scholarly journals Inhibition of telomerase activity alters tight junction protein expression and induces transendothelial migration of HIV-1-infected cells

2010 ◽  
Vol 298 (4) ◽  
pp. H1136-H1145 ◽  
Author(s):  
Wen Huang ◽  
Geun Bae Rha ◽  
Lei Chen ◽  
Melissa J. Seelbach ◽  
Bei Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Transendothelial Migration ◽  
Telomerase Activity ◽  
Brain Endothelial Cells ◽  
Tight Junction Proteins ◽  
Junction Protein ◽  
Infected Cells ◽  
Hiv 1 ◽  
Junction Proteins

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.

scholarly journals Methylglyoxal-Induced Dysfunction in Brain Endothelial Cells via the Suppression of Akt/HIF-1α Pathway and Activation of Mitophagy Associated with Increased Reactive Oxygen Species

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 820 ◽  
Author(s):  
Donghyun Kim ◽  
Kyeong-A Kim ◽  
Jeong-Hyeon Kim ◽  
Eun-Hye Kim ◽  
Ok-Nam Bae
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Tight Junction ◽  
Reactive Oxygen ◽  
Mitochondrial Damage ◽  
Oxygen Species ◽  
Brain Endothelial Cells ◽  
Tight Junction Proteins ◽  
Junction Proteins

Methylglyoxal (MG) is a dicarbonyl compound, the level of which is increased in the blood of diabetes patients. MG is reported to be involved in the development of cerebrovascular complications in diabetes, but the exact mechanisms need to be elucidated. Here, we investigated the possible roles of oxidative stress and mitophagy in MG-induced functional damage in brain endothelial cells (ECs). Treatment of MG significantly altered metabolic stress as observed by the oxygen-consumption rate and barrier-integrity as found in impaired trans-endothelial electrical resistance in brain ECs. The accumulation of MG adducts and the disturbance of the glyoxalase system, which are major detoxification enzymes of MG, occurred concurrently. Reactive oxygen species (ROS)-triggered oxidative damage was observed with increased mitochondrial ROS production and the suppressed Akt/hypoxia-inducible factor 1 alpha (HIF-1α) pathway. Along with the disturbance of mitochondrial bioenergetic function, parkin-1-mediated mitophagy was increased by MG. Treatment of N-acetyl cysteine significantly reversed mitochondrial damage and mitophagy. Notably, MG induced dysregulation of tight junction proteins including occludin, claudin-5, and zonula occluden-1 in brain ECs. Here, we propose that diabetic metabolite MG-associated oxidative stress may contribute to mitochondrial damage and autophagy in brain ECs, resulting in the dysregulation of tight junction proteins and the impairment of permeability.

HIV-1 Tat protein alters tight junction protein expression and distribution in cultured brain endothelial cells

2003 ◽  
Vol 74 (2) ◽  
pp. 255-265 ◽  
Author(s):  
Ibolya E. András ◽  
Hong Pu ◽  
Mária A. Deli ◽  
Avindra Nath ◽  
Bernhard Hennig ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Tight Junction ◽  
Tight Junction Protein ◽  
Brain Endothelial Cells ◽  
Tat Protein ◽  
Tight Junction Protein Expression ◽  
Junction Protein ◽  
Hiv 1

scholarly journals The Tight Junction Proteins Claudin-1, -6, and -9 Are Entry Cofactors for Hepatitis C Virus

2008 ◽  
Vol 82 (7) ◽  
pp. 3555-3560 ◽  
Author(s):  
Laurent Meertens ◽  
Claire Bertaux ◽  
Lisa Cukierman ◽  
Emmanuel Cormier ◽  
Dimitri Lavillette ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Protein ◽  
Cellular Factors ◽  
Cd81 Tetraspanin ◽  
Junction Proteins

ABSTRACT Hepatitis C virus (HCV) is a major cause of liver disease in humans. The CD81 tetraspanin is necessary but not sufficient for HCV penetration into hepatocytes, and it was recently reported that the tight junction protein claudin-1 is a critical HCV entry cofactor. Here, we confirm the role of claudin-1 in HCV entry. In addition, we show that claudin-6 and claudin-9 expressed in CD81+ cells also enable the entry of HCV pseudoparticles derived from six of the major genotypes. Whereas claudin-1, -6, and -9 function equally well as entry cofactors in endothelial cells, claudin-1 is more efficient in hepatoma cells. This suggests that additional cellular factors modulate the ability of claudins to function as HCV entry cofactors. Our work has generated novel and essential means to investigate the mechanism of HCV penetration into hepatocytes and the role of the claudin protein family in HCV dissemination, replication, and pathogenesis.

scholarly journals Regulation of testicular tight junctions by gonadotrophins in the adult Djungarian hamster in vivo

Reproduction ◽  
2008 ◽  
Vol 135 (6) ◽  
pp. 867-877 ◽  
Author(s):  
Gerard A Tarulli ◽  
Sarah J Meachem ◽  
Stefan Schlatt ◽  
Peter G Stanton
Keyword(s):  
Tight Junction ◽  
Adaptor Protein ◽  
Tight Junction Protein ◽  
Mrna Levels ◽  
Tight Junction Proteins ◽  
Djungarian Hamster ◽  
Junction Protein ◽  
Protein Localisation ◽  
Junction Proteins

This study aimed to assess the effect of gonadotrophin suppression and FSH replacement on testicular tight junction dynamics and blood–testis barrier (BTB) organisation in vivo, utilising the seasonal breeding Djungarian hamster. Confocal immunohistology was used to assess the cellular organisation of tight junction proteins and real-time PCR to quantify tight junction mRNA. The effect of tight junction protein organisation on the BTB permeability was also investigated using a biotin-linked tracer. Tight junction protein (claudin-3, junctional adhesion molecule (JAM)-A and occludin) localisation was present but disorganised after gonadotrophin suppression, while mRNA levels (claudin-11, claudin-3 and occludin) were significantly (two- to threefold) increased. By contrast, both protein localisation and mRNA levels for the adaptor protein zona occludens-1 decreased after gonadotrophin suppression. FSH replacement induced a rapid reorganisation of tight junction protein localisation. The functionality of the BTB (as inferred by biotin tracer permeation) was found to be strongly associated with the organisation and localisation of claudin-11. Surprisingly, JAM-A was also recognised on spermatogonia, suggesting an additional novel role for this protein in trans-epithelial migration of germ cells across the BTB. It is concluded that gonadotrophin regulation of tight junction proteins forming the BTB occurs primarily at the level of protein organisation and not gene transcription in this species, and that immunolocalisation of the organised tight junction protein claudin-11 correlates with BTB functionality.

scholarly journals Interleukin-34 Restores Blood–Brain Barrier Integrity by Upregulating Tight Junction Proteins in Endothelial Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115981 ◽  
Author(s):  
Shijie Jin ◽  
Yoshifumi Sonobe ◽  
Jun Kawanokuchi ◽  
Hiroshi Horiuchi ◽  
Yi Cheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Tight Junction Proteins ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity ◽  
Junction Proteins

scholarly journals Decursin Inhibits VEGF-Mediated Inner Blood—Retinal Barrier Breakdown by Suppression of VEGFR-2 Activation

2009 ◽  
Vol 29 (9) ◽  
pp. 1559-1567 ◽  
Author(s):  
Jin Hyoung Kim ◽  
Jeong Hun Kim ◽  
You Mie Lee ◽  
Eun-Mi Ahn ◽  
Kyu-Won Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Vision Loss ◽  
Retinal Vessels ◽  
Tight Junction Proteins ◽  
Blood Retinal Barrier ◽  
Retinal Endothelial Cells ◽  
Extracellular Signal ◽  
Brb Breakdown ◽  
Junction Proteins

The blood—retinal barrier (BRB) is essential for the normal structural and functional integrity of the retina, whose breakdown could cause the serious vision loss. Vascular endothelial growth factor (VEGF), as a permeable factor, induces alteration of tight junction proteins to result in BRB breakdown. Herein, we demonstrated that decursin inhibits VEGF-mediated inner BRB breakdown through suppression of VEGFR-2 signaling pathway. In retinal endothelial cells, decursin inhibited VEGF-mediated hyperpermeability. Decursin prevented VEGF-mediated loss of tight junction proteins including zonula occludens-1 (ZO-1), ZO-2, and occludin in retinal endothelial cells, which was also supported by restoration of tight junction proteins in intercellular junction. In addition, decursin significantly inhibited VEGF-mediated vascular leakage from retinal vessels, which was accompanied by prevention of loss of tight junction proteins in retinal vessels. Decursin significantly suppressed VEGF-induced VEGFR-2 phosphrylation that consequently led to inhibition of extracellular signal-regulated kinase (ERK) 1/2 activation. Moreover, decursin induced no cytotoxicity to retinal endothelial cells and no retinal toxicity under therapeutic concentrations. Therefore, our results suggest that decursin prevents VEGF-mediated BRB breakdown through blocking of loss of tight junction proteins, which might be regulated by suppression of VEGFR-2 activation. As a novel inhibitor to BRB breakdown, decursin could be applied to variable retinopathies with BRB breakdown.

Sign in / Sign up

Export Citation Format

Share Document