SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics

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dc.article.number56
dc.catalogadorpau
dc.contributor.authorPrieto Villalobos, Juan Carlos
dc.contributor.authorLucero, Claudia M.
dc.contributor.authorRovegno, Maximiliano
dc.contributor.authorGómez, Gonzalo I.
dc.contributor.authorRetamal, Mauricio A.
dc.contributor.authorOrellana, Juan A.
dc.date.accessioned2023-10-31T13:32:12Z
dc.date.available2023-10-31T13:32:12Z
dc.date.issued2023
dc.date.updated2023-10-29T00:03:13Z
dc.description.abstractBackground: 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. Results: 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 [Ca2+]i dynamics elicited by ATP. Conclusions: We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.
dc.format.extent14 páginas
dc.identifier.citationBiological Research. 2023 Oct 25;56(1):56
dc.identifier.issn0717-6287
dc.identifier.urihttps://doi.org/10.1186/s40659-023-00468-9
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/75200
dc.information.autorucEscuela de Medicina; Prieto Villalobos, Juan Carlos; S/I; 1071673
dc.information.autorucEscuela de Medicina; Rovegno, Maximiliano; 0000-0002-2882-8024; 1004053
dc.information.autorucEscuela de Medicina; Orellana, Juan A.; 0000-0003-4076-207X; 126007
dc.language.isoen
dc.nota.accesoContenido completo
dc.revistaBiological Research
dc.rightsacceso abierto
dc.rights.holderSociedad de Biologia de Chile
dc.subjectHemichannels
dc.subjectCOVID-19
dc.subjectConnexin 43
dc.subjectSARS-CoV-2
dc.subjectACE2
dc.subjectATP and spike S1
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleSARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics
dc.typeartículo
dc.volumen56
sipa.codpersvinculados1071673
sipa.codpersvinculados1004053
sipa.codpersvinculados126007
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