Browsing by Author "Eugenín Arce, Eliseo Alberto"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    HIV increases the release of dickkopf-1 protein from human astrocytes by a Cx43 hemichannel-dependent mechanism.
    (John Wiley & Sons, 2014) Orellana Roca, Juan Andrés; Sáez, Juan Carlos; Lann Bennett, Michael Vander; Weinberger Berman, Joan; Morgello, Susan; Eugenín Arce, Eliseo Alberto
    Human 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.
  • No Thumbnail Available
    Item
    HIV infection of astrocytes increases release of Dickkopf-1 protein by a gap junction and hemichannel dependent mechanism
    (Springer, 2012) Orellana Roca, Juan Andrés; Sáez, Juan Carlos; Berman, Joan; Eugenín Arce, Eliseo Alberto
    Human immunodeficiency virus-1 (HIV) is a major public health issue, with a significant CNS complication of infection, NeuroAIDS. In vivo, microglia/macrophages are the main cells infected. However, a low but significant number of HIV infected astrocytes also has been detected, but their role in the pathogenesis of NeuroAIDS is not well understood. Our previous data indicated that HIV infection of astrocytes increased expression of the glycoprotein, dickkopf-1 protein (Dkk1), a soluble inhibitor of the wnt pathway. In HIV infected cultures of human astrocytes, secretion of Dkk1 was highly regulated by functional gap junction channels and connexin43 hemichannels. We also demonstrated that Dkk1 expression in astrocytes was increased in human brain tissue sections of individuals with HIV encephalitis as compared to tissue sections from uninfected individuals. We demonstrated that in primary cells, Dkk1 secretion did not participate in bystander killing of uninfected astrocytes or viral reactivation. However, its secretion regulates neuronal damage measured by collapse of neuronal processes. Thus, we demonstrated that HIV infection of astrocytes dysregulates secretion of Dkk1 by a mechanisms that involves both gap junctions as well as hemichannels that contributes to the neuropathogenesis observed in HIV infected individuals.
  • No Thumbnail Available
    Item
    SDF-1/CXCL12 induces migration of lymphocytes by a mechanism pannexin1 hemichannel dependent
    (AMER SOC CELL BIOLOGY, 2012) Velásquez, Stephani; Orellana Roca, Juan Andrés; Sáez, Juan Carlos; Eugenín Arce, Eliseo Alberto
  • Thumbnail Image
    Item
    The role of gap junction channels during physiologic and pathologic conditions of the human central nervous system
    (2012) Eugenín Arce, Eliseo Alberto; Sáez, Juan Carlos; Orellana Roca, Juan Andrés
  • Thumbnail Image
    Item