RESUMO
Stress inducible protein 1 (STI1) is a co-chaperone acting with Hsp70 and Hsp90 for the correct client proteins' folding and therefore for the maintenance of cellular homeostasis. Besides being expressed in the cytosol, STI1 can also be found both in the cell membrane and the extracellular medium playing several relevant roles in the central nervous system (CNS) and tumor microenvironment. During CNS development, in association with cellular prion protein (PrPc), STI1 regulates crucial events such as neuroprotection, neuritogenesis, astrocyte differentiation and survival. In cancer, STI1 is involved with tumor growth and invasion, is undoubtedly a pro-tumor factor, being considered as a biomarker and possibly therapeutic target for several malignancies. In this review, we discuss current knowledge and new findings on STI1 function as well as its role in tissue homeostasis, CNS and tumor progression.
Assuntos
Chaperonas Moleculares , Proteínas de Choque Térmico , Humanos , Microambiente TumoralRESUMO
BACKGROUND: Peroxisome proliferator-activated receptor γ (PPAR-γ) agonists have received much attention in research because of their neuroprotective and anti-inflammatory effects that reduce cell death and halt the progression of neurodegeneration. Thus, this study observed the pioglitazone effects on the main inflammatory markers after 6-hydroxydopamine (6-OHDA) lesion. METHODS: The effects of a 5-day administration of the PPAR-γ agonist pioglitazone (30 mg/kg) in male Wistar rats that received bilateral intranigral infusions of 6-OHDA. After surgery, the rats were evaluated in the open-field test on days 1,7,14, and 21. Immediately after the behavioral tests on day 21, the rats were euthanized, and the substantia nigra was removed to analyze the expression of nuclear factor κB (NF-κB) and IκB by western blot. To immunohistochemical, animals were intracardially perfused, with brain removal that was frozen and sectioned, being selected slices of the SNc region to detect tyrosine hydroxylase (TH) immunoreactivity, microglia activation (Iba-1) and NF-κB translocation in the nucleus. RESULTS: Pioglitazone protected rats against hypolocomotion and 6-OHDA-induced dopaminergic neurodegeneration on day 7. Decreases in the microglial activation and the NF-κB expression were observed, and the p65 activation was inhibited. CONCLUSIONS: These results suggest that pioglitazone may be a potential adjuvant for the treatment of Parkinson`s disease because of its effects on pathological markers of the progression of neurodegeneration.
Assuntos
Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/uso terapêutico , PPAR gama/agonistas , Doença de Parkinson/tratamento farmacológico , Pioglitazona/uso terapêutico , Substância Negra/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Masculino , Microglia/patologia , Atividade Motora/efeitos dos fármacos , Oxidopamina , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Ratos Wistar , Substância Negra/metabolismoRESUMO
Quinolones and fluoroquinolones are widely used to treat uropathogenic Escherichia coli infections. Bacterial resistance to these antimicrobials primarily involves mutations in gyrA and parC genes. To date, no studies have examined the potential relationship between biochemical characteristics and quinolone resistance in uropathogenic E. coli strains. The present work analyzed the quinolone sensitivity and biochemical activities of fifty-eight lactose-negative uropathogenic E. coli strains. A high percentage of the isolates (48.3%) was found to be resistant to at least one of the tested quinolones, and DNA sequencing revealed quinolone resistant determining region gyrA and parC mutations in the multi-resistant isolates. Statistical analyses suggested that the lack of ornithine decarboxylase (ODC) activity is correlated with quinolone resistance. Despite the low number of isolates examined, this is the first study correlating these characteristics in lactose-negative E. coli isolates.
Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Infecções por Escherichia coli/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Lactose/metabolismo , Ácido Nalidíxico/uso terapêutico , Ornitina Descarboxilase/genética , Infecções Urinárias/tratamento farmacológico , Escherichia coli Uropatogênica/genética , Antibacterianos/uso terapêutico , Brasil , DNA Girase/genética , DNA Topoisomerase IV/genética , Descarboxilação/genética , Descarboxilação/fisiologia , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Ornitina/metabolismo , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/enzimologia , Escherichia coli Uropatogênica/isolamento & purificaçãoRESUMO
Quinolones and fluoroquinolones are widely used to treat uropathogenic
Assuntos
Humanos , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Escherichia coli/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Lactose/metabolismo , Ácido Nalidíxico/uso terapêutico , Ornitina Descarboxilase/genética , Infecções Urinárias/tratamento farmacológico , Escherichia coli Uropatogênica/genética , Antibacterianos/uso terapêutico , Brasil , DNA Girase/genética , DNA Topoisomerase IV/genética , Descarboxilação/genética , Descarboxilação/fisiologia , Infecções por Escherichia coli/microbiologia , Testes de Sensibilidade Microbiana , Ornitina/metabolismo , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/enzimologia , Escherichia coli Uropatogênica/isolamento & purificaçãoRESUMO
Quinolones and fluoroquinolones are widely used to treat uropathogenic Escherichia coli infections. Bacterial resistance to these antimicrobials primarily involves mutations in gyrA and parC genes. To date, no studies have examined the potential relationship between biochemical characteristics and quinolone resistance in uropathogenic E. coli strains. The present work analyzed the quinolone sensitivity and biochemical activities of fifty-eight lactose-negative uropathogenic E. coli strains. A high percentage of the isolates (48.3%) was found to be resistant to at least one of the tested quinolones, and DNA sequencing revealed quinolone resistant determining region gyrA and parC mutations in the multi-resistant isolates. Statistical analyses suggested that the lack of ornithine decarboxylase (ODC) activity is correlated with quinolone resistance. Despite the low number of isolates examined, this is the first study correlating these characteristics in lactose-negative E. coli isolates.(AU)
Assuntos
Humanos , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Escherichia coli/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Lactose/metabolismo , Ácido Nalidíxico/uso terapêutico , Ornitina Descarboxilase/genética , Escherichia coli Uropatogênica/genética , Antibacterianos/uso terapêutico , Brasil , DNA Girase/genética , DNA Topoisomerase IV/genética , Descarboxilação/genética , Descarboxilação/fisiologia , Infecções por Escherichia coli/microbiologia , Testes de Sensibilidade Microbiana , Ornitina/metabolismo , /microbiologia , Escherichia coli Uropatogênica , Escherichia coli Uropatogênica/enzimologia , Escherichia coli Uropatogênica/isolamento & purificaçãoRESUMO
The aim of this study was establish a protocol for isolation and primary culture of neurons from tropical freshwater fish species Hoplias malabaricus for assessment of the effects of neurotoxic substances as saxitoxins (STXs). Cells from brain of H. malabaricus were treated with different concentrations of trypsin, dispase and papain for tissue dissociation. Cells type was separated by cellular gradient and basic fibroblast growth factor (bFGF) supplement nutrition media were added. The dissociated cells were plated with medium and different STXs concentrations and the toxic cellular effects such as oxidative stress, neurotoxicity, and genotoxicity and apoptosis process were evaluated. Cultures treated with bFGF showed the greatest adherence, survival and cellular development. STXs increased specific activity of glutathione peroxidase and lipoperoxidation levels, were cytotoxic and genotoxic indicated by the comet assay. Although the STXs effects due the blockage of sodium channels is reported to be reversible, the time exposure and concentration of STXs suggested cellular injuries which can lead to neuropathology. The establishment of primary neuronal culture protocol enables new applications for neurotoxicological assessments.
Assuntos
Linguados , Neurônios/efeitos dos fármacos , Estresse Oxidativo , Saxitoxina/toxicidade , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Técnicas de Cultura de Células , Neurônios/citologiaRESUMO
Rnd proteins comprise a branch of the Rho family of small GTP-binding proteins, which have been implicated in rearrangements of the actin cytoskeleton and microtubule dynamics. Particularly in the nervous system, Rnd family proteins regulate neurite formation, dendrite development and axonal branching. A secreted form of the co-chaperone Stress-Inducible Protein 1 (STI1) has been described as a prion protein partner that is involved in several processes of the nervous system, such as neurite outgrowth, neuroprotection, astrocyte development, and the self-renewal of neural progenitor cells. We show that cytoplasmic STI1 directly interacts with the GTPase Rnd1. This interaction is specific for the Rnd1 member of the Rnd family. In the COS collapse assay, overexpression of STI1 prevents Rnd1-plexin-A1-mediated cytoskeleton retraction. In PC-12 cells, overexpression of STI1 enhances neurite outgrowth in cellular processes initially established by Rnd1. Therefore, we propose that STI1 participates in Rnd1-induced signal transduction pathways that are involved in the dynamics of the actin cytoskeleton.
Assuntos
Citoesqueleto/metabolismo , Proteínas de Choque Térmico/fisiologia , Neuritos/fisiologia , Proteínas rho de Ligação ao GTP/fisiologia , Animais , Células COS , Células Cultivadas , Chlorocebus aethiops , Camundongos , Microtúbulos/metabolismo , Células PC12 , Ligação Proteica , Ratos , Transdução de Sinais/fisiologiaRESUMO
Broilers and layer chickens have been intensively selected for production parameters. This selection has affected immune capacity. Consequently, the fine-tuning of immune responses is becoming important for maximum productivity. Flow cytometry is a recurrent technology used for the immunophenotyping of birds. Studies, however, have focused on the mechanism of specific diseases or have used animals whose immunological condition could be biased-by vaccination or environmental stressors, for example. The aim of this study was to evaluate the immune status of specific-pathogen-free birds across different age ranges to characterize the natural changes that occur over time. Additionally, specific-pathogen-free chickens were challenged with four infectious agents, allowing identification of the subpopulations of peripheral blood immune cells that are consistently altered under various conditions. Several lymphocyte subsets vary naturally with aging, so the interpretation of results using animals of different age ranges must proceed with care. Parameters such as CD8(+)CD28(-), CD8αα(+), CD4(+)CD8(+), and CD8(+)TCRVß1(+) have been shown to be valuable in understanding immune changes during disease. The use of these data allows a determination of the consistency of cytometric parameters under various conditions, which should ease the interpretation of immunophenotyping and the future application of cytometric analysis in the poultry industry.
Assuntos
Galinhas/imunologia , Citometria de Fluxo/veterinária , Doenças das Aves Domésticas/imunologia , Fatores Etários , Animais , Infecções por Birnaviridae/imunologia , Infecções por Birnaviridae/veterinária , Coccidiose/imunologia , Coccidiose/veterinária , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Eimeria/imunologia , Feminino , Imunidade Celular/imunologia , Imunofenotipagem/veterinária , Vírus da Bronquite Infecciosa/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Valores de Referência , Salmonelose Animal/imunologia , Salmonella enteritidis/imunologiaRESUMO
Different Parkinson's disease (PD) animal models reproduce the early phase of the disease, which deny the possible existence of a synergic effect of consecutive insults to the dopaminergic neurons. We proposed a novel protocol of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nigrostriatal lesion, which consists in repeated MPTP intranigral administrations intending to differentiate effects of a single lesion in relation to repeated lesions. For this purpose, a schedule of 3-day intervals between the MPTP administrations, totalizing 3 infusions in 9 days were adopted. A persistent locomotor deficit was produced after the 2nd infusion, remaining until the last time-point. Tyrosine hydroxylase (TH) immunoreactive neurons were reduced in 50% 1 day after the 1st infusion and the neuronal loss remained constant even after the 2nd and 3rd MPTP infusions. In parallel, (TH) protein expression in the substantia nigra pars compacta (SNpc) revealed to be a sensitive target for MPTP, once it was found to be down-regulated immediately after the 1st MPTP exposure until the last time-point. These findings corroborate the concept of an early phase model of PD elicited by MPTP even when this neurotoxin was used according to the protocol currently proposed. The current protocol provided relevant insights about TH expression and irreversible locomotor impairment.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/administração & dosagem , Atividade Motora/efeitos dos fármacos , Neurotoxinas/administração & dosagem , Doença de Parkinson/etiologia , Doença de Parkinson/fisiopatologia , Substância Negra/efeitos dos fármacos , Análise de Variância , Animais , Comportamento Animal , Modelos Animais de Doenças , Esquema de Medicação , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
A conversäo da proteína príon celular (PrPc) em sua isoforma anormal PrPsc está associada a uma série de doenças neurodegenerativas, genericamente designadas por doenças priônicas. Embora a literatura tenha enfatizado o estudo do PrPsc e o mecanismo de propagaçäo das doenças de príon, pouco tem sido feito para o entendimento do papel fisiológico do PrPc. Em 1997 nosso grupo descreveu um receptor/ligante para o PrPc utilizando o princípio da hidropaticidade complementar. Neste trabalho isolamos e identificamos este ligante de PrPc como sendo a STI-1 (Stress Inducible Protein-1). In vitro, a STI-1 interage com o PrPc de maneira específica, saturável e com alta afinidade (Kd=8x10-8M)...