P120-Catenin Inhibits Endotoxin-Induced Apoptosis In Pulmonary Endothelial Cells

2012 ◽  
Author(s):  
Guochang Hu ◽  
Yan-lei Wang ◽  
Richard Minshall ◽  
Zhibo Yan ◽  
Asrar Malik
Keyword(s):  
Endothelial Cells ◽  
P120 Catenin ◽  
Pulmonary Endothelial Cells ◽  
Induced Apoptosis

scholarly journals p53 Mediates Cigarette Smoke–Induced Apoptosis of Pulmonary Endothelial Cells

2011 ◽  
Vol 44 (3) ◽  
pp. 323-332 ◽  
Author(s):  
Rachel Damico ◽  
Tiffany Simms ◽  
Bo S. Kim ◽  
Zenar Tekeste ◽  
Henry Amankwan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cigarette Smoke ◽  
Pulmonary Endothelial Cells ◽  
Induced Apoptosis

scholarly journals LPS-induced decrease in intracellular labile zinc, [Zn]i, contributes to apoptosis in cultured sheep pulmonary artery endothelial cells

2011 ◽  
Vol 300 (4) ◽  
pp. L624-L632 ◽  
Author(s):  
Kalidasan Thambiayya ◽  
Karla J. Wasserloos ◽  
Zhentai Huang ◽  
Valerian E. Kagan ◽  
Claudette M. St. Croix ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Annexin V ◽  
Epifluorescence Microscopy ◽  
Cytochrome C Release ◽  
Pulmonary Endothelium ◽  
Pulmonary Endothelial Cells ◽  
Zinc Chelator ◽  
Labile Pool ◽  
Induced Apoptosis

A role in signal transduction for a vanishingly small labile pool of intracellular zinc ([Zn]i) has been inferred by the sensitivity of various physiological pathways to zinc chelators such as N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and/or associations with changes in nonprotein-bound zinc-sensitive fluorophores. Although we ( 44 ) reported that LPS-induced apoptosis in cultured sheep pulmonary artery endothelial cells (SPAEC) was exacerbated by TPEN, 1) we did not detect acute (30 min) changes in [Zn]i, and 2) it is unclear from other reports whether LPS increases or decreases [Zn]i and whether elevations or decreases in [Zn]i are associated with cell death and/or apoptosis. In the present study, we used both chemical (FluoZin-3 via live cell epifluorescence microscopy and fluorescence-activated cell sorting) and genetic (luciferase activity of a chimeric reporter encoding zinc-sensitive metal-response element and changes in steady-state mRNA of zinc importer, SLC39A14 or ZIP14) techniques to show that LPS caused a delayed time-dependent (2–4 h) decrease in [Zn]i in SPAEC. A contributory role of decreases in [Zn]i in LPS-induced apoptosis (as determined by caspase-3/7 activation, annexin-V binding, and cytochrome c release) in SPAECs was revealed by mimicking the effect of LPS with the zinc chelator, TPEN, and inhibiting LPS- (or TPEN)-induced apoptosis with exogenous zinc. Collectively, these are the first data demonstrating a signaling role for decrease in [Zn]i in pulmonary endothelial cells and suggest that endogenous levels of labile zinc may affect sensitivity of pulmonary endothelium to the important and complex proapoptotic stimulus of LPS.

scholarly journals Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing SMAD2 Phosphorylation

2015 ◽  
Vol 35 (6) ◽  
pp. 2203-2212 ◽  
Author(s):  
Yong Ji ◽  
Fengying Gao ◽  
Bo Sun ◽  
Jing Hao ◽  
Zhenwei Liu
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Cell Apoptosis ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Pulmonary Endothelial Cells ◽  
Smad2 Phosphorylation ◽  
Induced Apoptosis

Background/Aims: Angiotensin converting enzyme 2 (ACE2) has an established role in suppressing the severity of acute lung injury (ALI), especially when it was applied together with transplantation of human umbilical cord mesenchymal stem cells (uMSCs). Although the effects of ACE2 in ALI are believed to mainly result from its role in hydrolyzing angiotensin II (AngII), which subsequently reduces the vascular tension and subsequent pulmonary accumulation of inflammatory cells, we and others have recently reported a possible role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells. However, the underlying mechanisms remain undetermined. Methods: Here, we analyzed the alteration in lung injury severity in ALI after ACE2, by histology and inflammatory cytokine levels. We analyzed apoptosis-associated proteins in lung after ALI, as well as in cultured endothelial cells treated with nitric oxide (NO). We overexpressed SMAD7 to inhibit SMAD2 signaling in cultured endothelial cells and examined its effects on NO-induced cell apoptosis. Results: ACE2 alleviated severity of lung injury after ALI. ACE2 significantly decreased the ALI-induced apoptosis of pulmonary cells in vivo, and ACE2 protected endothelial cells against NO-induced apoptosis in vitro. NO induced phosphorylation of a key factor of transforming growth factor β (TGF β) receptor signaling, SMAD2, which could be dose-dependently inhibited by ACE2. Inhibition of SMAD2 phosphorylation through expression of its inhibitor SMAD7 significantly inhibited NO-induced cell apoptosis, without need for ACE2. Conclusion: Our data suggest that ACE2-mediated AngII degradation may inhibit AngII-mediated SMAD2-phophorylation, possibly through a TGFβ-independent manner, which subsequently suppresses the ALI-induced cell death. Our results thus reveal a novel molecular pathway that controls the pathogenesis of ALI.

scholarly journals Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262

2015 ◽  
Vol 37 (2) ◽  
pp. 759-767 ◽  
Author(s):  
Hong Bao ◽  
Fengying Gao ◽  
Guogang Xie ◽  
Zhenwei Liu
Keyword(s):  
Endothelial Cells ◽  
Protein Translation ◽  
Mouse Lung ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Pulmonary Endothelial Cells ◽  
Pulmonary Cells ◽  
Induced Apoptosis

Background/Aims: Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI). The effects of ACE2 in ALI have been shown to not only result from its antagonizing hydrolyzing angiotensin II (AngII), which is responsible for reduction in the vascular tension and pulmonary accumulation of inflammatory cells, but also result from a role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells (PECs). Nevertheless, the underlying mechanisms of the role of ACE2 on PEC apoptosis are not completely understood. Methods: Here, we used a bleomycin-induced mouse model for ALI that has been published in our previous studies. We analyzed the mRNA and protein levels of an anti-apoptotic protein Bcl-2 in the ALI-mice that have been treated w/o ACE2. We analyzed miR-4262 levels in the mouse lung in these mice. Bcl-2-targeting miRNAs were predicted using bioinformatics algorithms and a luciferase reporter assay was applied to examine the effects of miR-4262 on the Bcl-2 protein translation upon their binding to 3'-UTR of Bcl-2 mRNA. Adeno-associated viruses carrying either miR-4262 mimics or antisense were injected into ALI-mice without ACE2, and their effects on the apoptosis in mouse lung cells were analyzed by Western blot. Results: ACE2 inhibited the ALI-induced apoptosis of pulmonary cells in vivo partially through upregulation of Bcl-2 protein, but not Bcl-2 mRNA. ACE2 appeared to significantly suppress the upregulation of miR-4262 in mouse lung after ALI. MiR-4262 was found to target 3'-UTR of Bcl-2 mRNA to inhibit its protein translation in PECs. In vivo administration of antisense of miR-4262 decreased apoptosis of pulmonary cells and severity of the ALI in mice. Conclusion: ACE2-induced suppression of miR-4262 partially contribute to the inhibition of the PEC apoptosis after ALI through Bcl-2. MiR-4262 may be a novel promising treatment target for ALI and ARDS.

FAK blunts adenosine-homocysteine-induced endothelial cell apoptosis: requirement for PI 3-kinase

2002 ◽  
Vol 282 (5) ◽  
pp. L1135-L1142 ◽  
Author(s):  
Robert E. Bellas ◽  
Elizabeth O. Harrington ◽  
Kerri Lynn Sheahan ◽  
Julie Newton ◽  
Caroline Marcus ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Focal Adhesion ◽  
Catalytic Domain ◽  
Kinase Inhibitor ◽  
Endothelial Cell Apoptosis ◽  
Phosphatidylinositol 3 Kinase ◽  
Pulmonary Endothelial Cells ◽  
Induced Apoptosis ◽  
Dependent Pathway ◽  
Autophosphorylation Site

Treatment of cultured bovine pulmonary endothelial cells (BPAEC) with adenosine (Ado) alone or in combination with homocysteine (Hc) leads to disruption of focal adhesion complexes, caspase-dependent degradation of components of focal adhesion complexes, and subsequent apoptosis. Endothelial cells transiently overexpressing paxillin or p130Cas cDNAs underwent Ado-Hc-induced apoptosis to an extent similar to that of cells transfected with vector alone. However, overexpression of focal adhesion kinase (FAK) cDNA blunted Ado-Hc-induced apoptosis. FAK constructs lacking the central catalytic domain or containing a point mutation, rendering the catalytic domain enzymatically inactive, did not provide protection from apoptosis. Constructs containing a mutation in the major autophosphorylation site (tyrosine-397) similarly did not prevent cell death. A FAK mutant in amino acid 395, deficient in phosphatidylinositol 3-kinase (PI 3-kinase) binding, was not able to blunt apoptosis. Finally, overexpression of FAK did not provide protection from apoptosis in the presence of LY-294002, a PI 3-kinase inhibitor. Taken together, these data suggest that the survival signals mediated by overexpression of FAK in response to Ado-Hc-induced apoptosis require a PI 3-kinase-dependent pathway.

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