This research provides evidence that human periodontal ligament, in addition to its mesodermal derivatives, produces neural crest-like cells. Such features suggest a recapitulation of their embryonic state. The human periodontal ligament revealed itself as a viable alternative source for possible primitive precursors to be used in stem-cell therapies.
New unconventional approaches to the development of antimicrobial drugs must target inhibition of infection stages leading to host colonisation or virulence itself, rather than bacterial viability. Amongst the most promising unconventional targets for the development of new antimicrobial drugs is bacterial adherence and biofilm formation as well as their control system, the quorum-sensing (QS) system, a mechanism of communication used to co-ordinate bacterial activities. Here we describe the evaluation of synthetic organic compounds as bacterial biofilm inhibitors against a panel of clinically relevant Gram-positive and Gram-negative bacterial strains. This approach has successfully allowed the identification of five compounds (GEt, GHex, GOctad, G19 and C33) active not only against bacterial biofilms but also displaying potential to be used as antagonists and/or inhibitors of bacterial QS.
Proteoglycans are considered to be important molecule in cell-microenvironment interactions. They are overexpressed in neoplastic cells modifying their growth and migration in hosts. In this work we verified that undersulfation of proteoglycans and other sulfated molecules, induced by sodium chlorate treatment, inhibited C6 glioma cells proliferation in a dose-dependent way. This effect was restored by the addition of exogenous heparin. We could not detect significant cell mortality in our culture condition. The treatment also impaired in a dose-dependent manner, C6 cell adhesion to extracellular matrix (ECM) proteins (collagen IV, laminin and fibronectin). In addition, sodium chlorate treatment altered C6 glioma cell morphology, from the fibroblast-like to a more rounded one. This effect was accompanied by increased synthesis of fibronectin and alterations in its extracellular network organization. However, we could not observe modifications on laminin organization and synthesis. The results suggest an important connection between sulfation degree with important tumor functions, such as proliferation and adhesion. We suggest that proteoglycans may modulate the glioma microenvironment network during tumor cell progression and invasion.
Pb(II) is a neurotoxic pollutant that produces permanent cognitive deficits in children. Pb(II) can modulate cell signaling pathways and cell viability in a variety of cell types. However, these actions are not well demonstrated on glial cells, which represent an important target for metals into the central nervous system. The present work was undertaken to determine the ability of Pb(II) in modulating the activity of mitogen activated protein kinases (MAPKs) in cultures of C6 rat glioma cells, a useful functional model for the study of astrocytes. Additionally, cell viability was analyzed by measurement of MTT reduction. Cells were exposed to lead acetate 0.1, 1, 10 microM for 24 and 48 h. MAPKs activation - in particular ERK1/2, p38(MAPK) and JNK1/2 - were analyzed by western blotting. Results showed that 10 microM Pb(II) treatment for 24 h caused a discrete stimulation of p38(MAPK) phosphorylation. However, 1 and 10 microM Pb(II) treatment for 48 h provoked a significant stimulation in the phosphorylation state of p38(MAPK) and JNK1/2. The phosphorylation state of ERK1/2 was not modified by any Pb(II) treatment. Moreover, data indicate that at 48 h treatment even 1 microM Pb(II) can be cytotoxic, causing impairment on cell viability. Therefore, depending on a long incubation period, a significant concomitant activation of p38(MAPK) and JNK1/2 by Pb(II) took place in parallel with the impairment of C6 glioma cells viability.
The effects of thyroid hormone (T(3)) on extracellular matrix (ECM) expression and organization in cerebellar astrocytes were studied. Control astrocytes exhibit laminin immunostaining distributed in a punctate configuration and fibronectin concentrated in focal points at the cell surface. These cells attach to the substratum by membrane points, as shown by scanning microscopy, possibly by focal points stained to fibronectin. In contrast, after T(3) treatment, laminin assumes a fibrillary pattern and fibronectin becomes organized in filaments homogeneously distributed on the cell surface; the cells acquire a very flat and spread morphology. T(3) treatment also modulates astrocyte adhesion. In addition, increased expression of both laminin and fibronectin was detected by Western blot. These alterations in fibronectin and/or laminin production and organization may be involved in the flat and spread morphology and in altered adhesion. We observed that fibroblast growth factor-2 (FGF(2)) added to cultures had similar effects to those described to T(3). Neutralizing antibodies against FGF(2) reversed T(3) effects on fibronectin and laminin distribution. We also observed that cerebellar neurons co-cultured on T(3)-treated astrocytes had an increase in the number of cells and presented longer neurites. Thus, we propose a novel mechanism of the effect of thyroid hormone on cerebellar development mediated by astrocytes: T(3) may induce astrocyte secretion of growth factors, mainly FGF(2), that autocrinally stimulate astrocyte proliferation, reorganization in ECM proteins, and alterations in cell spreading and adhesion. These effects may indirectly influence neuronal development.
BackgroundAdhesion to extracellular matrix (ECM) components has been implicated in the proliferative and invasive properties of tumor cells. We investigated the ability of C6 glioma cells to attach to ECM components in vitro and described the regulatory role of glycosaminoglycans (GAGs) on their adhesion to the substrate, proliferation and migration.ResultsECM proteins (type IV collagen, laminin and fibronectin) stimulate rat C6 glioma cell line adhesion in vitro, in a dose-dependent manner. The higher adhesion values were achieved with type IV collagen. Exogenous heparin or chondroitin sulfate impaired, in a dose-dependent manner the attachment of C6 glioma cell line to laminin and fibronectin, but not to type IV collagen. Dextran sulfate did not affect C6 adhesion to any ECM protein analyzed, indicating a specific role of GAGs in mediating glioma adhesion to laminin and fibronectin. GAGs and dextran sulfate did not induce C6 glioma detachment from any tested substrate suggesting specific effect in the initial step of cell adhesion. Furthermore, heparin and chondroitin sulfate impaired C6 cells proliferation on fibronectin, but not on type IV collagen or laminin. In contrast, both GAGs stimulate the glioma migration on laminin without effect on type IV collagen or fibronectin.ConclusionThe results suggest that GAGs and proteoglycans regulate glioma cell adhesion to ECM proteins in specific manner leading to cell proliferation or cell migration, according to the ECM composition, thus modulating tumor cell properties.
synaptic enrichment of AMPARs, in the absence of 2B, is a cell autonomous phenomenon.Focal application of glutamate (100 M), in conjunction with voltage clamp recordings, showed suppression of NMDAR responses in 2B null cultures up to 16 DIV (90% suppression at 14-16DIV). However, pharmacological analysis of wildtype neurons at this age showed a significant contribution of the NMDAR response was due to 2A subunits (58-86%). This demonstrates the requirement for 2B signaling in subsequent expression of functional NR2A containing surface receptors.These studies reveal two important yet distinct roles for the NR2B protein in regulating cortical synapse maturation; first, NR2B expression regulates insertion of AMPARs at synapses, and second, expression of NR2B protein is required for the subsequent functional insertion of NR2A containing receptors at the neuronal membrane.T 3 is essential to central nervous system development. T 3 deficiency during the neonatal period impairs growth and differentiation of glial cells and neurons, resulting in severe mental and physical retardation, known in humans as cretinism. Extracellular matrix (ECM) proteins, such as laminin (LN) and fibronectin (FN), are involved in cellular differentiation, proliferation, migration and adhesion. Neuron-glia interactions have fundamental importance in the organization and maintenance of nervous system architecture. In the present study, we analyzed the T 3 effects on ECM expression in astrocytes from newborn rat cerebellum. We observed a punctate pattern of LN immunoreactivity in control astrocyte cultures while in T 3 -treated astrocytes it showed a fibrillar configuration. FN reactivity was concentrated in focal points in control cells and became uniformly dispersed on the cell surface of T 3 -treated astrocytes. These effects of T 3 in the ECM proteins organization were mediated by fibroblast growth factor-2 (FGF 2 ), because neutralizing antibodies anti-FGF 2 prevent the LN and FN reorganization in T 3 -treated astrocytes. Western blot analysis showed increase of laminin and fibronectin production. Astrocytes from hypothyroid animals exhibited a marked reduction the LN and FN immunoreactivity both by immunofluorescence and by western blot. We also investigated neuronal growth and neuritogenesis. Neurons co-cultured on T 3 -treated astrocytes, displayed longer neurites than that co-cultured on control astrocytes. In addition, hypothyroid neurons co-cultured on normal astrocytes were presented in larger number and displayed longer neurites than when co-cultured on hypothyroids astrocytes. Otherwise, we observed reduction in the number of normal neurons that displayed short neurites when co-cultured on hypothyroid astrocytes. We propose a new mechanism of T 3 effects on cerebellar development mediated by astrocytes: T 3 may induce the astrocyte secretion of FGF 2 that autocrinally induce the reorganization of ECM proteins. These effects can indirectly influence the neuronal development. Acknowledgement
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