Abstract
Background and Aims: Increased amyloid deposition in HIV-infected brains may contribute to the pathogenesis of neurocognitive dysfunction in infected patients. We have previously shown that exposure to HIV results in enhanced amyloid β (Aβ) levels in human brain microvascular endothelial cells, suggesting that brain endothelial cells contribute to accumulation of Aβ in HIV-infected brains. Importantly, Aβ not only accumulates in the cytoplasm of HIV-exposed cells but also enters the nuclei of brain endothelial cells. Methods: cDNA microarray analysis was performed in order to examine changes in the transcriptional profile associated with Aβ nuclear entry in the presence of HIV-1. Results: Gene network analysis indicated that inhibition of nuclear entry of Aβ resulted in enrichment in gene sets involved in apoptosis and survival, endoplasmic reticulum stress response, immune response, cell cycle, DNA damage, oxidative stress, cytoskeleton remodeling and transforming growth factor β (TGFβ) receptor signaling. Conclusions: The obtained data indicate that HIV-induced Aβ nuclear uptake affects several cellular stress-related pathways relevant for HIV-induced Aβ pathology.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 744-752 |
| Number of pages | 9 |
| Journal | Archives of Medical Research |
| Volume | 45 |
| Issue number | 8 |
| DOIs | |
| State | Published - Nov 1 2014 |
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Keywords
- Amyloid beta
- Blood-brain barrier
- DNA microarray
- HIV
ASJC Scopus subject areas
- Medicine(all)
Cite this
Transcriptional Profile of HIV-induced Nuclear Translocation of Amyloid β in Brain Endothelial Cells. / Andras, Ibolya Edit; Rampersaud, Evadnie; Eum, Sung Yong; Toborek, Michal J.
In: Archives of Medical Research, Vol. 45, No. 8, 01.11.2014, p. 744-752.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transcriptional Profile of HIV-induced Nuclear Translocation of Amyloid β in Brain Endothelial Cells
AU - Andras, Ibolya Edit
AU - Rampersaud, Evadnie
AU - Eum, Sung Yong
AU - Toborek, Michal J
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Background and Aims: Increased amyloid deposition in HIV-infected brains may contribute to the pathogenesis of neurocognitive dysfunction in infected patients. We have previously shown that exposure to HIV results in enhanced amyloid β (Aβ) levels in human brain microvascular endothelial cells, suggesting that brain endothelial cells contribute to accumulation of Aβ in HIV-infected brains. Importantly, Aβ not only accumulates in the cytoplasm of HIV-exposed cells but also enters the nuclei of brain endothelial cells. Methods: cDNA microarray analysis was performed in order to examine changes in the transcriptional profile associated with Aβ nuclear entry in the presence of HIV-1. Results: Gene network analysis indicated that inhibition of nuclear entry of Aβ resulted in enrichment in gene sets involved in apoptosis and survival, endoplasmic reticulum stress response, immune response, cell cycle, DNA damage, oxidative stress, cytoskeleton remodeling and transforming growth factor β (TGFβ) receptor signaling. Conclusions: The obtained data indicate that HIV-induced Aβ nuclear uptake affects several cellular stress-related pathways relevant for HIV-induced Aβ pathology.
AB - Background and Aims: Increased amyloid deposition in HIV-infected brains may contribute to the pathogenesis of neurocognitive dysfunction in infected patients. We have previously shown that exposure to HIV results in enhanced amyloid β (Aβ) levels in human brain microvascular endothelial cells, suggesting that brain endothelial cells contribute to accumulation of Aβ in HIV-infected brains. Importantly, Aβ not only accumulates in the cytoplasm of HIV-exposed cells but also enters the nuclei of brain endothelial cells. Methods: cDNA microarray analysis was performed in order to examine changes in the transcriptional profile associated with Aβ nuclear entry in the presence of HIV-1. Results: Gene network analysis indicated that inhibition of nuclear entry of Aβ resulted in enrichment in gene sets involved in apoptosis and survival, endoplasmic reticulum stress response, immune response, cell cycle, DNA damage, oxidative stress, cytoskeleton remodeling and transforming growth factor β (TGFβ) receptor signaling. Conclusions: The obtained data indicate that HIV-induced Aβ nuclear uptake affects several cellular stress-related pathways relevant for HIV-induced Aβ pathology.
KW - Amyloid beta
KW - Blood-brain barrier
KW - DNA microarray
KW - HIV
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U2 - 10.1016/j.arcmed.2014.11.003
DO - 10.1016/j.arcmed.2014.11.003
M3 - Article
VL - 45
SP - 744
EP - 752
JO - Archives of Medical Research
JF - Archives of Medical Research
SN - 0188-4409
IS - 8
ER -