Effects and mechanism of arachidonic acid against TNF-α induced apoptosis of endothelial cells

2020 ◽  
pp. 1-7
Author(s):  
Ji-Xiong Chen ◽  
Xiao-Yan Huang ◽  
Ping Wang ◽  
Wen-Ting Lin ◽  
Wen-Xing Xu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Arachidonic Acid Metabolite ◽  
Apoptotic Cells ◽  
Endothelial Cell Apoptosis ◽  
Tnf Α

This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor necrosis factor-alpha (TNF-α). After human umbilical vein endothelial cells were cultured, TNF-α/ActD, 14, 15-EET, and HMR-1098 were added, respectively, into the culture medium. The apoptosis level of endothelial cells was detected by flow cytometry. After TNF-α/ActD induced endothelial cell apoptosis, flow cytometry staining showed that endothelial cell apoptosis increased significantly, and the apoptotic cells were significantly reduced after the addition of 14, 15-EET. However, the apoptotic cells significantly increased after the addition of HMR-1098. Western Blot results showed that the phosphorylation levels of LC3-II and AMPK were increased after TNF-α/ActD induction, and the increase was noticeable after the addition of 14, 15-EET. However, the phosphorylation levels of LC3-II and AMPK significantly decreased after the addition of HMR-1098. The activity of Caspase-8 and -9 decreased significantly after the addition of 14, 15-EET but increased after the addition of HMR-1098. Arachidonic acid can inhibit TNF-α induced endothelial cell apoptosis by upregulating autophagy.

scholarly journals Proteome-Scale Profiling Reveals MAFG and MAFF as Two Novel Candidate Key Transcription Factors Involved in Palmitic acid Induced Umbilical Vein Endothelial Cells Apoptosis

2020 ◽  
Author(s):  
Mangyuan Wang ◽  
Fen Liu ◽  
Binbin Fang ◽  
Qiang Huo ◽  
Yining Yang
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
P Value ◽  
Vascular Endothelial ◽  
Endothelial Cell Apoptosis ◽  
Family Protein ◽  
Umbilical Vein Endothelial Cells

Abstract Backgrounds: Vascular endothelial cell apoptosis is the first risk factor of atherosclerosis (AS), and it can be induced by high doses of glucose and palmitic acid (PA). The purpose of our study is to use a new generation of high-throughput transcription factors (TFs) detecting method to identify novel candidate key TFs involved in PA-induced vascular endothelial cell apoptosis.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with 0µM PA (control group), 250µM PA (group 1), or 500µM PA (group 2). Candidate TFs among the three groups were determined by significant changes according to t-test, and pathway enrichment, western blot (WB) and RT-qPCR were then performed.Results: Fifty-one TFs showing with significant p value were identified, and 24 TFs with significant p value plus fold change > 2 and with dose-dependence were identified with 12 TFs biologically validated in former studies. Two of the remaining 12 novel TFs, v-maf musculoaponeurotic fibrosarcoma oncogene family protein G (MAFG) and v-maf musculoaponeurotic fibrosarcoma oncogene family protein F (MAFF), were matched to AS known signalling pathways and were validated by WB and RT-qPCR in our study.Conclusions: We identified MAFG and MAFF as novel candidate key TFs in vascular endothelial cell apoptosis, which is the key initial process of AS.

Regulation of nicotine-induced apoptosis of pulmonary artery endothelial cells by treatment of N-acetylcysteine and vitamin E

2007 ◽  
Vol 26 (7) ◽  
pp. 595-602 ◽  
Author(s):  
R. Demiralay ◽  
N. Gürsan ◽  
H. Erdem
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vitamin E ◽  
Pulmonary Artery ◽  
Cell Apoptosis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Endothelial Cell Apoptosis ◽  
Antioxidant Agents ◽  
Tnf Α

This study investigated the frequency of apoptosis in rat pulmonary artery endothelial cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO), tumour necrosis factor alpha (TNF-α ), and vascular endothelial growth factor (VEGF) in nicotine-induced vascular damage and the protective effects of two known antioxidant agents, N-acetylcysteine (NAC) and vitamin E. Female Wistar rats were divided into four groups, each composed of nine rats: negative control group, positive control group, NACtreated group (500 mg/kg), and vitamin E-treated group (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Lung tissue samples were stained with hematoxylin-eosin (H&E) for histopathological assessments. Apoptosis level in endothelial cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF-α and VEGF in endothelial cells, and perivascular MPO activity were evaluated by immunohistochemistry. The treatments with NAC and vitamin E significantly reduced the rate of nicotine-induced endothelial cell apoptosis. NAC and vitamin E significantly reduced the increases in the local production of TNF-α and VEGF, and perivascular MPO activity. This findings suggest that NAC can be as effective as vitamin E in protecting against nicotine-induced endothelial cell apoptosis. Human & Experimental Toxicology (2007) 26: 595—602.

Role of protein kinase C β2 activation in TNF-α-induced human vascular endothelial cell apoptosis

2009 ◽  
Vol 87 (3) ◽  
pp. 221-229 ◽  
Author(s):  
Fang Wang ◽  
Hui-min Liu ◽  
Michael G. Irwin ◽  
Zhong-yuan Xia ◽  
Zhiyong Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Apoptosis ◽  
Human Vascular Endothelial Cell ◽  
Kinase C ◽  
Tnf Α

The circulatory inflammatory cytokine tumor necrosis factor alpha (TNF-α) is increased in pathologic conditions that initiate or exacerbate vascular endothelial injury, such as diabetes. Protein kinase C (PKC) has been shown to play a critical role in TNF-α-induced human endothelial cell apoptosis. However, the relative roles played by specific isoforms of PKC in TNF-α-induced human endothelial cell apoptosis have not been addressed. We investigated the effects of a selective PKCβ2 inhibitor (CGP53353) on TNF-α-induced apoptosis in human vascular endothelial cells (cell line ECV304) and on the production of reactive oxygen species and nitric oxide, and compared its effects with rottlerin, a reagent that has been shown to reduce PKCδ protein levels. Cultured human vascular endothelial cells (ECV304) were treated for 24 h with one of 4 regimes: 40 ng/mL TNF-α alone (TNF-α), TNF-α with 10 µmol/L rottlerin (T+rottlerin), TNF-α with 1 µmol/L CGP53353 (T+CGP), or untreated (control). Cell viability was measured by MTT assay, and cell apoptosis was assessed by flow cytometry. TNF-α-induced endothelial cell apoptosis was associated with dramatic increases in production of intracellular hydrogen peroxide (approximately 20 times greater than control) and superoxide (approximately 16 times greater than control), as measured by dichlorofluorescein and dihydroethidium fluorescent staining, respectively. This increase was accompanied by reduced activity of superoxide dismutase and glutathione peroxidase and, subsequently, an increase in the lipid peroxidation product malondialdehyde. CGP53353, but not rottlerin, abolished or attenuated all these changes. We conclude that PKCβ2 plays a major role in TNF-α-induced human vascular endothelial cell apoptosis.

scholarly journals DAXX mediates high phosphate-induced endothelial cell apoptosis in vitro through activating ERK signaling

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9203
Author(s):  
Shu Wang ◽  
Mingyu Wu ◽  
Ling Qin ◽  
Yaxiang Song ◽  
Ai Peng
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Kidney Diseases ◽  
Umbilical Vein ◽  
Additional Treatment ◽  
Erk Signaling ◽  
Death Domain ◽  
Endothelial Cell Apoptosis

Backgroud and Purpose Hyperphosphatemia, which is a high inorganic phosphate (Pi) level in the serum, promotes endothelial cells dysfunction and is associated with cardiovascular diseases in patients with chronic kidney diseases (CKD). However, the underlying mechanism of high Pi-induced endothelia cell apoptosis remains unclear. Methods Human umbilical vein endothelial cells (HUVECs) were treated with normal Pi (1.0 mM) and high Pi (3.0 mM), and then cell apoptosis, abnormal gene expression and potential signaling pathway involvement in simulated hyperphosphatemia were examined using flow cytometry, quantitative PCR (qPCR) and western blot analysis. A two-step 5/6 nephrectomy was carried out to induce CKD and biochemical measurements were taken. Results The rat model of CKD revealed that hyperphosphatemia is correlated with an increased death-domain associated protein (DAXX) expression in endothelial cells. In vitro, high Pi increased the mRNA and protein expression level of DAXX in HUVECs, effects that were reversed by additional phosphonoformic acid treatment. Functionally, high Pi resulted in a significantly increased apoptosis in HUVECs, whereas DAXX knockdown markedly repressed high Pi-induced cell apoptosis, indicating that DAXX mediated high Pi-induced endothelial cell apoptosis. High Pi treatment and DAXX overexpression induced the activation of extracellular regulated protein kinases (ERKs), while DAXX knockdown inhibited high Pi-induced ERKs activation. Finally, we demonstrated that DAXX overexpression induced HUVECs apoptosis in the presence of normal Pi, whereas additional treatment with U0126 (a specific ERK inhibitor) reversed that effect. Conclusion Upregulated DAXX promoted high Pi-induced HUVECs apoptosis by activating ERK signaling and indicated that the DAXX/ERK signaling axis may be served as a potential target for CKD therapy.

CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications

Blood ◽  
2002 ◽  
Vol 99 (8) ◽  
pp. 2940-2947 ◽  
Author(s):  
Anne Janin ◽  
Christophe Deschaumes ◽  
Marjan Daneshpouy ◽  
Jérôme Estaquier ◽  
Juliette Micic-Polianski ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Specific Antibody ◽  
Cell Apoptosis ◽  
Cell Types ◽  
Endothelial Cell Apoptosis ◽  
Tnf Α ◽  
Wide Range ◽  
Allogeneic Lymphocytes

Abstract Fas (CD95) is a death receptor involved in apoptosis induction on engagement by Fas ligand (CD95L). Although CD95L-mediated apoptosis has been proposed as a pathogenic mechanism in a wide range of diseases, including graft-versus-host disease, systemic CD95 engagement in mice by agonistic CD95-specific antibodies or by soluble multimeric CD95L (smCD95L), though lethal, has been reported to cause apoptosis only in a limited range of cell types, that is, hepatocytes, hepatic sinusoidal endothelial cells, and lymphocytes. Another member of the tumor necrosis factor (TNF)/CD95L family, TNF-α, induces disseminated vascular endothelial cell apoptosis, which precedes apoptosis of other cell types and lethal multiorgan failure. Here we show that systemic CD95 engagement in vivo by agonistic CD95-specific antibody or smCD95L causes rapid, extensive, and disseminated endothelial cell apoptosis throughout the body, by a mechanism that does not depend on TNF-α. Disseminated endothelial cell apoptosis was also the first detectable lesion in a murine model of acute tissue damage induced by systemic transfer of allogeneic lymphocytes and did not occur when allogeneic lymphocytes were from CD95L-defective mice. Both vascular and additional tissue lesions induced by agonistic CD95-specific antibody, smCD95L, or allogeneic lymphocytes were prevented by treatment with an inhibitor of caspase-8, the upstream caspase coupled to CD95 death signaling. Vascular lesions are likely to play an important role in the pathogenesis of allogeneic immune responses and of other diseases involving circulating CD95L-expressing cells or smCD95L, and the prevention of CD95-mediated death signaling in endothelial cells may have therapeutic implications in these diseases.

Abstract 2331: BRCA1 Limits Inflammation Induced Apoptosis And Improves Endothelial Function: A Novel Role Of DNA Repair Genes In Vascular Homeostasis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Krishna K Singh ◽  
Praphulla C Shukla ◽  
Fina Lovren ◽  
Yi Pan ◽  
Paul Jurasz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Dna Repair ◽  
Endothelial Cell ◽  
Endothelial Function ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Brca1 Gene ◽  
Ros Production ◽  
Endothelial Cell Apoptosis ◽  
Induced Apoptosis

INTRODUCTION: Endothelial cell apoptosis, in response to inflammatory, ischemic and hypoxic stressors, has been identified as an essential target for therapies aimed at improving graft patency. BRCA1 is a tumor suppressor gene which functions primarily to promote DNA repair, and afford protection against various genotoxic stimuli, including immunosuppressant and chemotherapeutic regimens often employed post-transplantation. We hypothesized that BRCA1 is a novel target to limit inflammation-induced endothelial cell apoptosis and to restore endothelial function. METHODS AND RESULTS: In the first series of studies, we used a gain-of-function approach by adenoviral BRCA1 overexpression in human umbilical vein endothelial cells (HUVECs). Ad-BRCA1-expressing HUVECs exhibited profound protection against TNFα (20 ng/ml)-induced apoptosis, as assessed by flow cytometry, DNA laddering, COMET assay and cleaved procaspase 3 (P < 0.01). This response was mediated by complete prevention of TNFα-induced increases in endothelial ROS production (P < 0.001, vs. Ad-BRCA1). Furthermore, Ad-BRCA1 overexpression prevented TNFα-induced reduction in key indices of endothelial function, namely capillary-like tube formation (P < 0.01) and cell migration (P < 0.01). The protective effects of BRCA1 were not mediated by changes in total or phosphorylated p53 (P = 0.1) but were associated with a significant 6-fold upregulation in eNOS (P < 0.05). A loss-of-function strategy with BRCA1 gene silencing reversed the effects on endothelial apoptosis, ROS production and eNOS phosporylation. CONCLUSIONS: BRCA1 protects endothelial cells against inflammation-induced apoptosis, through a mechanism that involves up-regulation of eNOS and reduced ROS production, and is a novel candidate gene to limit aberrant vascular remodeling. These data also suggest that patients with BRCA1 mutations or cancer syndromes may be at an exaggerated risk of native and transplant atherosclerosis and graft dysfunction, particularly in the setting of DNA damaging immunosuppressants.

Maternal Anti-HPA-1a Antibodies Increase Endothelial Cell Apoptosis and Permeability

2021 ◽  
pp. 1-9
Author(s):  
Rima Dardik ◽  
Ophira Salomon
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Intracranial Hemorrhage ◽  
Cell Apoptosis ◽  
Endothelial Damage ◽  
Αvβ3 Integrin ◽  
Endothelial Cell Apoptosis ◽  
Vascular Beds ◽  
Alloimmune Thrombocytopenia

Intracranial hemorrhage (ICH) associated with fetal/neonatal alloimmune thrombocytopenia (FNAIT) is attributed mainly to endothelial damage caused by binding of maternal anti-HPA-1a antibodies to the αvβ3 integrin on endothelial cells (ECs). We examined the effect of anti-HPA-1a antibodies on EC function using 2 EC lines from different vascular beds, HMVEC of dermal origin and hCMEC/D3 of cerebral origin. Anti-HPA-1a sera significantly increased apoptosis in both HMVEC and hCMEC/D3 cells and permeability in hCMEC/D3 cells only. This increase in both apoptosis and permeability was significantly inhibited by a monoclonal anti-β3 antibody (SZ21) binding to the HPA-1a epitope. Our results indicate that (1) maternal anti-HPA-1a antibodies impair EC function by increasing apoptosis and permeability and (2) ECs from different vascular beds vary in their susceptibility to pathological effects elicited by maternal anti-HPA-1a antibodies on EC permeability. Examination of maternal anti-HPA-1a antibodies for their effect on EC permeability may predict potential ICH associated with FNAIT.

Involvement of Glycogen Synthase Kinase-3β in Palmitate-Induced Human Umbilical Vein Endothelial Cell Apoptosis

2007 ◽  
Vol 44 (5) ◽  
pp. 365-374 ◽  
Author(s):  
Sung-E. Choi ◽  
Yup Kang ◽  
Hyun-Ju Jang ◽  
Ha-Chul Shin ◽  
Hyo-Eun Kim ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Glycogen Synthase ◽  
Umbilical Vein ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Endothelial Cell Apoptosis ◽  
Human Umbilical Vein

scholarly journals LncRNA LUADT1 sponges miR-195 to prevent cardiac endothelial cell apoptosis in sepsis

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Zhimin Zhang ◽  
Mingzhu Lv ◽  
Xiang Wang ◽  
Zheng Zhao ◽  
Daolong Jiang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Critical Role ◽  
Potential Interaction ◽  
Luciferase Reporter ◽  
Endothelial Cell Apoptosis ◽  
Luciferase Activity Assay ◽  
Apoptosis Related Protein

Abstract Background The oncogenic role of the newly identified lncRNA LUADT1 has been revealed in lung adenocarcinoma. It was reported that LUADT1 plays a critical role in multiple human diseases. This study was carried out to investigate the role of LUADT1 in sepsis. Methods Sixty patients with sepsis and sixty healthy volunteers were recruited for this study. Plasma samples were collected from all participants. Human primary coronary artery endothelial cells were also used in this study. The expression of Pim-1, miR-195 and LUADT1 were detected by RT-qPCR. The interaction between miR-195 and LUADT1 was determined by overexpression experiments and luciferase activity assay. Cell apoptosis was detected by flow cytometry. The expression of apoptosis-related protein was detected by Western blotting. Results Bioinformatics analysis revealed the potential interaction between LUADT1 and miR-195, which was confirmed by dual luciferase reporter assay. LUADT1 was downregulated in patients with sepsis. Moreover, LPS treatment downregulated the expression of LUADT1 in primary cardiac endothelial cells. Overexpression of LUADT1 and miR-195 did not affect the expression of each other in primary cardiac endothelial cells. Interestingly, overexpression of LUADT1 was found to upregulate the expression of Pim-1, a target of miR-195. In addition, it was found that overexpression of LUADT1 and Pim-1 reduced the enhancement effects of miR-195 on LPS-induced cardiac endothelial cell apoptosis. Conclusion In summary, LUADT1 may protect cardiac endothelial cells against apoptosis in sepsis by regulating the miR-195/Pim-1 axis.

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