scholarly journals Inhibitory Effect of Essential Oil from Fructus Alpiniae zerumbet on Endothelial-to-Mesenchymal Transformation Induced by TGF-β1 and down-regulating KLF4

2020 ◽  
Author(s):  
shuang zhao ◽  
Li He ◽  
Mei Huang ◽  
Meng xin Tu ◽  
Xiang chun Shen ◽  
...  
Keyword(s):  
Protective Effect ◽  
Protein Interactions ◽  
Umbilical Vein ◽  
Histone H3 ◽  
Inhibitory Effect ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Migration Ability ◽  
Umbilical Vein Endothelial Cells ◽  
Mesenchymal Transformation

Abstract Background: Endothelial Mesenchymal Transformation (EndMT) contributes to the development of cardiovascular disease. Krüpple factor 4 (KLF4) is a zinc finger transcription factor whose N-terminus can recruit acetyltransferase to promote histone acetylation, thereby affecting the transcription activation of downstream genes. Our previous studies have shown that EOFAZ has protective effects on HUVECs oxidative stress induced by TGF-β1. However, whether EOFAZ has a protective effect on EndMT induced by TGF-β1 and whether it is related to the regulation of downstream signals by KLF4 has not yet been elucidated.Methods: The protective effects of EOFAZ were evaluated in TGF-β1-treated EndMT in Human umbilical vein endothelial cells (HUVECs). Cell mobility was evaluated by wound-healing, transwell assays and angiogenesis experiment. Western blot analysis, Quantitative real-time PCR analysis (qRT-PCR) and immunofluorescence staining were utilized to determine the expression of endothelial and mesenchymal markers , KLF4, Histone 3 acetylation and Notch/Snail signaling axis. Small interfering RNA (siRNA) and adenovirus infection were used to determine the effciency of KLF4 inhibition and overexpression. Immunoprecipitation experiments were performed to analyze protein interactions.Results: We reported that EOFAZ has a protective effect on EndMT induced by TGF-β1. Deletion of KLF4 inhibited EndMT induced by TGF-β1 in HUVECs. EOFAZ pretreatment and KLF4 knockout reduced the migration ability of HUVECs , and increased endothelial markers accompanied by decreased mesenchymal markers, meanwhile caused the change of Notch/Snail signal axis. In addition, TGF-β1 upregulated the expression of KLF4, while the high expression of KLF4 promoted the acetylation of histone H3, and there was a protein interaction between the acetylated histone H3 and KLF4. Conclusions: These results suggest that TGF-β1 may promote the acetylation of histone H3 and activate the transduction of Notch/Snail signal axis by up-regulating the expression of KLF4, which may induce EndMT and this effect may be reversed by EOFAZ. Therefore, EOFAZ may inhibit EndMT induced by TGF-β1 by down-regulating KLF4 expression.

scholarly journals The protective effect of thymoquinone on tert-butylhydroquinone induced cytotoxicity in human umbilical vein endothelial cells

2019 ◽  
Vol 8 (6) ◽  
pp. 1050-1056
Author(s):  
Zahra Karimi ◽  
Maryam Ghaffari ◽  
Jafar Ezzati Nazhad Dolatabadi ◽  
Parvin Dehghan
Keyword(s):  
Endothelial Cells ◽  
Protective Effect ◽  
Food Industry ◽  
Umbilical Vein ◽  
Protective Agent ◽  
Protective Effects ◽  
Oxidative Rancidity ◽  
Dapi Staining ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Abstract 2-tert-Butyl-4-hydroquinone (TBHQ) is used for inhibition of oxidative rancidity in the food industry. However, this antioxidant can stimulate cytotoxicity in human umbilical vein endothelial cells (HUVECs). Thus, potential protective effects of thymoquinone (TQ) against TBHQ-induced cytotoxicity were investigated. Cytotoxicity was evaluated via MTT, flow cytometry, DAPI staining and DNA fragmentation methods. The obtained results revealed that treatment of HUVECs with TQ enhanced the cell viability rate and it had potential to reduce the cytotoxicity effect of TBHQ in cells. Also, in a combined regime of TQ and TBHQ, apoptosis was reduced compared to the cells treated with TBHQ (p < 0.05). Similarly, TQ had a protective effect on DNA and chromatin fragmentation of the cells treated with TBHQ. Finally, it can be concluded that TQ could be used as a protective agent against cytotoxicity induced by TBHQ in HUVECs.

Grx1 Antagonized High Glucose-Induced Apoptosis in Endothelial Cells through Inhibition of Jnk Pathway

2011 ◽  
Vol 345 ◽  
pp. 257-262
Author(s):  
Hai Tao Yu ◽  
Li Ling Yue ◽  
Chun Jing Zhang
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Umbilical Vein ◽  
Annexin V ◽  
Inhibitory Effect ◽  
Expression Level ◽  
Protective Effects ◽  
Jnk Pathway ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

To investigate the mechanism underlying the protective effects of glutaredoxin-1 (Grx1) against high glucose-induced apoptosis in umbilical vein endothelial cells. The proliferation of cells was measured by MTT assay. The cells ultra-structure were observed by TEM and the apoptotic rate was detected by the immunofluorescent of Annexin V－FITC/PI with flow cytometer. The level of p-JNK and JNK were evaluated by western bloting. Results showed that Grx1 prevented the inhibitory effect on cell viability induced by high glucose; Grxl could inhibit high glucose-induced apoptosis and restrain apoptosis rate of endothelial cell significantly. The expression level of p-JNK protein significantly increased while that of JNK protein has no insignificantly chang in cells of the high glucose group, After pretreatment with Grx1, the expression level of p-JNK protein decreased. These results demonstrated that Grx1 has protective effects against high glucose-induced apoptosis in HUVECs through inhibition of JNK pathway.

scholarly journals Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1β-activated human endothelial cells

2005 ◽  
Vol 289 (4) ◽  
pp. H1669-H1675 ◽  
Author(s):  
John P. Cullen ◽  
Shariq Sayeed ◽  
Ying Jin ◽  
Nicholas G. Theodorakis ◽  
James V. Sitzmann ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Binding Activity ◽  
Protective Effects ◽  
Monocyte Adhesion ◽  
Monocyte Chemotactic Protein ◽  
Chemotactic Protein ◽  
Subendothelial Space ◽  
Umbilical Vein Endothelial Cells

The aim of this study was to determine the effect of ethanol (EtOH) on endothelial monocyte chemotactic protein-1 (MCP-1) expression. IL-1β increased the production of MCP-1 by human umbilical vein endothelial cells from undetectable levels to ∼900 pg/ml at 24 h. EtOH dose-dependently inhibited IL-1β-stimulated MCP-1 secretion as determined by ELISA: 25 ± 1%, 35 ± 7%, and 65 ± 5% inhibition for 1, 10, and 100 mM EtOH, respectively, concomitant with inhibition of monocyte adhesion to activated endothelial cells. Similarly, EtOH dose-dependently inhibited IL-1β-stimulated MCP-1 mRNA expression. Experiments with actinomycin D demonstrated that EtOH decreased the stability of MCP-1 mRNA. In addition, EtOH significantly reduced NF-κB and AP-1 binding activity induced by IL-1β and inhibited MCP-1 gene transcription. Binding of 125I-labeled MCP-1 to its receptor (CCR2) on THP-1 human monocytic cells was not affected by EtOH treatment. Modulation of the expression of MCP-1 represents a mechanism whereby EtOH could inhibit atherogenesis by blocking the crucial early step of monocyte adhesion and subsequent recruitment to the subendothelial space. These actions of EtOH may underlie, in part, its cardiovascular protective effects in vivo.

scholarly journals Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2736-2744 ◽  
Author(s):  
John H. Cleator ◽  
Wen Qin Zhu ◽  
Douglas E. Vaughan ◽  
Heidi E. Hamm
Keyword(s):  
Von Willebrand Factor ◽  
Umbilical Vein ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Differential Regulation ◽  
Cell Surface Expression ◽  
Protease Activated Receptors ◽  
Umbilical Vein Endothelial Cells ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThrombin-mediated endothelial-cell release of von Willebrand factor (VWF) and P-selectin functionally links protease-activated receptors (PARs) to thrombosis and inflammation. VWF release can be stimulated by both Ca2+ and cAMP, and, although both VWF and P-selectin are found in Weibel-Palade bodies (WPBs), we found that their release could be differentially regulated. In these studies, human umbilical vein endothelial cells stimulated with cAMP or PAR2-AP led to a delayed release of VWF and significantly less P-selectin release compared with histamine, thrombin, or PAR1-AP. Dose-response studies revealed that PAR2-AP was significantly less efficacious in promoting the release of P-selectin compared with VWF. PAR2-AP–induced robust stimulation of intracellular Ca2+ coupled with a significantly greater inhibitory effect of calcium chelation on release of VWF compared with cell-surface expression of P-selectin, suggests an additional Ca2+-independent pathway involved in release of P-selectin. PAR2-AP failed to increase global cAMP levels; however, inhibition of protein kinase A led to a significant attenuation of PAR2-AP–mediated release of VWF. Confocal microscopy studies revealed that PAR2 and forskolin caused preferential release of a population of Weibel-Palade bodies (WPBs) consisting of only VWF. Thus, WPBs are pharmacologically and morphologically heterogeneous, and distinct granule populations are susceptible to differential regulation.

Hypoxia-induced pulmonary endothelin-1 expression is unaltered by nitric oxide

2002 ◽  
Vol 92 (3) ◽  
pp. 1152-1158 ◽  
Author(s):  
Scott Earley ◽  
Leif D. Nelin ◽  
Louis G. Chicoine ◽  
Benjimen R. Walker
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Promoter Activity ◽  
Umbilical Vein ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Exposure ◽  
Mrna Levels ◽  
Protective Effects ◽  
No Donor ◽  
Umbilical Vein Endothelial Cells

Nitric oxide (NO) attenuates hypoxia-induced endothelin (ET)-1 expression in cultured umbilical vein endothelial cells. We hypothesized that NO similarly attenuates hypoxia-induced increases in ET-1 expression in the lungs of intact animals and reasoned that potentially reduced ET-1 levels may contribute to the protective effects of NO against the development of pulmonary hypertension during chronic hypoxia. As expected, hypoxic exposure (24 h, 10% O2) increased rat lung ET-1 peptide and prepro-ET-1 mRNA levels. Contrary to our hypothesis, inhaled NO (iNO) did not attenuate hypoxia-induced increases in pulmonary ET-1 peptide or prepro-ET-1 mRNA levels. Because of this surprising finding, we also examined the effects of NO on hypoxia-induced increases in ET peptide levels in cultured cell experiments. Consistent with the results of iNO experiments, administration of the NO donor S-nitroso- N-acetyl-penicillamine to cultured bovine pulmonary endothelial cells did not attenuate increases in ET peptide levels resulting from hypoxic (24 h, 3% O2) exposure. In additional experiments, we examined the effects of NO on the activity of a cloned ET-1 promoter fragment containing a functional hypoxia inducible factor-1 binding site in reporter gene experiments. Whereas moderate hypoxia (24 h, 3% O2) had no effect on ET-1 promoter activity, activity was increased by severe hypoxic (24 h, 0.5% O2) exposure. ET-1 promoter activity after S-nitroso- N-acetyl-penicillamine administration during severe hypoxia was greater than that in normoxic controls, although activity was reduced compared with that in hypoxic controls. These findings suggest that hypoxia-induced pulmonary ET-1 expression is unaffected by NO.

Some Indian herbs have protective effects against deleterious effects of ochratoxin A in broiler chicks

2021 ◽  
pp. 1-14
Author(s):  
S.D. Stoev ◽  
K. Dimitrov ◽  
I. Zarkov ◽  
T. Mircheva ◽  
D. Zapryanova ◽  
...  
Keyword(s):  
Body Weight ◽  
Protective Effect ◽  
Ochratoxin A ◽  
Relative Weight ◽  
Fine Powder ◽  
Inhibitory Effect ◽  
Feed Additives ◽  
Tinospora Cordifolia ◽  
Broiler Chicks ◽  
Protective Effects

A protective effect of two herbs, Glycyrrhiza glabra and Tinospora cordifolia, given as feed additives was observed against the growth inhibitory effect of ochratoxin A (OTA) and associated immunosuppression and biochemical or pathomorphological changes. The feed levels of 3 mg/kg OTA and fine powder of one of both herbs were given during a period of 32 days to female broiler chicks divided into 3 experimental and 1 control groups (14 chicks per group). The observed pathological and biochemical changes, the changes in relative organs’ weight and body weight, and the decrease of antibody titer against Newcastle disease were more pronounced in the OTA-treated chicks without herbal supplementation, and less pronounced in the chicks treated additionally with G. glabra or T. cordifolia as was shown by the better feed performance and the higher body weight in the chicks treated with the herbs. The higher relative weight of lymphoid organs of the chicks supplemented with both herbs revealed their beneficial effects on the immune system. The hepatoprotective effect of both herbs was evident, being stronger in the chicks additionally supplemented with G. glabra shown by the pathomorphological findings and by the lower levels of aspartate transaminase (131.1 U/l) compared to chicks given only OTA (156.0 U/l). A protective effect of T. cordifolia on the bone marrow and kidneys was found as was shown by the lower levels of uric acid (382.9 μmol/l) compared to chicks given only OTA (466.9 μmol/l).

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