Browsing by Author "Alvear Soto, Tanhia Francheska"

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    Hypertensive Nephropathy: Unveiling the Possible Involvement of Hemichannels and Pannexons
    (2022) Lucero, Claudia M.; Prieto Villalobos, Juan Carlos; Marambio-Ruiz, Lucas; Balmazabal, Javiera; Alvear Soto, Tanhia Francheska; Vega, Matías; Barra, Paola; Retamal, Mauricio A.; Orellana Roca, Juan Andrés; Gómez, Gonzalo I.
    Hypertension is one of the most common risk factors for developing chronic cardiovascular diseases, including hypertensive nephropathy. Within the glomerulus, hypertension causes damage and activation of mesangial cells (MCs), eliciting the production of large amounts of vasoactive and proinflammatory agents. Accordingly, the activation of AT1 receptors by the vasoactive molecule angiotensin II (AngII) contributes to the pathogenesis of renal damage, which is mediated mostly by the dysfunction of intracellular Ca2+ ([Ca2+]i) signaling. Similarly, inflammation entails complex processes, where [Ca2+]i also play crucial roles. Deregulation of this second messenger increases cell damage and promotes fibrosis, reduces renal blood flow, and impairs the glomerular filtration barrier. In vertebrates, [Ca2+]i signaling depends, in part, on the activity of two families of large-pore channels: hemichannels and pannexons. Interestingly, the opening of these channels depends on [Ca2+]i signaling. In this review, we propose that the opening of channels formed by connexins and/or pannexins mediated by AngII induces the ATP release to the extracellular media, with the subsequent activation of purinergic receptors. This process could elicit Ca2+ overload and constitute a feed-forward mechanism, leading to kidney damage.
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    The Opening of Connexin 43 Hemichannels Alters Hippocampal Astrocyte Function and Neuronal Survival in Prenatally LPS-Exposed Adult Offspring
    (2019) Chávez Chaname, Carolina Elizabeth; Oyarzún Isamitt, Juan Esteban; Avendaño, Beatriz C.; Mellado, Luis A.; Inostroza, Carla A.; Alvear Soto, Tanhia Francheska; Orellana Roca, Juan Andrés
    Clinical evidence has revealed that children born from mothers exposed to viral and bacterial pathogens during pregnancy are more likely to suffer various neurological disorders including schizophrenia, autism bipolar disorder, major depression, epilepsy, and cerebral palsy. Despite that most research has centered on the impact of prenatal inflammation in neurons and microglia, the potential modifications of astrocytes and neuron-astrocyte communication have received less scrutiny. Here, we evaluated whether prenatally LPS-exposed offspring display alterations in the opening of astrocyte hemichannels and pannexons in the hippocampus, together with changes in neuroinflammation, intracellular Ca2+ and nitric oxide (NO) signaling, gliotransmitter release, cell arborization, and neuronal survival. Ethidium uptake recordings revealed that prenatal LPS exposure enhances the opening of astrocyte Cx43 hemichannels and Panx1 channels in the hippocampus of adult offspring mice. This enhanced channel activity occurred by a mechanism involving a microglia-dependent production of IL-1 beta/TNF-alpha and the stimulation of p38 MAP kinase/iNOS/[Ca2+](i)-mediated signaling and purinergic/glutamatergic pathways. Noteworthy, the activity of Cx43 hemichannels affected the release of glutamate, [Ca2+](i) handling, and morphology of astrocytes, whereas also disturbed neuronal function, including the dendritic arbor and spine density, as well as survival. We speculate that excitotoxic levels of glutamate triggered by the activation of Cx43 hemichannels may contribute to hippocampal neurotoxicity and damage in prenatally LPS-exposed offspring. Therefore, the understanding of how astrocyte-neuron crosstalk is an auspicious avenue toward the development of broad treatments for several neurological disorders observed in children born to women who had a severe infection during gestation.