RESUMEN
Fish, like many other animals, panic when another individual is injured. Now, the chemical nature of a substance that mediates this reaction has been uncovered.
Asunto(s)
Condroitín/fisiología , Miedo/fisiología , Odorantes , Pez Cebra/fisiología , AnimalesRESUMEN
The ability to detect and avoid predators is essential to survival. Various animals, from sea urchins to damselfly larvae, use injury of conspecifics to infer the presence of predators. In many fish, skin damage causes the release of chemicals that elicit escape and fear in members of the shoal. The chemical nature of the alarm substance ("Schreckstoff" in German), the neural circuits mediating the complex response, and the evolutionary origins of a signal with little obvious benefit to the sender, are unresolved. To address these questions, we use biochemical fractionation to molecularly characterize Schreckstoff. Although hypoxanthine-3 N-oxide has been proposed to be the alarm substance, it has not been reliably detected in the skin and there may be other active components. We show that the alarm substance is a mixture that includes the glycosaminoglycan (GAG) chondroitin. Purified chondroitins trigger fear responses. Like skin extract, chondroitins activate the mediodorsal posterior olfactory bulb, a region innervated by crypt neurons that has a unique projection to the habenula. These findings establish GAGs as a new class of odorants in fish, which trigger alarm behavior possibly via a specialized circuit.
Asunto(s)
Condroitín/fisiología , Miedo/fisiología , Odorantes , Pez Cebra/fisiología , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Condroitín/química , Condroitín/farmacología , Miedo/efectos de los fármacos , Odorantes/análisis , Bulbo Olfatorio/efectos de los fármacos , Bulbo Olfatorio/fisiología , Piel/químicaRESUMEN
In Caenorhabditis elegans hermaphrodites, the U-shaped gonad arms are formed by directed migration of the gonadal distal tip cells (DTCs). The stereotyped pattern of DTC migration is carefully controlled by extracellular and cell surface molecules during larval development. Here we report that two proteins, SQV-5 (chondroitin synthase) and its cofactor MIG-22 (chondroitin polymerizing factor), are required for chondroitin biosynthesis and are essential for the dorsally guided migration of DTCs. We found that MIG-22 is expressed in migrating DTCs, hypodermal seam cells, developing vulva and oocytes. The expression of SQV-5 or MIG-22 in both DTCs and hypodermis rescued the DTC migration defects of the relevant mutants more efficiently than when they were expressed in either single tissue. Furthermore, the expression of SQV-5 by the mig-22 promoter significantly rescued sqv-5 mutants, implying that these two proteins act in the same tissues and that chondroitin proteoglycans produced in both of these tissues are required for DTC migration. The DTC migration defects caused by sqv-5 or mig-22 mutations were partially suppressed in the anterior and enhanced in the posterior DTCs in unc-6, unc-5 or unc-40 mutant backgrounds, suggesting that chondroitin proteoglycans play roles in the UNC-6/netrin-dependent guidance of DTCs.
Asunto(s)
Caenorhabditis elegans/embriología , Movimiento Celular/fisiología , Condroitín/fisiología , Ovario/embriología , Testículo/embriología , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Movimiento Celular/genética , Femenino , Glicosiltransferasas/genética , Masculino , Datos de Secuencia Molecular , Ovario/citología , Ovario/metabolismo , Testículo/citología , Testículo/metabolismoRESUMEN
During rat brain development, striatal proteoglycan (PG) expression shows specific spatio-temporal modifications suggesting a possible role in the guidance of its dopaminergic afferents. The effects of individual glycosaminoglycans (GAGs) on dopaminergic (DA) neuronal adhesion and outgrowth were therefore studied. We tested the behavior of dissociated embryonic rat mesencephalic cells cultivated on substrate-bound GAGs. Neuronal attachment was very limited and quantitative morphometry revealed variations in DA fiber outgrowth depending on the type and the concentration of GAG used. Next, we developed a cryoculture system to examine how neurons react toward GAGs expressed in situ. Rat brain slices from different developmental stages were used as substrates for embryonic mesencephalic explants. Preferential regions of adherence and outgrowth were observed: the striatum was found to be the most permissive, whereas the cortex was inhibitory. Western blotting experiments confirmed quantitative and qualitative changes in chondroitin sulfate (neurocan, phosphacan) and keratan sulfate (KS) containing PGs in these substrates and enzymatic digestion of GAGs before cryoculture revealed a substantial involvement of PGs in DA neuron adhesion and outgrowth. In particular, CSPGs seemed to mediate the permissive effect of the striatum, whereas KS confers an inhibitory effect to the cortex. PGs may thus be important for limiting midbrain projections to the striatum during development and for maintaining topography in the adult.
Asunto(s)
Condroitín/fisiología , Sulfato de Queratano/fisiología , Mesencéfalo/fisiología , Animales , Animales Recién Nacidos , Western Blotting , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , Condroitín/farmacología , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Cuerpo Estriado/crecimiento & desarrollo , Cuerpo Estriado/metabolismo , Cuerpo Estriado/fisiología , Técnicas Citológicas , Dopamina/fisiología , Glicosaminoglicanos/farmacología , Glicosaminoglicanos/fisiología , Inmunohistoquímica , Sulfato de Queratano/farmacología , Laminina/fisiología , Lectinas Tipo C , Mesencéfalo/efectos de los fármacos , Mesencéfalo/crecimiento & desarrollo , Proteínas del Tejido Nervioso/metabolismo , Neuritas/efectos de los fármacos , Neuritas/fisiología , Neurocano , Técnicas de Cultivo de Órganos , Péptidos/fisiología , Ratas , Ratas Sprague-Dawley , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
O HIV-1 infecta células T CD4+ e macrófagos através da interação entre a glicoprotéina do envelope viral com a molécula CD4 e um receptor de quimiocina. O receptor de a-quimiocina CXCR4 é o correceptor para isolados de HIV-1 trópicos para células T CD4+ tumorais, enquanto cepas de HIV-l trópicos para macrófagos usam os receptores de β-quimiocina CCR2B, CCR3 e CCR5. Como vários polissacarídeos sulfatados apresentam atividade anti-HIV-1, in vitro, nós decidimos investigar se a condroitina sulfatada fucosilada (CSF), um polissacarídeo sulfatado natural derivado de um equinodermo, poderia neutralizar a infecção pelo HIV-1 mediada por isolados trópicos para CCR5 (R5), CXCR4 (X4) e CCR5/CXCR4 (R5X4), e comparar a atividade anti-HIV-l com a do dextran sulfato (DS). Para testar o efeito inibitório sobre isolados X4 e R5X4, realizamos ensaios de inibição da formação de sincícios entre células PM-l cronicamente infectadas por estes vírus com células T CD4+ tumorais (PM-l e MT-2) não-infectadas. A infecção pelo HIV-1 foi avaliada pela inibição do efeito citopático, o qual foi determinado pelo método colorimétrico XTT. Observamos que seis dos sete isolados X4 foram fortemente inibidos pelo CSF, enquanto quatro dos cinco isolados R5X4 foram neutralizados em ambas as células-alvo. Isolados R5 foram estudados infectando-se células U87 transfectadas com as moléculas CD4 e CCR5, na presença ou não do CSF. A replicação viral foi avaliada pela medida da atividade da enzima transcriptase reversa nos sobrenadantes de cultura. Vimos que cinco dos seis isolados testados foram fortemente bloqueados pelo CSF. Em conclusão, encontramos que o CSF foi mais eficiente quando a...
Asunto(s)
Humanos , Condroitín/fisiología , VIH , Seropositividad para VIH , VIH-1 , PolisacáridosRESUMEN
Proteoglycans are an important nonfibrous matrix component of the arterial wall. Direct evidence for their role in resistance-sized arteries is lacking, although they likely have an important role in coordinating and regulating vessel behavior, presumably via interactions of their glycosaminoglycan chains or core proteins with other matrix molecules and/or the smooth muscle cell surface. The purpose of this study was to determine whether the removal of specific glycosaminoglycan chains from proteoglycans in resistance-sized mesenteric arteries would change the mechanical properties of the arterial wall, thereby affecting their functional behavior. The major finding of the study was that 65% removal of chondroitin-dermatan sulfate-containing glycosaminoglycans from the arterial wall increased vascular wall stiffness and altered the myogenic behavior of the artery. The significant alterations in myogenic behavior associated with changes in passive mechanics following partial glycosaminoglycan chain removal support our hypothesis that chondroitin-dermatan sulfate-containing proteoglycans contribute significantly to the functional behavior of resistance arteries. We speculate that these alterations are the result of changes in stress transfer between collagen fibrils and/or stress transfer between cells and collagen fibrils under applied pressure.