Universidad del Desarrollo

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SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics
(2023)
Juan Prieto-Villalobos
;
Claudia M. Lucero
;
Maximiliano Rovegno
;
Gonzalo I. Gómez
;
Mauricio A. Retamal
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> dynamics elicited by ATP.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.</jats:p> </jats:sec>
6Scopus© Citations 7
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Connexin Hemichannel Activation by S-Nitrosoglutathione Synergizes Strongly with Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing
(2021)
Chiara Nardin
;
Chiara Peres
;
Sabrina Putti
;
Tiziana Orsini
;
Claudia Colussi
<jats:p>In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca2+) waves propagated from irradiated to bystander cells promoting intracellular Ca2+ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of apoptotic pathways. Combination treatment with S-nitrosoglutathione (GSNO), an endogenous nitric oxide (NO) donor that biases HCs towards the open state, greatly potentiated anti-tumor bystander killing via enhanced Ca2+ signaling, leading to a significant reduction of post-irradiation tumor mass. Our results demonstrate that HCs can be exploited to dramatically increase cytotoxic bystander effects and reveal a previously unappreciated role for HCs in tumor eradication promoted by PDT.</jats:p>
Scopus© Citations 11 1
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Activation of Intra-nodose Ganglion P2X7 Receptors Elicit Increases in Neuronal Activity
(2023)
Julio Alcayaga
;
Jorge Vera
;
Mauricio Reyna-Jeldes
;
Alejandra A. Covarrubias
;
Claudio Coddou
Scopus© Citations 2 2
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Hypertensive Nephropathy: Unveiling the Possible Involvement of Hemichannels and Pannexons
(2022)
Claudia M. Lucero
;
Juan Prieto-Villalobos
;
Lucas Marambio-Ruiz
;
Javiera Balmazabal
;
Tanhia F. Alvear
<jats:p>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.</jats:p>
5Scopus© Citations 18
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Interferon-γ and high glucose-induced opening of Cx43 hemichannels causes endothelial cell dysfunction and damage
(2020)
Juan C. Sáez
;
Susana Contreras-Duarte
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Valeria C. Labra
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Cristian A. Santibañez
;
Luis A. Mellado
Scopus© Citations 30 2
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Editorial: Physiology of Myelin Forming Cells, From Myelination to Neural Modulators
(2019)
Marion Baraban
;
RETAMAL LUCERO, MAURICIO ANTONIO
;
Fernando C. Ortiz
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