scholarly journals Inhibition of telomerase activity contributes to HIV‐1‐induced activation of inflammatory responses and alteration of tight junction protein expression in human brain endothelial cells

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Wen Huang ◽  
Ibolya E. András ◽  
Sung Yong Eum ◽  
Bernhard Hennig ◽  
Michal Toborek
2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Wen Huang ◽  
Ibolya E András ◽  
Sung Yong Eum ◽  
Yu Zhong ◽  
Pierre‐Olivier Couraud ◽  
...  

2003 ◽  
Vol 74 (2) ◽  
pp. 255-265 ◽  
Author(s):  
Ibolya E. András ◽  
Hong Pu ◽  
Mária A. Deli ◽  
Avindra Nath ◽  
Bernhard Hennig ◽  
...  

2010 ◽  
Vol 298 (4) ◽  
pp. H1136-H1145 ◽  
Author(s):  
Wen Huang ◽  
Geun Bae Rha ◽  
Lei Chen ◽  
Melissa J. Seelbach ◽  
Bei Zhang ◽  
...  

Telomerase, via its catalytic component telomerase reverse transcriptase (TERT), extends telomeres of eukaryotic chromosomes. The importance of this reaction is related to the fact that telomere shortening is a rate-limiting mechanism for human life span that induces cell senescence and contributes to the development of age-related pathologies. The aim of the present study was to evaluate whether the modulation of telomerase activity can influence human immunodeficiency virus type 1 (HIV-1)-mediated dysfunction of human brain endothelial cells (hCMEC/D3 cells) and transendothelial migration of HIV-1-infected cells. Telomerase activity was modulated in hCMEC/D3 cells via small interfering RNA-targeting human TERT (hTERT) or by using a specific pharmacological inhibitor of telomerase, TAG-6. The inhibition of hTERT resulted in the upregulation of HIV-1-induced overexpression of intercellular adhesion molecule-1 via the nuclear factor-κB-regulated mechanism and induced the transendothelial migration of HIV-1-infected monocytic U937 cells. In addition, the blocking of hTERT activity potentiated a HIV-induced downregulation of the expression of tight junction proteins. These results were confirmed in TERT-deficient mice injected with HIV-1-specific protein Tat into the cerebral vasculature. Further studies revealed that the upregulation of matrix metalloproteinase-9 is the underlying mechanisms of disruption of tight junction proteins in hCMEC/D3 cells with inhibited TERT and exposed to HIV-1. These results indicate that the senescence of brain endothelial cells may predispose to the HIV-induced upregulation of inflammatory mediators and the disruption of the barrier function at the level of the brain endothelium.


1996 ◽  
Vol 320 (3) ◽  
pp. 717-721 ◽  
Author(s):  
Thomas W. GARDNER ◽  
Treena LESHER ◽  
Sonny KHIN ◽  
Cuong VU ◽  
Alistair J. BARBER ◽  
...  

We examined ZO-1 protein content in cultured retinal vascular endothelial cells to test the hypothesis that histamine alters tight-junction-protein expression. Histamine (10-9 –10-4 M) causes a reversible concentration-dependent reduction of ZO-1 protein content, mediated by both H1 and H2 receptors. Histamine reduces ZO-1 expression within the time associated with increased paracellular permeability. Tight-junction-protein alterations may be a novel explanation for the mechanism by which vasoactive agents increase microvascular permeability.


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