scholarly journals Rho signaling is involved in HIV‐1 Tat‐induced tight junction protein ZO‐1 translocation and alterations of claudin‐5 expression in brain endothelial cells

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Yu Zhong ◽  
Bernhard Hennig ◽  
Michal Toborek
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Tight Junction Protein ◽  
Brain Endothelial Cells ◽  
Junction Protein ◽  
Hiv 1

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 PPARs attenuate HIV‐1‐induced dysregulation of tight junction protein expression in human brain endothelial cells

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Wen Huang ◽  
Ibolya E András ◽  
Sung Yong Eum ◽  
Yu Zhong ◽  
Pierre‐Olivier Couraud ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Tight Junction ◽  
Human Brain ◽  
Tight Junction Protein ◽  
Brain Endothelial Cells ◽  
Tight Junction Protein Expression ◽  
Junction Protein ◽  
Hiv 1

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 Endothelial-specific insulin receptor substrate-1 overexpression worsens neonatal hypoxic-ischemic brain injury via mTOR-mediated tight junction disassembly

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi-Fang Tu ◽  
Si-Tse Jiang ◽  
Chi-Wu Chiang ◽  
Li-Ching Chen ◽  
Chao-Ching Huang
Keyword(s):  
Endothelial Cells ◽  
Brain Injury ◽  
Tight Junction ◽  
Insulin Receptor ◽  
Vascular Endothelial Cells ◽  
Tight Junction Protein ◽  
Insulin Receptor Substrate ◽  
Vascular Endothelial ◽  
Transgenic Rats ◽  
Junction Protein

AbstractHypoxic-ischemic (HI) encephalopathy is the major cause of mortality and disability in newborns. The neurovascular unit is a major target of acute and chronic brain injury, and therapies that protect simultaneously both neurons and vascular endothelial cells from neonatal HI injury are in demand. Insulin receptors and its key downstream molecule-insulin receptor substrate −1 (IRS-1) are potential neuroprotective targets and expressed both in neuron and endothelial cells. To investigate whether IRS-1 can act similarly in neurons and vascular endothelial cells in protecting neurovascular units and brain form HI injury, we found that neuron-specific IRS-1 transgenic rats showed reduced neurovascular injury and infarct volumes, whereas endothelial-specific IRS-1 transgenic rats showed increased blood-brain barrier (BBB) disruption and exaggerated neurovascular injury after neonatal HI brain injury. Endothelial-specific IRS-1 overexpression increased vascular permeability and disassembled the tight junction protein (zonula occludens-1) complex. Inhibition of mammalian target of rapamycin (mTOR) by rapamycin preserved tight junction proteins and attenuated BBB leakage and neuronal apoptosis after HI in the endothelial-specific IRS-1 transgenic pups. Together, our findings suggested that neuronal and endothelial IRS-1 had opposite effects on the neurovascular integrity and damage after neonatal HI brain injury and that endothelial IRS-1 worsens neurovascular integrity after HI via mTOR-mediated tight junction protein disassembly.

scholarly journals Effects of fasudil on blood-brain barrier integrity

2021 ◽  
Author(s):  
Kei Sato ◽  
Shinsuke Nakagawa ◽  
Yoichi Morofuji ◽  
Yuki Matsunaga ◽  
Takashi Fujimoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Tight Junction ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Tight Junction Protein ◽  
Brain Barrier ◽  
Blood Brain ◽  
Junction Protein ◽  
Culture Models

Abstract Background Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model. Medhods: BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6-hour OGD/24-hour reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using immunohistochemistry and western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells. Results We found that treatment with 0.3–30 µM of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes. Conclusions Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.

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