RESUMEN
This study aimed to examine the evidence of direct interaction among actin, myosin and phosphatidylinositol 3-kinase (PI3K) in the polarisation and formation of the tetraspore germ tube of Gelidium floridanum. After release, tetraspores were exposed to cytochalasin B, latrunculin B, LY294002 and BDM for a period of 6 h. In control samples, formation of the germ tube occurred after the experimental period, with cellulose formation and elongated chloroplasts moving through the tube region in the presence of F-actin. In the presence of cytochalasin B, an inhibitor of F-actin, latrunculin B, an inhibitor of G-actin, and BDM, a myosin inhibitor, tetraspores showed no formation of the germ tube or cellulose. Spherical-shaped chloroplasts were observed in the central region with a few F-actin filaments in the periphery of the cytoplasm. Tetraspores treated with LY294002, a PI3K inhibitor, showed no formation of the tube at the highest concentrations. Polarisation of cytoplasmic contents did not occur, only cellulose formation. It was concluded that F-actin directs the cell wall components and contributes to the maintenance of chloroplast shape and elongation during germ tube formation. PI3K plays a fundamental role in signalling for the asymmetric polarisation of F-actin. Thus, F-actin regulates the polarisation and germination processes of tetraspores of G. floridanum.
Asunto(s)
Citoesqueleto de Actina/metabolismo , Miosinas/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Rhodophyta/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Pared Celular/metabolismo , Cloroplastos/metabolismo , Cromonas/farmacología , Citocalasinas , Diacetil/análogos & derivados , Diacetil/farmacología , Morfolinas/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Estructuras de las Plantas/crecimiento & desarrollo , Estructuras de las Plantas/metabolismo , Rhodophyta/efectos de los fármacos , Rhodophyta/crecimiento & desarrollo , Tiazolidinas/farmacologíaRESUMEN
BACKGROUND AND PURPOSE: Kinins are pro-inflammatory peptides that are released during tissue injury, including that caused by inflammatory bowel disease. Herein, we assessed the role and underlying mechanisms through which the absence of kinin B(1) receptors exacerbates the development of dextran sulfate sodium (DSS)-induced colitis in mice. EXPERIMENTAL APPROACH: B(1) and B(2) receptor antagonists and B(1) receptor knockout mice (B1(-/-) ) were used to assess the involvement of B(1) and B(2) receptor signalling in a DSS-colitis. B(1) receptor, B(2) receptor, occludin and claudin-4 expression, cytokine levels and cell permeability were evaluated in colon from wild-type (WT) and B1(-/-) mice. KEY RESULTS: DSS-induced colitis was significantly exacerbated in B1(-/-) compared with WT mice. IL-1ß, IFN-γ, keratinocyte-derived chemokine and macrophage inflammatory protein-2 were markedly increased in the colon from DSS-treated B1(-/-) compared with DSS-treated WT mice. Treatment of WT mice with a selective B(1) receptor antagonist, DALBK or SSR240612, had no effect on DSS-induced colitis. Of note, B(2) receptor mRNA expression was significantly up-regulated in colonic tissue from the B1(-/-) mice after DSS administration. Moreover, treatment with a selective B(2) receptor antagonist prevented the exacerbation of colitis in B1(-/-) mice following DSS administration. The water- or DSS-treated B1(-/-) mice showed a decrease in occludin gene expression, which was partially prevented by the B(2) receptor antagonist. CONCLUSIONS AND IMPLICATIONS: A loss of B(1) receptors markedly exacerbates the severity of DSS-induced colitis in mice. The increased susceptibility of B1(-/-) may be associated with compensatory overexpression of B(2) receptors, which, in turn, modulates tight junction expression.
Asunto(s)
Colitis/metabolismo , Receptor de Bradiquinina B1/metabolismo , Receptor de Bradiquinina B2/metabolismo , Animales , Bradiquinina/análogos & derivados , Bradiquinina/farmacología , Antagonistas del Receptor de Bradiquinina B1 , Antagonistas del Receptor de Bradiquinina B2 , Colitis/inducido químicamente , Colitis/patología , Citocinas/metabolismo , Sulfato de Dextran , Dioxoles/farmacología , Homeostasis , Mucosa Intestinal/metabolismo , Intestinos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Peroxidasa/metabolismo , Receptor de Bradiquinina B1/genética , Sulfonamidas/farmacología , Uniones Estrechas/metabolismo , Regulación hacia ArribaRESUMEN
The toxicity of amyloid ß (Aß) is highly associated with Alzheimer's disease (AD), which has a high incidence in elderly people worldwide. While the current treatment for moderate and severe AD includes blockage of the N-methyl-d-aspartate receptor (NMDAR), the molecular mechanisms of its effect are still poorly understood. Herein, we report that a single i.p. administration of the selective and competitive (NMDAR) antagonist LY235959 reduced Aß neurotoxicity by preventing the down-regulation of glial glutamate transporters (glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1)), the decrease in glutamate uptake, and the production of reactive oxygen species (ROS) induced by Aß(1-40). Importantly, the blockage of NMDAR restored the Aß(1-40)-induced synaptic dysfunction and cognitive impairment. However, LY235959 failed to prevent the inflammatory response associated with Aß(1-40) treatment. Altogether, our data indicate that the acute administration of Aß promotes oxidative stress, a decrease in glutamate transporter expression, and neurotoxicity. Our results reinforce the idea that NMDAR plays a critical regulatory action in Aß toxicity and they provide further pre-clinical evidence for the potential role of the selective and competitive NMDAR antagonists in the treatment of AD.