scholarly journals Ticagrelor and clopidogrel suppress NF-κB signaling pathway to alleviate LPS-induced dysfunction in vein endothelial cells

2019 ◽  
Author(s):  
Zhuyin Jia ◽  
Yiwei Huang ◽  
Xiaojun Ji ◽  
Jiaju Sun ◽  
Guosheng Fu
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Coronary Syndrome

Abstract Background: Ticagrelor and clopidogrel, P2Y12 receptor antagonists, can prevent thrombotic events and are used to treat cardiovascular diseases such as acute coronary syndrome and chronic obstructive pulmonary disease, in which inflammation is involved. Moreover, NF-kB is the central regulator of inflammation. Thus, we suspected that ticagrelor and clopidogrel are involved in the regulation of the NF-kB signaling pathway.Methods: After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level and subcellular localization of molecules in the NF-kB signaling pathway, cell viability, apoptosis and the cell cycle, cell migration, and vascular formation were detected using quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence assay, CCK8, flow cytometry, transwell assay, and matrigel, respectively. All data was expressed as the mean ± S.D. The statistical significance of data was assessed by an unpaired two-tailed t-test.Results: Ticagrelor and clopidogrel can inhibit the degradation of IKBa and phosphorylation of p65, prevent p65 from entering the nucleus, reduce the production of TNFa, IL-1, IL-8, IL-6 and IL-2, and alleviate the decrease in cell viability, cell migration and angiogenesis, the changes of cell cycle and apoptosis induced by LPS. Conclusions: Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-kB signaling pathway.

scholarly journals Ticagrelor and clopidogrel suppress NF-κB signaling pathway to alleviate LPS-induced dysfunction in vein endothelial cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhuyin Jia ◽  
Yiwei Huang ◽  
Xiaojun Ji ◽  
Jiaju Sun ◽  
Guosheng Fu
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Coronary Syndrome

Abstract Background Ticagrelor and clopidogrel, P2Y12 receptor antagonists, can prevent thrombotic events and are used to treat cardiovascular diseases such as acute coronary syndrome and chronic obstructive pulmonary disease, in which inflammation is involved. Moreover, NF-B is the central regulator of inflammation. Thus, we suspected that ticagrelor and clopidogrel are involved in the regulation of the NF-ΚB signaling pathway. Methods After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level and subcellular localization of molecules in the NF-ΚB signaling pathway, cell viability, apoptosis and the cell cycle, cell migration, and vascular formation were detected using quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence assay, CCK-8, flow cytometry, transwell assay, and matrigel, respectively. All data was expressed as the mean ± S.D. The statistical significance of data was assessed by an unpaired two-tailed t-test. Results Ticagrelor and clopidogrel can inhibit the degradation of IKBα and phosphorylation of p65, prevent p65 from entering the nucleus, reduce the production of TNFα, IL-1, IL-8, IL-6 and IL-2, and alleviate the decrease in cell viability, cell migration and angiogenesis, the changes of cell cycle and apoptosis induced by LPS. Conclusions Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-ΚB signaling pathway.

scholarly journals Ticagrelor and clopidogrel suppress NF-kB signaling pathway to alleviate LPS-induced dysfunction in vein endothelial cells

2019 ◽  
Author(s):  
Zhuyin Jia ◽  
Yiwei Huang ◽  
Xiaojun Ji ◽  
Jiaju Sun ◽  
Guosheng Fu
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Coronary Syndrome

Abstract Background: Ticagrelor and clopidogrel, P2Y12 receptor antagonists, can prevent thrombotic events and are used to treat cardiovascular diseases such as acute coronary syndrome and chronic obstructive pulmonary disease, in which inflammation is involved. Moreover, NF-kB is the central regulator of inflammation. Thus, we suspected that ticagrelor and clopidogrel are involved in the regulation of the NF-kB signaling pathway.Methods: After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level and subcellular localization of molecules in the NF-kB signaling pathway, cell viability, apoptosis and the cell cycle, cell migration, and vascular formation were detected using quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence assay, CCK-8, flow cytometry, transwell assay, and matrigel, respectively. All data was expressed as the mean ± S.D. The statistical significance of data was assessed by an unpaired two-tailed t-test.Results: Ticagrelor and clopidogrel can inhibit the degradation of IKBa and phosphorylation of p65, prevent p65 from entering the nucleus, reduce the production of TNFa, IL-1, IL-8, IL-6 and IL-2, and alleviate the decrease in cell viability, cell migration and angiogenesis, the changes of cell cycle and apoptosis induced by LPS.Conclusions: Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-kB signaling pathway.

scholarly journals Ticagrelor and clopidogrel suppress NF-κB to treat acute coronary syndrome

2019 ◽  
Author(s):  
Zhuyin Jia ◽  
Yiwei Huang ◽  
Xiaojun Ji ◽  
Jiaju Sun ◽  
Guosheng Fu
Keyword(s):  
Cell Cycle ◽  
Acute Coronary Syndrome ◽  
Cell Migration ◽  
Cell Viability ◽  
Umbilical Vein ◽  
Quantitative Polymerase Chain Reaction ◽  
Statistical Significance ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
Coronary Syndrome

Abstract Background: Inflammatory cytokines are involved in acute coronary syndrome (ACS),and NF-kB is the central regulator of inflammation. Moreover, ticagrelor and clopidogrelcan prevent thrombotic events and improve the care of patients with ACS. Thus, we speculated that ticagrelor and clopidogrel relieve ACS by regulating NF-kB pathway. Methods: After human umbilical vein endothelial cells (HUVECs) were cultured with ticagrelor or clopidogrel and given lipopolysaccharide (LPS) and CD14, the mRNA levels of related inflammatory factors, the protein level changes of molecules in the NF-kB pathway, and the changes in cell viability, apoptosis and the cell cycle, cell migration, vascular formation and other vital activities were detected using quantitative Polymerase chain reaction (qPCR), Western blotting and immunofluorescence assay, CCK8， flow cytometry, transwell assay, matrigel, respectively. All data was expressed as the mean ± S.D. The statistical significance of data was assessedby an unpaired two-tailed t-test. Results: Ticagrelor and clopidogrel can suppress the NF-kB pathway by inhibiting the phosphorylation and entry into the nucleus of p65, restraining the degradation of IKBa, improving cell viability, restoring the cell cycle, cell migration and angiogenic ability, and inhibiting apoptosis. Conclusions: Ticagrelor and clopidogrel alleviate cellular dysfunction through suppressing NF-kB signaling to treat acute coronary syndrome.

scholarly journals HIV-1 Transactivator Protein Induces ZO-1 and Neprilysin Dysfunction in Brain Endothelial Cells via the Ras Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Wenlin Jiang ◽  
Wen Huang ◽  
Yanlan Chen ◽  
Min Zou ◽  
Dingyue Peng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Ras Signaling ◽  
Mrna Levels ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Ras Signaling Pathway ◽  
Transactivator Protein ◽  
Hiv 1

Amyloid beta (Aβ) deposition is increased in human immunodeficiency virus-1- (HIV-1-) infected brain, but the mechanisms are not fully understood. The aim of the present study was to evaluate the role of Ras signaling in HIV-1 transactivator protein- (Tat-) induced Aβ accumulation in human cerebral microvascular endothelial cells (HBEC-5i). Cell viability assay showed that 1 μg/mL Tat and 20 μmol/L of the Ras inhibitor farnesylthiosalicylic acid (FTS) had no significant effect on HBEC-5i cell viability after 24 h exposure. Exposure to Tat decreased protein and mRNA levels of zonula occludens- (ZO-) 1 and Aβ-degrading enzyme neprilysin (NEP) in HBEC-5i cells as determined by western blotting and quantitative real-time polymerase chain reaction. Exposure to Tat also increased transendothelial transfer of Aβ and intracellular reactive oxygen species (ROS) levels; however, these effects were attenuated by FTS. Collectively, these results suggest that the Ras signaling pathway is involved in HIV-1 Tat-induced changes in ZO-1 and NEP, as well as Aβ deposition in HBEC-5i cells. FTS partially protects blood-brain barrier (BBB) integrity and inhibits Aβ accumulation.

scholarly journals Fisetin Suppresses the Proliferation and Metastasis of Renal Cell Carcinoma through Upregulation of MEK/ERK-Targeting CTSS and ADAM9

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 948 ◽  
Author(s):  
Hsieh ◽  
Tsai ◽  
Yang ◽  
Chiou ◽  
Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Migration ◽  
Cell Viability ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Mapk Signaling ◽  
Migration And Invasion ◽  
Proliferation And Metastasis

Fisetin, a natural flavonoid, is known to have anticarcinogenic effects against several cancers, but its role in mediating renal cell carcinoma (RCC) progression has not been delineated. Cell viability, cytotoxicity, and cell cycle distribution were measured using the 3‐(4,5‐cimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay and propidium iodide staining with flow cytometry. The in vitro migration and invasion assay was used to examine in vivo cell migration and invasion. Human protease antibody array analysis was conducted with cell migration/invasion-related proteins. Western blotting and quantitative reverse transcription polymerase chain reaction were used for assessing protein expression related to the cell cycle, cell invasion, and mitogen-activated protein kinase (MAPK) signaling pathway. We found that fisetin significantly inhibited cell viability through cell cycle arrest in the G2/M phase, in addition to downregulating cyclin D1 and upregulating p21/p27. Fisetin inhibited the migration and invasion of human RCC cells through the downregulation of CTSS and a disintegrin and metalloproteinase 9 (ADAM9). Fisetin also upregulated ERK phosphorylation in 786-O and Caki-1 cells. Furthermore, treatment with a MEK inhibitor (UO126) reduced the inhibitory effects of fisetin on the metastasis of RCC cells through the ERK/CTSS/ADAM9 pathway. Fisetin inhibits proliferation and metastasis of RCC cells by downregulating CTSS and ADAM9 through the MEK/ERK signaling pathway. These findings indicate that fisetin is a promising antitumor agent against RCC.

scholarly journals Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 465
Author(s):  
Omer Anis ◽  
Ajjampura C. Vinayaka ◽  
Nurit Shalev ◽  
Dvora Namdar ◽  
Stalin Nadarajan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Migration ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
High Performance ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Quantitative Polymerase Chain Reaction ◽  
Migration And Invasion ◽  
Xtt Assay

Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.

scholarly journals CircSOD2 induced epigenetic alteration drives hepatocellular carcinoma progression through activating JAK2/STAT3 signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Zhongwei Zhao ◽  
Jingjing Song ◽  
Bufu Tang ◽  
Shiji Fang ◽  
Dengke Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Migration ◽  
Real Time ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Signaling Axis

Abstract Background Emerging evidence suggests that circular RNAs play critical roles in disease development especially in cancers. Previous genome-wide RNA-seq studies found that a circular RNA derived from SOD2 gene was highly upregulated in hepatocellular carcinoma (HCC), however, the role of circSOD2 in HCC remains largely unknown. Methods The expression profiling of circSOD2 and microRNA in HCC patients were assessed by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). SiRNA or CRISPR-CAS9 were used to silence gene expression. The biological function of circSOD2 in HCC was investigated using in vitro and in vivo studies including, trans-well cell migration, cell apoptosis, cell cycle, CCK8, siRNA interference, western blots, and xenograft mouse model. The underlying molecular mechanism was determined by Chromatin Immunoprecipitation quantitative real time PCR (ChIP-qPCR), bioinformatic analysis, biotin-pull down, RNA immunoprecipitation, 5-mc DNA pulldown and luciferase assays. Results In accordance with previous sequencing results, here, we demonstrated that circSOD2 was highly expressed in HCC tumor tissues compared with normal liver tissues. Mechanically, we showed that histone writer EP300 and WDR5 bind to circSOD2 promoter and trigger its promoter H3K27ac and H3K4me3 modification, respectively, which further activates circSOD2 expression. SiRNA mediated circSOD2 suppression impaired liver cancer cell growth, cell migration, prohibited cell cycle progression and in vivo tumor growth. By acting as a sponge, circSOD2 inhibits miR-502-5p expression and rescues miR-502-5p target gene DNMT3a expression. As a DNA methyltransferase, upregulated DNMA3a suppresses SOCS3 expression by increasing SOCS3 promoter DNA methylation. This event further accelerates SOCS3 downstream JAK2/STAT3 signaling pathway activation. In addition, we also found that activated STAT3 regulates circSOD2 expression in a feedback way. Conclusion The novel signaling axis circSOD2/miR-502-5p/DNMT3a/JAK2/STAT3/circSOD2 provides a better understanding of HCC tumorigenesis. The molecular mechanism underlying this signaling axis offers new prevention and treatment of HCC.

scholarly journals CRIF1 deficiency suppresses endothelial cell migration via upregulation of RhoGDI2

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256646
Author(s):  
Harsha Nagar ◽  
Seonhee Kim ◽  
Ikjun Lee ◽  
Su-Jeong Choi ◽  
Shuyu Piao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Cellular Migration ◽  
Endothelial Cell Migration ◽  
Migration And Invasion ◽  
Mitochondrial Functions

Rho GDP-dissociation inhibitor (RhoGDI), a downregulator of Rho family GTPases, prevents nucleotide exchange and membrane association. It is responsible for the activation of Rho GTPases, which regulate a variety of cellular processes, such as migration. Although RhoGDI2 has been identified as a tumor suppressor gene involved in cellular migration and invasion, little is known about its role in vascular endothelial cell (EC) migration. CR6-interacting factor 1 (CRIF1) is a CR6/GADD45-interacting protein with important mitochondrial functions and regulation of cell growth. We examined the expression of RhoGDI2 in CRIF1-deficient human umbilical vein endothelial cells (HUVECs) and its role in cell migration. Expression of RhoGDI2 was found to be considerably higher in CRIF1-deficient HUVECs along with suppression of cell migration. Moreover, the phosphorylation levels of Akt and CREB were decreased in CRIF1-silenced cells. The Akt-CREB signaling pathway was implicated in the changes in endothelial cell migration caused by CRIF1 downregulation. In addition to RhoGDI2, we identified another factor that promotes migration and invasion of ECs. Adrenomedullin2 (ADM2) is an autocrine/paracrine factor that regulates vascular tone and other vascular functions. Endogenous ADM2 levels were elevated in CRIF1-silenced HUVECs with no effect on cell migration. However, siRNA-mediated depletion of RhoGDI2 or exogenous ADM2 administration significantly restored cell migration via the Akt-CREB signaling pathway. In conclusion, RhoGDI2 and ADM2 play important roles in the migration of CRIF1-deficient endothelial cells.

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