): 961-972, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37020067

RESUMO

Phytases are specialized enzymes meant for phytic acid degradation. They possess ability to prevent phytic acid indigestion, including its attendant environmental pollution. This study was aimed at investigating biochemical properties of purified phytase of B. cereus isolated from Achatina fulica. Phytase produced from Bacillus cereus that exhibited optimal phytate degrading-ability of all the bacteria isolated was purified in a three-step purification. The biochemical properties of the purified enzyme were also determined. The phytase homogeny of approximately 45 kDa exhibited 12.8-purification fold and 1.6% yield with optima phytate degrading efficiency and maximum stability at pH 7 and 50 °C. Remaining activity of 52 and 47% obtained between 60 and 70 °C after 2 h further established thermostability of the purified phytase. Mg2+ and Zn2+ enhanced phytate hydrolysis by the enzyme, while Na+ showed mild inhibition but Hg2+ severely inhibited the enzymatic activity. Km and Vmax were estimated to be 0.11 mM and 55.6 µmol/min/mL, displaying enzyme-high substrate affinity and catalytic efficiency, respectively. Phytase purified from Bacillus cereus, isolated from African giant snails, has shown excellent characteristics suitable for phytic acid hydrolysis and could be employed in industrial and biotechnological applications.


Assuntos
6-Fitase , Bacillus cereus , Animais , Bacillus cereus/metabolismo , 6-Fitase/química , 6-Fitase/metabolismo , Ácido Fítico/química , Ácido Fítico/metabolismo , Caramujos/metabolismo , Trato Gastrointestinal , Concentração de Íons de Hidrogênio
5.
Int J Mol Sci ; 24(23)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38069390

RESUMO

Benzodiazepines, psychotropic drugs, are ubiquitous in the aquatic environment due to over-consumption and inefficient removal by sewage treatment plants. Bioaccumulation with consequent behavioral and physiological effects has been reported in many aquatic species. However, the responses are species-specific and still poorly understood. To improve the knowledge, we exposed the freshwater snail Planorbarius corneus to 1, 5, or 10 µg/L of delorazepam, the most widely consumed benzodiazepine in Italy. Conventional behavioral tests were used to assess the effects on locomotor and feeding behavior. Histological and biochemical analyses were also performed to detect possible changes in the structure and composition of the foot mucus and glands. The results show a paradoxical response with reduced feeding activity and locomotor hyperactivity. Pedal mucus was altered in texture but not in composition, becoming particularly rich in fibrous collagen-like material, and a significant change in the protein composition was highlighted in the foot. In conclusion, exposure to delorazepam induces disinhibited behavior in Planorbarius corneus, potentially increasing the risk of predation, and an increase in mucus protein production, which, together with reduced feeding activity, would severely compromise energy resources.


Assuntos
Benzodiazepinas , Caramujos , Animais , Caramujos/metabolismo , Benzodiazepinas/farmacologia , Benzodiazepinas/metabolismo , Água Doce
6.
Environ Geochem Health ; 45(5): 2591-2610, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36063241

RESUMO

Information on the oxidative stress physiology parameters (OSPP) in general and as a function of the fluctuation of Mg, Ca and organic carbon present in soil and aquatic physico-chemical factors such as pH, temperature and salinity in particular are scanty in the amphibious snail Pila globosa. A spatio-temporal analysis of redox metabolism (as OSPP) followed by discriminant function analysis of the obtained data were performed in P. globosa sampled from the east-coasts of Odisha state, India (mostly along the Bay of Bengal) for environmental health assessment purposes. Results revealed that the OSPP are susceptible to seasonal synergistic variation of soil and physico-chemical factors. Overall, lipid peroxidation, total antioxidant capacity, activities of catalase, glutathione reductase had positive correlation whereas ascorbic acid, the reduced glutathione and the activity of superoxide dismutase had non-significant correlation with the soil Mg, Ca, organic carbon, and pH, temperature and salinity of water. In the summer season, the snails had a marked 51.83% and 26.41% higher lipid peroxidation level and total antioxidative activity as compared to the other seasons. Spatial variation of OSPP indicates that snails residing away from the Bay of Bengal coast had at least 4.4% lower antioxidant level in winter and 30% higher lipid peroxide levels in summer as compared to the rest of the sampling sites. Results on OSPP in P. globosa may be useful for monitoring the ecotoxic effects of environment using molluscs in general and P. globosa in particular.


Assuntos
Antioxidantes , Carbono , Animais , Antioxidantes/metabolismo , Carbono/metabolismo , Estresse Oxidativo , Caramujos/metabolismo , Ácido Ascórbico/metabolismo
7.
Dev Biol ; 470: 1-9, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33191200

RESUMO

Caudal homeobox genes are found across animals, typically linked to two other homeobox genes in what has been called the ParaHox cluster. These genes have been proposed to pattern the anterior-posterior axis of the endoderm ancestrally, but the expression of Caudal in extant groups is varied and often occurs in other germ layers. Here we examine the role of Caudal in the embryo of the mollusc Tritia (Ilyanassa) obsoleta. ToCaudal expression is initially broad, then becomes progressively restricted and is finally only in the developing hindgut (a.k.a. intestine). Knockdown of ToCaudal using morpholino oligonucleotides specifically blocks hindgut development, indicating that despite its initially broad expression, the functional role of ToCaudal is in hindgut patterning. This is the first functional characterization of Caudal in an animal with spiralian development, which is an ancient mode of embryogenesis that arose early in bilaterian animal evolution. These results are consistent with the hypothesis that the ancestral role of the ParaHox genes was anterior-posterior patterning of the endoderm.


Assuntos
Padronização Corporal/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes Homeobox , Caramujos/embriologia , Caramujos/genética , Animais , Sistema Digestório/embriologia , Embrião não Mamífero/metabolismo , Técnicas de Silenciamento de Genes , Camadas Germinativas/embriologia , Camadas Germinativas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Família Multigênica , Filogenia , Caramujos/metabolismo
8.
Dev Biol ; 478: 122-132, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34224682

RESUMO

Sexual systems are surprisingly diverse, considering the ubiquity of sexual reproduction. Sequential hermaphroditism, the ability of an individual to change sex, has emerged multiple times independently across the animal kingdom. In molluscs, repeated shifts between ancestrally separate sexes and hermaphroditism are generally found at the level of family and above, suggesting recruitment of deeply conserved mechanisms. Despite this, molecular mechanisms of sexual development are poorly known. In molluscs with separate sexes, endocrine disrupting toxins bind the retinoid X receptor (RXR), activating ectopic male development in females, suggesting the retinoid pathway as a candidate controlling sexual transitions in sequential hermaphrodites. We therefore tested the role of retinoic acid signaling in sequentially hermaphroditic Crepidula snails, which develop first into males, then change sex, maturing into females. We show that retinoid agonists induce precocious penis growth in juveniles and superimposition of male development in females. Combining RXR antagonists with retinoid agonists significantly reduces penis length in induced juveniles, while similar treatments using retinoic acid receptor (RAR) antagonists increase penis length. Transcripts of both receptors are expressed in the induced penis. Our findings therefore show that retinoid signaling can initiate molluscan male genital development, and regulate penis length. Further, we show that retinoids induce ectopic male development in multiple Crepidula species. Species-specific influence of conspecific induction of sexual transitions correlates with responsiveness to retinoids. We propose that retinoid signaling plays a conserved role in molluscan male development, and that shifts in the timing of retinoid signaling may have been important for the origins of sequential hermaphroditism within molluscs.


Assuntos
Organismos Hermafroditas/crescimento & desenvolvimento , Retinoides/metabolismo , Caramujos/crescimento & desenvolvimento , Caramujos/metabolismo , Animais , Família 26 do Citocromo P450/genética , Feminino , Organismos Hermafroditas/genética , Organismos Hermafroditas/metabolismo , Masculino , Pênis/crescimento & desenvolvimento , Pênis/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do Ácido Retinoico/agonistas , Receptores do Ácido Retinoico/antagonistas & inibidores , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Receptores X de Retinoides/agonistas , Receptores X de Retinoides/genética , Receptores X de Retinoides/metabolismo , Transdução de Sinais , Caramujos/anatomia & histologia , Caramujos/genética , Especificidade da Espécie , Tretinoína/metabolismo , Compostos de Trialquitina/farmacologia
9.
Development ; 146(9)2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088796

RESUMO

The establishment of left-right body asymmetry is a key biological process that is tightly regulated genetically. In the first application of CRISPR/Cas9 to a mollusc, we show decisively that the actin-related diaphanous gene Lsdia1 is the single maternal gene that determines the shell coiling direction of the freshwater snail Lymnaea stagnalis Biallelic frameshift mutations of the gene produced sinistrally coiled offspring generation after generation, in the otherwise totally dextral genetic background. This is the gene sought for over a century. We also show that the gene sets the chirality at the one-cell stage, the earliest observed symmetry-breaking event linked directly to body handedness in the animal kingdom. The early intracellular chirality is superseded by the inter-cellular chirality during the 3rd cleavage, leading to asymmetric nodal and Pitx expression, and then to organismal body handedness. Thus, our findings have important implications for chiromorphogenesis in invertebrates as well as vertebrates, including humans, and for the evolution of snail chirality. This article has an associated 'The people behind the papers' interview.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Moluscos/genética , Animais , Padronização Corporal/genética , Padronização Corporal/fisiologia , Forminas/genética , Forminas/metabolismo , Lymnaea/genética , Lymnaea/metabolismo , Moluscos/metabolismo , Caramujos/genética , Caramujos/metabolismo
10.
Chembiochem ; 23(13): e202200074, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35543120

RESUMO

Aldolases are enzymes that reversibly catalyze the cleavage of carbon-carbon bonds. Here we describe a recombinant sialic acid aldolase originating from the freshwater snail Biomphalaria glabrata (sNPL), and compare its substrate spectrum with a sialic acid aldolase originating from chicken (chNPL). In contrast to vertebrate animals which can synthesize, degrade, and incorporate sialic acids on glycoconjugate ubiquitously, snails (as all mollusks) cannot synthesize sialic acids endogenously, and therefore the biological function and substrate scope of sNPL ought to differ significantly from vertebrate sialic aldolases such as chNPL. sNPL was active towards a series of sialic acid derivatives but was in contrast to chNPL unable to catalyze the cleavage of N-acetylneuraminic acid into N-acetylmannosamine and pyruvate. Interestingly, chNPL and sNPL showed contrasting C4(R)/(S) diastereoselectivity towards the substrates d-mannose and d-galactose in the presence of pyruvate. In addition, sNPL was able to synthesize a series of 4-hydroxy-2-oxoates using the corresponding aliphatic aldehyde substrates in the presence of pyruvate, which could be not achieved by chNPL.


Assuntos
Aldeído Liases , Aldeídos , Aldeído Liases/metabolismo , Aldeídos/metabolismo , Animais , Carbono , Frutose-Bifosfato Aldolase/metabolismo , Ácido N-Acetilneuramínico , Oxo-Ácido-Liases , Ácido Pirúvico , Ácidos Siálicos , Caramujos/metabolismo , Especificidade por Substrato
11.
Ecotoxicol Environ Saf ; 236: 113514, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35427879

RESUMO

The interactions between hyperaccumulators and their associated herbivores have been mostly investigated in their natural habitats and largely ignored in the phytoremediation practice. Herein, we investigated the herbivory status of Zn/Cd-hyperaccumulating plant Sedum alfredii from both their natural habitats and their applied remediation field, and inspected the adaptive strategies of the herbivores from the perspective of their facilitative gut microbiota. Field investigations showed that snail species Bradybaena ravida was the dominant herbivore feeding on S. alfredii and they can be only found in sites with lower levels of heavy metals compared with the plant natural habitat. Gut microbial community was analyzed using two sequencing methods (16S rRNA and czcA-Zn/Cd resistant gene) to comparatively understand the effect of gut microbes in facilitating snail feeding on the hyperaccumulators. The results revealed significant differences in the diversity and richness between the gut microbiota of the two snail populations, which was more pronounced by the czcA sequencing method. Despite of the compositional differences, their functions seemed to converge into three categories as metal-tolerant and contaminant degraders, gut symbionts, and pathogens. Further function potentials predicted by Tax4Fun based on 16 S sequencing data were in accordance with this categorization as the most abundant metabolic pathways were two-component system and ABC transporter, which was closely related to metal stress adaptation. The prevalence of positive interactions (~80%) indicated by the co-occurrence network analysis based on czcA sequencing data in both groups of gut microbiota further suggested the facilitative effect of these metal-tolerant gut microbes in coping with the high metal diet, which ultimately assist the snails to successfully feed on S. alfredii plants and thrive. This work for the first time provides evidence that the herbivore adaptation to hyperaccumulators were also associated with their gut microbial adaptation to metals.


Assuntos
Microbioma Gastrointestinal , Metais Pesados , Sedum , Poluentes do Solo , Animais , Biodegradação Ambiental , Cádmio/metabolismo , Metais Pesados/análise , Raízes de Plantas/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Sedum/metabolismo , Caramujos/genética , Caramujos/metabolismo , Poluentes do Solo/análise
12.
Int J Mol Sci ; 23(12)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35742982

RESUMO

The identification of compounds and natural ingredients that can counteract tissue stress and dysfunction induced by aging in skin cells is warranted. Here, we investigated the activity of the secretion from the snail Cryptomphalus aspersa (SCA®), an active compound with well-established beneficial effects on skin integrity and aging. To determinate its senescence-regulation mechanisms, we used a model where damage was induced by hydrogen peroxide (H2O2). The results showed that SCA® positively modulated factors involved in cell senescence such as ß-galactosidase and cell morphology, secretory efficiency markers (SIRT1/6 and carboxymethyl-lysine), and metabolic and redox homeostasis (mTOR and ROS). This study demonstrated a novel compound that is activity-modulating, reduces cell senescence, and increases longevity to maintain skin homeostasis and functionality.


Assuntos
Peróxido de Hidrogênio , Pele , Animais , Senescência Celular , Peróxido de Hidrogênio/metabolismo , Sirtuína 1/metabolismo , Pele/metabolismo , Caramujos/metabolismo
13.
Biomarkers ; 26(3): 221-239, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33411589

RESUMO

Background: Bio-indicator systems are vital in terms of monitoring of pollutants around the world. The impact of environmental change can be monitored by employing the responsive behaviour of snails. Heavy metal and organic pollutants affects snail reproduction, mortality, and normal metabolic activities. Various changes like a discontinuity in food intake, growth rate, twitching, and quenching of tentacles, are the biomarkers of the snails for biomonitoring. Different snails can bio-monitor eco-toxicological urban pollution, oil pollutant, terrestrial pollution, pesticide pollutants, mercury contamination, ammonia, chlorinated paraffin in soil, ethanol in water, ocean acidification pollutions. These animals can also make bio-sense about diverse environment spheres, which include the biosphere, lithosphere, anthroposphere, cryosphere, and hydrosphere.Methods: We examined the scientific literature and related articles listed in Pub-med, Google Scholar reporting on biomonitoring potential and biomarkers expression of various snail species and consequently explore the value of snails in the respective field by discussing various outcomes of a number of studies on the pollution biomonitoring and biosensing capabilities.Results: Several terrestrial, freshwater and sea snail species are characterized by the high sense of biomonitoring and biosensing potential. Various biomarkers such as expression of heat shock proteins and metallothioneins in the body are found to be the essential in-vivo biomarkers for pollution biomonitoring.Conclusion: It is observed that snails offer an environment friendly approach for the environmental bio monitoring by expressing their numerous physiological, biochemical, genetical and histological biomarkers in their body. Thus, it proved to be a critical bio monitoring tool and early warning indicators.


Assuntos
Mudança Climática , Biomarcadores Ambientais , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental , Poluentes Ambientais/efeitos adversos , Caramujos/efeitos dos fármacos , Animais , Técnicas Biossensoriais , Proteínas de Choque Térmico/metabolismo , Metalotioneína/metabolismo , Caramujos/metabolismo , Fatores de Tempo
14.
Genomics ; 112(6): 4385-4398, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32730984

RESUMO

The intertidal marine periwinkle, Littorina littorea, have developed various strategies to deal with cyclic exposures to anoxic and/or freezing stresses when out of water at low tide. With promising translational research potential, evolutionarily conserved microRNAs (miRNAs) have recently become a focus of animal stress response studies. Using RNA-seq, the current study explores the conserved hepatopancreas miRNAs in facilitating snail stress survival. Overall, stress-specific miRNA responses were overserved. Anoxia led to substantial differential miRNA expression patterns, whereas freezing stress showed a relatively high degree of individual variance in miRNA expression. Pathway analysis identified miRNA-related stress survival adaptations, such as cell proliferation. Additionally, machine learning-based gene selection identified seven hepatopancreas miRNAs critical to distinguish between snails under either stress conditions. Our study demonstrated that conserved miRNAs reflect survival adaptations by marine periwinkles under anoxic or frozen conditions, and thus further establishes these snails as an optimal stress model suited for translational research.


Assuntos
MicroRNAs/metabolismo , Caramujos/genética , Estresse Fisiológico/genética , Aclimatação/genética , Animais , Análise por Conglomerados , Congelamento , Hepatopâncreas/metabolismo , Aprendizado de Máquina , RNA-Seq , Caramujos/metabolismo
15.
BMC Genomics ; 21(1): 19, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906861

RESUMO

BACKGROUND: Growth hormone inducible transmembrane protein (GHITM) is a highly conserved transmembrane protein. This study was conducted to investigate the role of GHITM gene in the apoptosis and growth of the golden apple snail Pomacea canaliculate. RESULTS: The complete cDNA of this gene was cloned using the rapid amplification of cDNA ends (RACE) method and subjected to bioinformatics analysis. The full-length cDNA was 2242 bp, including an open reading frame of 1021 bp that encoded a protein of 342 amino acid residues. The mRNA expression profiles of GHITM gene in different tissues (liver, kidney, gonad and foot) and different growth phases (6-months old and 2-years old) showed that it was expressed in various tissues and different growth phases. Silencing of the GHITM gene by RNAi (RNA interference) experiments revealed that the GHITM gene possibly plays a role in inhibiting apoptosis through detecting the Caspase (Cysteine-requiring Aspartate Protease)-3 activity. In addition, the aperture width and body whorl length of the snail was significantly affected by RNAi, suggesting that this gene plays a significant role in promoting the growth of the organism. CONCLUSIONS: These results demonstrated that the GHITM gene was involved in apoptosis and growth in golden apple snail.


Assuntos
Apoptose/genética , Proteínas de Membrana/genética , Fases de Leitura Aberta/genética , Caramujos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/genética , Perfilação da Expressão Gênica/métodos , Proteínas de Membrana/classificação , Proteínas de Membrana/metabolismo , Filogenia , Interferência de RNA , Caramujos/crescimento & desenvolvimento , Caramujos/metabolismo
16.
FASEB J ; 33(3): 3693-3703, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509130

RESUMO

A 13 aa residue voltage-gated sodium (NaV) channel inhibitor peptide, Pn, containing 2 disulfide bridges was designed by using a chimeric approach. This approach was based on a common pharmacophore deduced from sequence and secondary structural homology of 2 NaV inhibitors: Conus kinoshitai toxin IIIA, a 14 residue cone snail peptide with 3 disulfide bonds, and Phoneutria nigriventer toxin 1, a 78 residue spider toxin with 7 disulfide bonds. As with the parent peptides, this novel NaV channel inhibitor was active on NaV1.2. Through the generation of 3 series of peptide mutants, we investigated the role of key residues and cyclization and their influence on NaV inhibition and subtype selectivity. Cyclic PnCS1, a 10 residue peptide cyclized via a disulfide bond, exhibited increased inhibitory activity toward therapeutically relevant NaV channel subtypes, including NaV1.7 and NaV1.9, while displaying remarkable serum stability. These peptides represent the first and the smallest cyclic peptide NaV modulators to date and are promising templates for the development of toxin-based therapeutic agents.-Peigneur, S., Cheneval, O., Maiti, M., Leipold, E., Heinemann, S. H., Lescrinier, E., Herdewijn, P., De Lima, M. E., Craik, D. J., Schroeder, C. I., Tytgat, J. Where cone snails and spiders meet: design of small cyclic sodium-channel inhibitors.


Assuntos
Caramujos/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia , Venenos de Aranha/metabolismo , Aranhas/metabolismo , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Canais de Sódio Disparados por Voltagem/metabolismo , Animais , Oócitos/metabolismo , Peptídeos/farmacologia , Xenopus laevis/metabolismo
17.
Mol Divers ; 24(4): 1291-1299, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502188

RESUMO

Cone snails are slow-moving animals that secure survival by injecting to their prey a concoction of highly potent and stable neurotoxic peptides called conotoxins. These small toxins (~ 10-30 AA) interact with ion channels and their diverse structures account for various variables such as the environment and the prey of preference. This study probed the conformational space of α-conotoxin PnIB from Conus pennaceus by performing all-atom molecular dynamics simulations on the conotoxin in complex solvent systems of water and octanol. Secondary structure analyses showed a uniform conformation for the pure (C100Oc, C100W) and minute (C95Oc, C5Oc) systems. In C50Oc, however, structural changes were observed. The original helices were converted to turns and were shown to happen simultaneously with the elongation of the helix and shortening of end-to-end distance. The transitions complement the orientation of the peptide at the interface. The shift to the broken helix conformation is marked by the rearrangement of solvent molecules to a framework that favors the accumulation of water molecules at residues 6-11 of the H2 region. This promotes specific protein-solvent interactions that facilitate secondary structure transitions. As PnIB has shown favorable binding toward neuronal nicotinic acetylcholine receptors, this study may provide insights on this conotoxin's therapeutic potential. Description: Structural changes in PnIB are accompanied by a simultaneous change in solvent density.


Assuntos
Conotoxinas/química , Conotoxinas/metabolismo , Solventes/química , Animais , Simulação por Computador , Neurônios/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Estrutura Secundária de Proteína , Proteínas/química , Proteínas/metabolismo , Receptores Nicotínicos/química , Receptores Nicotínicos/metabolismo , Caramujos/química , Caramujos/metabolismo
18.
Mar Drugs ; 18(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33371188

RESUMO

The natural products of heterobranch molluscs display a huge variability both in structure and in their bioactivity. Despite the considerable lack of information, it can be observed from the recent literature that this group of animals possesses an astonishing arsenal of molecules from different origins that provide the molluscs with potent chemicals that are ecologically and pharmacologically relevant. In this review, we analyze the bioactivity of more than 450 compounds from ca. 400 species of heterobranch molluscs that are useful for the snails to protect themselves in different ways and/or that may be useful to us because of their pharmacological activities. Their ecological activities include predator avoidance, toxicity, antimicrobials, antifouling, trail-following and alarm pheromones, sunscreens and UV protection, tissue regeneration, and others. The most studied ecological activity is predation avoidance, followed by toxicity. Their pharmacological activities consist of cytotoxicity and antitumoral activity; antibiotic, antiparasitic, antiviral, and anti-inflammatory activity; and activity against neurodegenerative diseases and others. The most studied pharmacological activities are cytotoxicity and anticancer activities, followed by antibiotic activity. Overall, it can be observed that heterobranch molluscs are extremely interesting in regard to the study of marine natural products in terms of both chemical ecology and biotechnology studies, providing many leads for further detailed research in these fields in the near future.


Assuntos
Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Caramujos/metabolismo , Animais , Produtos Biológicos/química , Caramujos/química
19.
Mar Drugs ; 18(2)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32092907

RESUMO

Structure-based tissue engineering requires large-scale 3D cell/tissue manufacture technologies, to produce biologically active scaffolds. Special attention is currently paid to naturally pre-designed scaffolds found in skeletons of marine sponges, which represent a renewable resource of biomaterials. Here, an innovative approach to the production of mineralized scaffolds of natural origin is proposed. For the first time, a method to obtain calcium carbonate deposition ex vivo, using living mollusks hemolymph and a marine-sponge-derived template, is specifically described. For this purpose, the marine sponge Aplysin aarcheri and the terrestrial snail Cornu aspersum were selected as appropriate 3D chitinous scaffold and as hemolymph donor, respectively. The formation of calcium-based phase on the surface of chitinous matrix after its immersion into hemolymph was confirmed by Alizarin Red staining. A direct role of mollusks hemocytes is proposed in the creation of fine-tuned microenvironment necessary for calcification ex vivo. The X-ray diffraction pattern of the sample showed a high CaCO3 amorphous content. Raman spectroscopy evidenced also a crystalline component, with spectra corresponding to biogenic calcite. This study resulted in the development of a new biomimetic product based on ex vivo synthetized ACC and calcite tightly bound to the surface of 3D sponge chitin structure.


Assuntos
Quitina/análogos & derivados , Quitina/química , Hemolinfa/metabolismo , Poríferos/metabolismo , Caramujos/metabolismo , Alicerces Teciduais , Animais , Biomineralização , Carbonato de Cálcio/química , Difração de Raios X
20.
Ecotoxicol Environ Saf ; 189: 110045, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31816499

RESUMO

Phytotoxicity of cadmium (Cd) and its trophic transfer along a terrestrial food chain have been extensively investigated. However, few studies focused on the role of amendments on the trophic transfer of Cd and related mineral nutrients. In a 60-day pot experiment, soil Cd availability, accumulation of Cd, mineral nutrients (Ca and Si) in lettuce, and subsequent trophic transfer along the lettuce-snail system were investigated with or without 3% (w/w) soil amendment (biochar or micro-hydroxyapatite, µHAP). Soil CaCl2 extractable Cd (CdCaCl2) contents decreased by both amendments. µHAP amended soil increased the Freundlich sorption capacity of Cd2+ to a greater extent (15.9 mmol/kg) than biochar (12.6 mmol/kg). Cd, Ca and Si accumulation in lettuce tissues (roots and shoots) varied with amendment species and soil Cd levels. Linear regression analysis showed that root Cd contents are negatively correlated with root Ca and Si contents (r2 = 0.96, p < 0.05). But no significant correlation between shoot Cd and lettuce Ca and Si contents was found (p > 0.05). After 15 days snail feeding, nearly 90% content of Cd was found in snail viscera, while nearly 95% content of Ca was found in snail shells. Contents of Si distributed equally in snail tissues. Biomagnification of Cd, Ca and Si (TF > 1) was found in lettuce shoot - snail viscera system. Opposite tendency of TF variation between Cd and nutrient elements (Ca and Si) from shoots to snail tissues indicated that µHAP, rather than biochar, amendment is applicable to remediate soil Cd contamination in our study.


Assuntos
Cádmio/análise , Carvão Vegetal/química , Lactuca/efeitos dos fármacos , Minerais/metabolismo , Poluentes do Solo/análise , Solo/química , Animais , Bioacumulação , Cádmio/metabolismo , Cálcio/metabolismo , Cadeia Alimentar , Lactuca/metabolismo , Silício/metabolismo , Caramujos/efeitos dos fármacos , Caramujos/metabolismo , Poluentes do Solo/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA