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    Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation
    (2021)
    Mauricio A. Lillo
    ;
    Pablo S. Gaete
    ;
    Mariela Puebla
    ;
    Pía C. Burboa
    ;
    Inés Poblete
    <jats:p>Deletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane potential and [Ca2+]i of endothelial cells. Changes in NO-mediated vasodilation, membrane potential, superoxide anion (O2⋅–) formation, and endothelial cell [Ca2+]i were analyzed in rat isolated mesenteric arterial beds and primary cultures of mesenteric endothelial cells. Inhibition of Panx-1 channels with probenecid (1 mM) or the Panx-1 blocking peptide 10Panx (60 μM) evoked an increase in the ACh (100 nM)-induced vasodilation of KCl-contracted mesenteries and in the phosphorylation level of endothelial NO synthase (eNOS) at serine 1177 (P-eNOSS1177) and Akt at serine 473 (P-AktS473). In addition, probenecid or 10Panx application activated a rapid, tetrodotoxin (TTX, 300 nM)-sensitive, membrane potential depolarization and [Ca2+]i increase in endothelial cells. Interestingly, the endothelial cell depolarization was converted into a transient spike after removing Ca2+ ions from the buffer solution and in the presence of 100 μM mibefradil or 10 μM Ni2+. As expected, Ni2+ also abolished the increment in [Ca2+]i. Expression of Nav1.2, Nav1.6, and Cav3.2 isoforms of voltage-dependent Na+ and Ca2+ channels was confirmed by immunocytochemistry. Furthermore, the Panx-1 channel blockade was associated with an increase in O2⋅– production. Treatment with 10 μM TEMPOL or 100 μM apocynin prevented the increase in O2⋅– formation, ACh-induced vasodilation, P-eNOSS1177, and P-AktS473 observed in response to Panx-1 inhibition. These findings indicate that the Panx-1 channel blockade triggers a novel complex signaling pathway initiated by the sequential activation of TTX-sensitive Nav channels and Cav3.2 channels, leading to an increase in NO-mediated vasodilation through a NADPH oxidase-dependent P-eNOSS1177, which suggests that Panx-1 may be involved in the endothelium-dependent control of arterial blood pressure.</jats:p>
      7Scopus© Citations 16
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    Multidimensional inhibitory signatures of sentential negation in behavioral variant frontotemporal dementia
    (2022)
    Mariano N Díaz-Rivera
    ;
    Agustina Birba
    ;
    Sol Fittipaldi
    ;
    Débora Mola
    ;
    Yurena Morera
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Processing of linguistic negation has been associated to inhibitory brain mechanisms. However, no study has tapped this link via multimodal measures in patients with core inhibitory alterations, a critical approach to reveal direct neural correlates and potential disease markers.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Here we examined oscillatory, neuroanatomical, and functional connectivity signatures of a recently reported Go/No-go negation task in healthy controls and behavioral variant frontotemporal dementia (bvFTD) patients, typified by primary and generalized inhibitory disruptions. To test for specificity, we also recruited persons with Alzheimer's disease (AD), a disease involving frequent but nonprimary inhibitory deficits.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In controls, negative sentences in the No-go condition distinctly involved frontocentral delta (2–3 Hz) suppression, a canonical inhibitory marker. In bvFTD patients, this modulation was selectively abolished and significantly correlated with the volume and functional connectivity of regions supporting inhibition (e.g. precentral gyrus, caudate nucleus, and cerebellum). Such canonical delta suppression was preserved in the AD group and associated with widespread anatomo-functional patterns across non-inhibitory regions.</jats:p> </jats:sec> <jats:sec> <jats:title>Discussion</jats:title> <jats:p>These findings suggest that negation hinges on the integrity and interaction of spatiotemporal inhibitory mechanisms. Moreover, our results reveal potential neurocognitive markers of bvFTD, opening a new agenda at the crossing of cognitive neuroscience and behavioral neurology.</jats:p> </jats:sec>
    Scopus© Citations 18  4
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    Scopus© Citations 22  2
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      12Scopus© Citations 3
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    Concordance Analysis of ALK Gene Fusion Detection Methods in Patients with Non–Small-Cell Lung Cancer from Chile, Brazil, and Peru
    (2021)
    Gonzalo Sepúlveda-Hermosilla
    ;
    Matías Freire
    ;
    Alejandro Blanco
    ;
    Javier Cáceres
    ;
    Rodrigo Lizana
      1Scopus© Citations 6
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      13Scopus© Citations 4
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    Receptors involved in dexketoprofen analgesia in murine visceral pain
    (2020)
    V Noriega
    ;
    F Sierralta
    ;
    P Poblete
    ;
    N Aranda
    ;
    R Sotomayor-Zárate
      52Scopus© Citations 2
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    Scopus© Citations 8  3
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    Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer
    (2015)
    Iván Roa
    ;
    Gonzalo de Toro
    ;
    Fernanda Fernández
    ;
    Anakaren Game
    ;
    Sergio Muñoz
    Scopus© Citations 22  2