Browsing by Author "Giaume, Christian"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Hemichannels Are Required for Amyloid β-Peptide-Induced Degranulation and Are Activated in Brain Mast Cells of APPswe/PS1dE9 Mice
    (2015) Harcha, Paloma A.; Vargas, Aníbal; Yi, Chenju; Koulakoff, Annette A.; Giaume, Christian; Sáez, Juan Carlos
  • No Thumbnail Available
    Item
    Impact of Microglial Activation on Astroglial Connexin Expression and Function in Brain Inflammation
    (Taylor and Francis publisher, 2013) Giaume, Christian; Froger, Nicolás; Orellana Roca, Juan Andrés; Retamal Lucero, Mauricio Antonio; Saéz Carreño, Juan Carlos
    The central nervous system (CNS) is capable of dynamic immune and inŽammatory responses mediated by the activation of microglia, the brain resident macrophage population, and astrocyte reactivity. A growing body of evidence shows that the innate immune response exerts a dichotomous role in the brain. Under physiological conditions, microglia exhibit a resting phenotype that is associated with the production of anti-inŽammatory and neurotrophic factors. Microglia shift to an activated phenotype in response to a wide range of insults that activate speciŸc signaling pathways, thereby promoting an inŽammatory response necessary to further engage the immune system. The sustained inŽammation resulting in brain injury and pathology
  • No Thumbnail Available
    Item
    Modulation of Brain Hemichannels and Gap Junction Channels by Pro-Inflammatory Agents and Their Possible Role in Neurodegeneration
    (Mary Ann Liebert, 2009) Orellana Roca, Juan Andrés; Sáez Pedraza, Pablo José; Shoji Sánchez, Kenji Fabricio; Schalper Casanova, Kurt Alex; Palacios Prado, Nicolás; Velarde Aliaga, María Victoria; Giaume, Christian; Bennett, Michael V. L.; Sáez, Juan Carlos
    In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra-and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e. g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process. Antiox. Redox Signal. 11, 369-399.
  • Thumbnail Image
    Item
    Permeation of molecules through astroglial connexin 43 hemichannels is modulated by cytokines with parameters depending on the permeant species
    (2020) Sáez, Juan Carlos; Vargas, Aníbal A.; Hernández, Diego E.; Ortiz, Fernando C.; Giaume, Christian; Orellana Roca, Juan Andrés
    Recent studies indicate that connexin hemichannels do not act as freely permeable non-selective pores, but they select permeants in an isoform-specific manner with cooperative, competitive and saturable kinetics. The aim of this study was to investigate whether the treatment with a mixture of IL-1 beta plus TNF-alpha, a well-known pro-inflammatory condition that activates astroglial connexin 43 (Cx43) hemichannels, could alter their permeability to molecules. We found that IL-1 beta plus TNF-alpha left-shifted the dye uptake rate vs. dye concentration relationship for Etd and 2-NBDG, but the opposite took place for DAPI or YO-PRO-1, whereas no alterations were observed for Prd. The latter modifications were accompanied of changes in K-d (Etd, DAPI, YO-PRO-1 or 2-NBDG) and Hill coefficients (Etd and YO-PRO-1), but not in alterations of V-max. We speculate that IL-1 beta plus TNF-alpha may distinctively affect the binding sites to permeants in astroglial Cx43 hemichannels rather than their number in the cell surface. Alternatively, IL-1 beta plus TNF-alpha could induce the production of endogenous permeants that may favor or compete for in the pore-lining residues of Cx43 hemichannels. Future studies shall elucidate whether the differential ionic/molecule permeation of Cx43 hemichannels in astrocytes could impact their communication with neurons in the normal and inflamed nervous system.
  • Thumbnail Image
    Item
    Role of Connexin Hemichannels in Neurodegeneration
    (InTech, 2011) Orellana Roca, Juan Andrés; Sáez, Juan Carlos; Giaume, Christian