HIV increases the release of dickkopf-1 protein from human astrocytes by a Cx43 hemichannel-dependent mechanism.

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dc.catalogadorpva
dc.contributor.authorOrellana Roca, Juan Andrés
dc.contributor.authorSáez, Juan Carlos
dc.contributor.authorLann Bennett, Michael Vander
dc.contributor.authorWeinberger Berman, Joan
dc.contributor.authorMorgello, Susan
dc.contributor.authorEugenín Arce, Eliseo Alberto
dc.date.accessioned2016-05-10T18:11:17Z
dc.date.available2016-05-10T18:11:17Z
dc.date.issued2014
dc.description.abstractHuman immunodeficiency virus-1 (HIV) is a public health issue and a major complication of the disease is NeuroAIDS. In vivo, microglia/macrophages are the main cells infected. However, a low but significant number of HIV-infected astrocytes has also been detected, but their role in the pathogenesis of NeuroAIDS is not well understood. Our previous data indicate that gap junction channels amplify toxicity from few HIV-infected into uninfected astrocytes. Now, we demonstrated that HIV infection of astrocytes results in the opening of connexin43 hemichannels (HCs). HIV-induced opening of connexin43 HCs resulted in dysregulated secretion of dickkopf-1 protein (DKK1, a soluble wnt pathway inhibitor). Treatment of mixed cultures of neurons and astrocytes with DKK1, in the absence of HIV infection, resulted in the collapse of neuronal processes. HIV infection of mixed cultures of human neurons and astrocytes also resulted in the collapse of neuronal processes through a DKK1-dependent mechanism. In addition, dysregulated DKK1 expression in astrocytes was observed in human brain tissue sections of individuals with HIV encephalitis as compared to tissue sections from uninfected individuals. Thus, we demonstrated that HIV infection of astrocytes induces dysregulation of DKK1 by a HC-dependent mechanism that contributes to the brain pathogenesis observed in HIV-infected individuals.", "Our studies demonstrated that HIV infection of astrocytes, despite minimal replication and a low number of infected cells, induces dysregulation of DKK1 secretion by a Cx43 hemichannel (HC)-dependent mechanism. Enhanced DKK1 secretion in response to HIV infection of glial cells compromised formation and stability of neuronal processes, similar to the synaptic compromise observed in HIV-infected individuals. In addition, analysis of human brain tissue sections obtained from encephalitic individuals also shows enhanced expression of DKK1 in astrocytes. Our data provide a novel mechanism by which HIV infection of glial cells participate in the pathogenesis of brain dysfunction observed in HIV-infected individuals. LRP5=Low-density lipoprotein receptor-related protein 5.
dc.fechaingreso.objetodigital2025-06-02
dc.identifier.doi10.1111/jnc.12492
dc.identifier.issn0022-3042
dc.identifier.urihttps://doi.org/10.1111/jnc.12492
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/13210
dc.identifier.wosidWOS:000331551600013
dc.information.autorucFacultad de Ciencias Biológicas; Orellana Roca, Juan Andrés; 0000-0003-4076-207X; 126007
dc.information.autorucFacultad de Ciencias Biológicas; Sáez, Juan Carlos; 0000-0003-3811-0347; 99913
dc.information.autorucFacultad de Ciencias Biológicas; Eugenín Arce, Eliseo Alberto; S/I; 6246
dc.issue.numeroNo. 5
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final763
dc.pagina.inicio752
dc.publisherJohn Wiley & Sons
dc.relation.isformatofJournal of Neurochemistry Vol. 128, No. 5, p. 752-763.
dc.revistaJournal of Neurochemistryes_ES
dc.rightsacceso restringido
dc.solicitanteGap junctions
dc.subjectHIV
dc.subjectDementia
dc.subjectNeuroAIDS
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.subject.otherSIDA - Patologíaes_ES
dc.subject.otherInfecciones por VIHes_ES
dc.subject.otherDemenciaes_ES
dc.subject.otherAstrocitos - Virologíaes_ES
dc.subject.otherProteínas Wntes_ES
dc.titleHIV increases the release of dickkopf-1 protein from human astrocytes by a Cx43 hemichannel-dependent mechanism.es_ES
dc.typeartículo
dc.volumenVol. 128
sipa.codpersvinculados99913
sipa.codpersvinculados126007
sipa.codpersvinculados6246
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