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1.
Adv Exp Med Biol ; 1131: 547-604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646526

RESUMO

Ca2+ release activated Ca2+ (CRAC) channels represent a primary pathway for Ca2+ to enter non-excitable cells. The two key players in this process are the stromal interaction molecule (STIM), a Ca2+ sensor embedded in the membrane of the endoplasmic reticulum, and Orai, a highly Ca2+ selective ion channel located in the plasma membrane. Upon depletion of the internal Ca2+ stores, STIM is activated, oligomerizes, couples to and activates Orai. This review provides an overview of novel findings about the CRAC channel activation mechanisms, structure and gating. In addition, it highlights, among diverse STIM and Orai mutants, also the disease-related mutants and their implications.


Assuntos
Canais de Cálcio Ativados pela Liberação de Cálcio , Membrana Celular , Animais , Cálcio/metabolismo , Canais de Cálcio Ativados pela Liberação de Cálcio/sangue , Canais de Cálcio Ativados pela Liberação de Cálcio/genética , Canais de Cálcio Ativados pela Liberação de Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Mutação , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo
2.
Adv Exp Med Biol ; 1131: 699-718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646531

RESUMO

Calcium exchanges and homeostasis are finely regulated between cellular organelles and in response to physiological signals. Besides ionophores, including voltage-gated Ca2+ channels, ionotropic neurotransmitter receptors, or Store-operated Ca2+ entry, activity of regulatory intracellular proteins finely tune Calcium homeostasis. One of the most intriguing, by its unique nature but also most promising by the therapeutic opportunities it bears, is the sigma-1 receptor (Sig-1R). The Sig-1R is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it interacts with several partners involved in ER stress response, or in Ca2+ exchange between the ER and mitochondria. Small molecules have been identified that specifically and selectively activate Sig-1R (Sig-1R agonists or positive modulators) at the cellular level and that also allow effective pharmacological actions in several pre-clinical models of pathologies. The present review will summarize the recent data on the mechanism of action of Sig-1R in regulating Ca2+ exchanges and protein interactions at MAMs and the ER. As MAMs alterations and ER stress now appear as a common track in most neurodegenerative diseases, the intracellular action of Sig-1R will be discussed in the context of the recently reported efficacy of Sig-1R drugs in pathologies like Alzheimer's disease, Parkinson's disease, Huntington's disease, or amyotrophic lateral sclerosis.


Assuntos
Membrana Celular , Estresse do Retículo Endoplasmático , Doenças Neurodegenerativas , Receptores sigma , Membrana Celular/metabolismo , Membrana Celular/patologia , Humanos , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Receptores sigma/metabolismo
3.
Adv Exp Med Biol ; 1141: 1-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571163

RESUMO

Absorption, distribution, and excretion of drugs are involved in drug transport across plasma membrane, most of which are mediated by drug transporters. These drug transporters are generally divided into solute carrier (SLC) family and ATP-binding cassette (ABC) family. These transporters not only mediate transport of therapeutic drugs across membrane but also transport various kinds of endogenous compounds. Thus besides being participated in disposal of drug and its clinical efficacy/toxicity, these transporters also play vital roles in maintaining cell homeostasis via regulating transport of endogenous compounds. This chapter will outline classification of drug transporters, their roles in drug disposal/drug response, and remote communication between tissues/organs.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Proteínas Carreadoras de Solutos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Comunicação Celular , Membrana Celular/metabolismo , Humanos , Preparações Farmacêuticas/metabolismo , Proteínas Carreadoras de Solutos/metabolismo
4.
Phys Chem Chem Phys ; 21(41): 22679-22694, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31595905

RESUMO

Peptide misfolding and aberrant assembly in membranous micro-environments have been associated with numerous neurodegenerative diseases. The biomolecular mechanisms and biophysical implications of these amyloid membrane interactions have been under extensive research and can assist in understanding disease pathogenesis and potential development of rational therapeutics. But, the complex nature and diversity of biomolecular interactions, structural transitions, and dependence on local environmental conditions have made accurate microscopic characterization challenging. In this review, using cases of Alzheimer's disease (amyloid-beta peptide), Parkinson's disease (alpha-synuclein peptide) and Huntington's disease (huntingtin protein), we illustrate existing challenges in experimental investigations and summarize recent relevant numerical simulation studies into amyloidogenic peptide-membrane interactions. In addition we project directions for future in silico studies and discuss shortcomings of current computational approaches.


Assuntos
Biologia Computacional , Lipídeos/química , Doenças Neurodegenerativas , Dobramento de Proteína , Proteínas Amiloidogênicas/metabolismo , Membrana Celular/metabolismo , Simulação por Computador , Humanos , Metabolismo dos Lipídeos , Doenças Neurodegenerativas/fisiopatologia , Peptídeos/metabolismo
5.
J Agric Food Chem ; 67(40): 11044-11052, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545599

RESUMO

Persimmon condensed tannins (PT) are highly polymerized (mDP = 26) and highly galloylated (72%) proanthocyanidins. Its pleiotropic effects in oxidation resistance, neuroprotection, hypolipidemia, and cardio-protection both in vitro and in vivo were widely reported. Because large proanthocyanidins are unlikely to be absorbed in the gastrointestinal tract, it is believed that the interaction of PT with biological membranes may play a crucial role in its biological activities. In the present study, the capacities of PT adsorbing to membrane, partitioning into membrane, and its influence on the membrane fluidity were investigated by fluorescence quenching, isothermal titration calorimetry (ITC) and fluorescence anisotropy measurements in a biomembrane-mimetic system composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE), sphingomyelin (SPM), and cholesterol (CHOL). Besides, the effects of PT on the morphology and integrity of the cell membrane were studied by scanning electron microscopy (SEM) and fluorescence staining in the 3T3-L1 cell model. The results suggested that PT could affect cell membrane rafts domains, destroy the cell membrane morphology, and regulate cell membrane fluidity, which might contribute to its biological effects.


Assuntos
Membrana Celular/química , Diospyros/química , Extratos Vegetais/química , Proantocianidinas/química , Animais , Fenômenos Biofísicos , Membrana Celular/metabolismo , Colesterol/química , Colesterol/metabolismo , Frutas/química , Fluidez de Membrana , Camundongos , Células NIH 3T3 , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Extratos Vegetais/metabolismo , Polimerização , Proantocianidinas/metabolismo , Esfingomielinas/química , Esfingomielinas/metabolismo
6.
Chemosphere ; 235: 1116-1124, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561302

RESUMO

The porous graphitic carbon nitride nanosheets (PCNSs) with high yields were synthesized by using one-step chemical exfoliation method. PCNSs accelerated separation efficiency of photo-generated electron-hole pairs in comparison to bulk graphitic carbon nitride. The PCNS5 (exfoliation for 5 h) exhibited optimal photocatalytic disinfection capability towards Escherichia coli K-12 under simulated solar light irradiation with complete disinfection of 6.5 log10 cfu/mL of E. coil K-12 within 2 h. The enhanced photocatalytic activity of PCNS5 originated from mesoporous nanosheet structure. The possible mechanism of photocatalytic disinfection has proposed that intracellular reactive oxygen species levels and the activities of antioxidant enzymes (e.g., catalase and superoxide dismutase) were enhanced. Transmission electron microscope images observed during photocatalytic disinfection process suggested that the cell membrane was regarded as the first target for oxidation, resulting in a faster leakage of cytoplasmic content and finally degradation of DNA leading to bacterial death. Furthermore, the trapping experiment showed that superoxide radical (•O2-) and holes (h+) were responsible for E. coli K-12 disinfection by PCNS5.


Assuntos
Desinfecção/métodos , Escherichia coli K12/efeitos dos fármacos , Nanoestruturas/química , Nitrilos/toxicidade , Fotólise , Bactérias/efeitos dos fármacos , Membrana Celular/metabolismo , Dano ao DNA , Oxirredução , Porosidade , Espécies Reativas de Oxigênio
8.
Cell Physiol Biochem ; 53(2): 400-412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403270

RESUMO

BACKGROUND/AIMS: Mutations in ABCA4 cause Stargardt macular degeneration, which invariably ends in legal blindness. We studied two common mutants, A1038V (in NBD1) and G1961E (in NBD2), with the purpose of exploring how they interact with the cell's quality control mechanism. The study was designed to determine how these mutants can be rescued. METHODS: We expressed wt and mutant ABCA4 in HEK293 cells and studied the effect of the mutations on trafficking and processing and the ability of correctors to rescue them. We used a combination of western blotting, confocal microscopy and surface biotinylation coupled with pulldown of plasma membrane proteins. RESULTS: G1961E is sensitive to inhibitors of the aggresome, tubacin and the lysosome, bafilomycin A. Both mutants cause a reduction in heat shock protein, Hsp27. Incubation of HEK293 cells expressing the mutants with VX-809, an FDA approved drug for the treatment of cystic fibrosis, increased the levels of A1038V and G1961E by 2- to 3-fold. Importantly, VX-809 increased the levels of both mutants at the plasma membrane suggesting that trafficking had been restored. Transfecting additional Hsp27 to the cells also increased the steady state levels of both mutants. However, in combination with VX-809 the addition of Hsp27 caused a dramatic increase in the protein expression particularly in the G1961 mutant which increased approximately 5-fold. CONCLUSION: Our results provide a new mechanism for the rescue of ABCA4 trafficking mutants based on the restoration of Hsp27. Our results provide a pathway for the treatment of Stargardt disease.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Aminopiridinas/farmacologia , Benzodioxóis/farmacologia , Transportadores de Cassetes de Ligação de ATP/genética , Aminopiridinas/uso terapêutico , Anilidas/farmacologia , Benzodioxóis/uso terapêutico , Membrana Celular/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Proteínas de Choque Térmico HSP27/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Leupeptinas/farmacologia , Lisossomos/metabolismo , Degeneração Macular/congênito , Degeneração Macular/tratamento farmacológico , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Mutação , Transporte Proteico/efeitos dos fármacos
9.
Dokl Biochem Biophys ; 486(1): 216-219, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367825

RESUMO

The direct action of singlet oxygen on the bacteriochlorophyll (BChl) of light-harvesting complexes in the membranes of four species of purple non-sulfur and sulfur photosynthesizing bacteria with and without carotenoids was studied. It was found that BChl in carotenoidless samples is generally more resistant to the action of singlet oxygen compared to the control. It is assumed that carotenoids are not required to protect BChl of bacterial light-harvesting complexes from singlet oxygen, and in the classic work by Griffith et al. [1] the apoptosis process in carotenoidless mutant cells, which involves the destruction of complexes, the appearance of monomeric BChl, and the generation of singlet oxygen caused by BChl, followed by BChl oxidation, was mistakenly attributed to the protective function of carotenoids.


Assuntos
Bactérias/citologia , Bactérias/metabolismo , Bacterioclorofilas/metabolismo , Carotenoides/metabolismo , Membrana Celular/metabolismo , Fotossíntese , Oxigênio Singlete/metabolismo , Estresse Oxidativo
10.
Chem Commun (Camb) ; 55(66): 9869-9872, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31364617

RESUMO

In this work, we designed and synthesized an aggregation-induced emission (AIE)-active tetraphenylethene-decorated pseudo-trisialic acid (TPE3S) and validated its high affinity for Siglecs using microscale thermophoresis techniques. TPE3S was a unique binding-on fluorescent trivalent sialocluster which was successfully utilized for the visualization of Siglecs expressed on the surface of mammalian cells.


Assuntos
Metabolismo dos Carboidratos , Lectinas/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Animais , Membrana Celular/metabolismo , Corantes Fluorescentes/química , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Células PC12 , Ligação Proteica , Ratos
11.
Phys Chem Chem Phys ; 21(41): 22711-22721, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31454001

RESUMO

Peptide appended pillar[5]arene (PAP) is an artificial water channel resembling biological water channel proteins, which has shown a significant potential for designing bioinspired water purification systems. Given that PAP channels need to be incorporated at a high density in membrane matrices, it is critical to examine the role of channel-channel and channel-membrane interactions in governing the structural and functional characteristics of channels. To resolve the atomic-scale details of these interactions, we have carried out atomistic molecular dynamics (MD) simulations of multiple PAP channels inserted in a lipid or a block-copolymer (BCP) membrane matrix. Classical MD simulations on a sub-microsecond timescale showed clustering of channels only in the lipid membrane, but enhanced sampling MD simulations showed thermodynamically-favorable dimerized states of channels in both lipid and BCP membranes. The dimerized configurations of channels, with an extensive buried surface area, were stabilized via interactions between the aromatic groups in the peptide arms of neighboring channels. The conformational metrics characterizing the orientational and structural changes in channels revealed a higher flexibility in the lipid membrane as opposed to the BCP membrane although hydrogen bonds between the channel and the membrane molecules were not a major contributor to the stability of channels in the BCP membrane. We also found that the channels undergo wetting/dewetting transitions in both lipid and BCP membranes with a marginally higher probability of undergoing a dewetting transition in the BCP membrane. Collectively, these results highlight the role of channel dynamics in governing channel-channel and channel-membrane interfacial interactions, and provide atomic-scale insights needed to design stable and functional biomimetic membranes for efficient separations.


Assuntos
Aquaporinas/química , Calixarenos/química , Membrana Celular/química , Aquaporinas/metabolismo , Biomimética , Membrana Celular/metabolismo , Modelos Moleculares , Conformação Molecular , Simulação de Dinâmica Molecular
12.
Nature ; 571(7764): 284-288, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31263273

RESUMO

Hedgehog signalling is fundamental to embryonic development and postnatal tissue regeneration1. Aberrant postnatal Hedgehog signalling leads to several malignancies, including basal cell carcinoma and paediatric medulloblastoma2. Hedgehog proteins bind to and inhibit the transmembrane cholesterol transporter Patched-1 (PTCH1), which permits activation of the seven-transmembrane transducer Smoothened (SMO) via a mechanism that is poorly understood. Here we report the crystal structure of active mouse SMO bound to both the agonist SAG21k and to an intracellular binding nanobody that stabilizes a physiologically relevant active state. Analogous to other G protein-coupled receptors, the activation of SMO is associated with subtle motions in the extracellular domain, and larger intracellular changes. In contrast to recent models3-5, a cholesterol molecule that is critical for SMO activation is bound deep within the seven-transmembrane pocket. We propose that the inactivation of PTCH1 by Hedgehog allows a transmembrane sterol to access this seven-transmembrane site (potentially through a hydrophobic tunnel), which drives the activation of SMO. These results-combined with signalling studies and molecular dynamics simulations-delineate the structural basis for PTCH1-SMO regulation, and suggest a strategy for overcoming clinical resistance to SMO inhibitors.


Assuntos
Membrana Celular/química , Proteínas Hedgehog/agonistas , Transdução de Sinais/efeitos dos fármacos , Receptor Smoothened/agonistas , Receptor Smoothened/metabolismo , Esteróis/farmacologia , Animais , Sítios de Ligação , Técnicas Biossensoriais , Domínio Catalítico/efeitos dos fármacos , Membrana Celular/metabolismo , Colesterol/química , Colesterol/metabolismo , Colesterol/farmacologia , Proteínas Hedgehog/metabolismo , Ligantes , Camundongos , Modelos Moleculares , Simulação de Dinâmica Molecular , Receptor Patched-1/antagonistas & inibidores , Receptor Patched-1/metabolismo , Conformação Proteica , Estabilidade Proteica , Anticorpos de Cadeia Única/imunologia , Receptor Smoothened/antagonistas & inibidores , Receptor Smoothened/química , Esteróis/química , Esteróis/metabolismo , Proteínas de Xenopus/química
13.
Cancer Sci ; 110(9): 2856-2866, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31314163

RESUMO

4-Hydroxynonenal (HNE) is an important product of plasma membrane lipid peroxidation, which is a cause of cell and tissue injury. Mitochondrial DNA (mtDNA)-depleted ρ0 cells were established using human cervical cancer and oral squamous cell carcinoma cell lines. We investigated the effect of reactive oxygen species in ρ0 cells, especially the mechanism of hydrogen peroxide (H2 O2 )-mediated cell death. These cell were subjected to high oxidative stress and, compared with their parental cells, showed greater sensitivity to H2 O2 and high lipid peroxidation. Upregulation of HNE in the plasma membrane was observed prior to the increase in intracellular H2 O2 . The amount of oxidized lipid present changed H2 O2 permeability and administration of oxidized lipid led to further cell death after treatment with H2 O2 . Expression levels of lipoxygenase ALOX genes (ie ALOX5, ALOX12, and ALOX15) were upregulated in ρ0 cells, as were expression levels of ALOX12 and ALOX15 proteins. ALOX5 protein was mainly distributed in the nucleus, while ALOX12 and ALOX15 proteins were distributed in the nucleus and the cytoplasm. Although expression of COX2 gene was upregulated, its protein expression did not increase. ALOX (especially ALOX15) may be involved in the sensitivity of cancer cells to treatment. These data offer promise for the development of novel anticancer agents by altering the oxidation state of the plasma membrane. Our results showed that lipid peroxidation status is important for H2 O2 sensitivity and that ALOX15 is involved in lipid peroxidation status.


Assuntos
Apoptose/efeitos dos fármacos , Permeabilidade da Membrana Celular/genética , DNA Mitocondrial/genética , Peróxido de Hidrogênio/administração & dosagem , Peroxidação de Lipídeos/genética , Neoplasias/patologia , Aldeídos/metabolismo , Araquidonato 15-Lipoxigenase/metabolismo , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacocinética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Estresse Oxidativo/efeitos dos fármacos , Éteres Fosfolipídicos/administração & dosagem , Regulação para Cima
14.
Nat Commun ; 10(1): 2946, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270421

RESUMO

The capability to encapsulate designated live cells into a biologically and mechanically tunable polymer layer is in high demand. Here, an approach to weave functional DNA polymer cocoons has been proposed as an encapsulation method. By developing in situ DNA-oriented polymerization (isDOP), we demonstrate a localized, programmable, and biocompatible encapsulation approach to graft DNA polymers onto live cells. Further guided by two mutually aided enzymatic reactions, the grafted DNA polymers are assembled into DNA polymer cocoons at the cell surface. Therefore, the coating of bacteria, yeast, and mammalian cells has been achieved. The capabilities of this approach may offer significant opportunities to engineer cell surfaces and enable the precise manipulation of the encapsulated cells, such as encoding, handling, and sorting, for many biomedical applications.


Assuntos
Células Imobilizadas/citologia , DNA/química , Polímeros/química , Membrana Celular/metabolismo , Sobrevivência Celular , Células Imobilizadas/metabolismo , Humanos , Células MCF-7 , Polimerização
15.
World J Microbiol Biotechnol ; 35(8): 124, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31346773

RESUMO

Candida glabrata is a haploid yeast that is considered to be an emergent pathogen since it is the second most prevalent cause of candidiasis. Contrary to most yeasts, this species carries only one plasma membrane potassium transporter named CgTrk1. We show in this work that the activity of this transporter is regulated at the posttranslational level, and thus Trk1 contributes to potassium uptake under very different external cation concentrations. In addition to its function in potassium uptake, we report a diversity of physiological effects related to this transporter. CgTRK1 contributes to proper cell size, intracellular pH and membrane-potential homeostasis when expressed in Saccharomyces cerevisiae. Moreover, lithium influx experiments performed both in C. glabrata and S. cerevisiae indicate that the salt tolerance phenotype linked to CgTrk1 can be related to a high capacity to discriminate between potassium and lithium (or sodium) during the transport process. In summary, we show that CgTRK1 exerts a diversity of pleiotropic physiological roles and we propose that the corresponding protein may be an attractive pharmacological target for the development of new antifungal drugs.


Assuntos
Candida glabrata/genética , Proteínas de Transporte de Cátions/genética , Proteínas Fúngicas/genética , Candida glabrata/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Membrana Celular/metabolismo , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Homeostase , Concentração de Íons de Hidrogênio , Potássio/metabolismo , Sódio/metabolismo
16.
J Nanobiotechnology ; 17(1): 81, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286976

RESUMO

BACKGROUND: Magnetic nanoparticles (MNPs) are characterized by unique physicochemical and biological properties that allow their employment as highly biocompatible drug carriers. Gelsolin (GSN) is a multifunctional actin-binding protein involved in cytoskeleton remodeling and free circulating actin sequestering. It was reported that a gelsolin derived phosphoinositide binding domain GSN 160-169, (PBP10 peptide) coupled with rhodamine B, exerts strong bactericidal activity. RESULTS: In this study, we synthesized a new antibacterial and antifungal nanosystem composed of MNPs and a PBP10 peptide attached to the surface. The physicochemical properties of these nanosystems were analyzed by spectroscopy, calorimetry, electron microscopy, and X-ray studies. Using luminescence based techniques and a standard killing assay against representative strains of Gram-positive (Staphylococcus aureus MRSA Xen 30) and Gram-negative (Pseudomonas aeruginosa Xen 5) bacteria and against fungal cells (Candida spp.) we demonstrated that magnetic nanoparticles significantly enhance the effect of PBP10 peptides through a membrane-based mode of action, involving attachment and interaction with cell wall components, disruption of microbial membrane and increased uptake of peptide. Our results also indicate that treatment of both planktonic and biofilm forms of pathogens by PBP10-based nanosystems is more effective than therapy with either of these agents alone. CONCLUSIONS: The results show that magnetic nanoparticles enhance the antimicrobial activity of the phosphoinositide-binding domain of gelsolin, modulate its mode of action and strengthen the idea of its employment for developing the new treatment methods of infections.


Assuntos
Antibacterianos/química , Antifúngicos/química , Gelsolina/química , Nanopartículas de Magnetita/química , Fragmentos de Peptídeos/química , Biofilmes , Candida/efeitos dos fármacos , Membrana Celular/metabolismo , Ouro/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanoconchas/química , Plâncton , Pseudomonas aeruginosa/efeitos dos fármacos , Rodaminas/química
17.
Cancer Invest ; 37(7): 293-298, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31328584

RESUMO

The aim of the study is to analyse the expression of Interleukin-6 receptor in different human gastric tissue and to correlate with the clinicopathological features of the patients. Immunohistochemistry was done against the IL-6R antibody and the Q-score was calculated from the staining pattern. Higher Q-scores were observed in tumour cells than the adjacent normal cells which were statistically significant. We also observed a significant correlation between the expressions of IL-6R and the clinicopathological features These findings suggest that IL-6R may represent as a therapeutic target for gastric carcinoma and serve as a prognostic indicator, as well.


Assuntos
Biomarcadores Tumorais/metabolismo , Receptores de Interleucina-6/metabolismo , Neoplasias Gástricas/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Celular/metabolismo , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Nat Commun ; 10(1): 3073, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300643

RESUMO

Many organisms regulate their social life through kin recognition, but the underlying mechanisms are poorly understood. Here, we use a social bacterium, Myxococcus xanthus, to investigate kin recognition at the molecular level. By direct visualization of a cell surface receptor, TraA, we show how these myxobacteria identify kin and transition towards multicellularity. TraA is fluid on the cell surface, and homotypic interactions between TraA from juxtaposed cells trigger the receptors to coalesce, representing a 'molecular handshake'. Polymorphisms within TraA govern social recognition such that receptors cluster only between individuals bearing compatible alleles. TraA clusters, which resemble eukaryotic gap junctions, direct the robust exchange of cellular goods that allows heterogeneous populations to transition towards homeostasis. This work provides a conceptual framework for how microbes use a fluid outer membrane receptor to recognize and assemble kin cells into a cooperative multicellular community that resembles a tissue.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Membrana Celular/metabolismo , Myxococcus xanthus/fisiologia , Percepção de Quorum/fisiologia , Receptores de Superfície Celular/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Polimorfismo Genético , Receptores de Superfície Celular/genética
19.
Phys Chem Chem Phys ; 21(35): 18830-18838, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31322147

RESUMO

In biomedical technologies that use nanoparticles, the nanoparticles are often required to translocate across a cell membrane. Application of an external electric field has been used to increase the cell membrane permeability; however, damage to the cell is of great concern. Using a molecular dynamics simulation, we show that even under a weak external electric field that is lower than the membrane breakdown intensity, a cationic nanoparticle will directly translocate across a model cell membrane without membrane disruption. We then reveal its physical mechanism. At the contact interface between the nanoparticle and the cell membrane, the electric potential across the membrane is locally enhanced by superimposing the nanoparticle surface potential on the externally applied potential, resulting in its direct translocation. Our finding implies that, by controlling the nanoparticle-induced local enhancement of the membrane potential, the cellular delivery of nanoparticles via a non-endocytic and non-disruptive pathway can be realized.


Assuntos
Membrana Celular/metabolismo , Nanopartículas/metabolismo , Cátions/metabolismo , Fenômenos Eletrofisiológicos , Potenciais da Membrana , Membranas Artificiais , Simulação de Dinâmica Molecular
20.
Chemistry ; 25(54): 12452-12463, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31304989

RESUMO

Light-inducible approaches provide a means to control biological systems with spatial and temporal resolution that is unmatched by traditional genetic perturbations. Recent developments of optogenetic and chemo-optogenetic systems for induced proximity in cells facilitate rapid and reversible manipulation of highly dynamic cellular processes and have become valuable tools in diverse biological applications. New expansions of the toolbox facilitate control of signal transduction, genome editing, "painting" patterns of active molecules onto cellular membranes, and light-induced cell cycle control. A combination of light- and chemically induced dimerization approaches have also seen interesting progress. Herein, an overview of optogenetic systems and emerging chemo-optogenetic systems is provided, and recent applications in tackling complex biological problems are discussed.


Assuntos
Fenômenos Fisiológicos Celulares , Optogenética/métodos , Proteínas/química , Proteínas/metabolismo , Animais , Membrana Celular/metabolismo , Regulação da Expressão Gênica , Humanos , Cinética , Luz , Mutação , Multimerização Proteica , Proteínas/genética
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