HIV increases the release of dickkopf-1 protein from human astrocytes by a Cx43 hemichannel-dependent mechanism.
HIV increases the release of dickkopf-1 protein from human astrocytes by a Cx43 hemichannel-dependent mechanism.
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DOI:
10.1111/jnc.12492
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发表时间:
2014-03
影响因子:
4.7
通讯作者:
Eugenin EA
中科院分区:
文献类型:
--
作者:
Orellana JA;Sáez JC;Bennett MV;Berman JW;Morgello S;Eugenin EA
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 also has been detected, but their role in the pathogenesis of NeuroAIDS is not well understood. Our previous data indicates that gap junction channels amplify toxicity from few HIV infected into uninfected astrocytes. Now, we demonstrated that HIV infection of astrocytes results in opening of connexin43 hemichannels (Cx43 HCs). HIV induced opening of Cx43 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 collapse of neuronal processes. HIV infection of mixed cultures of human neurons and astrocytes also resulted in collapse of neuronal processes by 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.
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影响因子:
5.3
作者:
Chen Y;Andres AL;Frotscher M;Baram TZ
通讯作者:
Baram TZ
DOI:
10.1016/s0960-5428(06)80269-x
发表时间:
1994-01-01
期刊:
ADVANCES IN NEUROIMMUNOLOGY
影响因子:
--
作者:
CONANT, K;TORNATORE, C;MAJOR, EO
通讯作者:
MAJOR, EO
DOI:
10.1073/pnas.0611699104
发表时间:
2007-02-27
影响因子:
11.1
作者:
Eugenin, Eliseo A.;King, Jessie E.;Berman, Joan W.
通讯作者:
Berman, Joan W.
影响因子:
12.7
作者:
An, SF;Groves, M;Scaravilli, F
通讯作者:
Scaravilli, F
影响因子:
--
作者:
Du, W. J.;Li, J. K.;Yu, B.
通讯作者:
Yu, B.