scholarly journals Linoleyl hydroperoxide transcriptionally upregulates heme oxygenase-1 gene expression in human renal epithelial and aortic endothelial cells.

1998 ◽  
Vol 9 (11) ◽  
pp. 1990-1997
Author(s):  
A Agarwal ◽  
F Shiraishi ◽  
G A Visner ◽  
H S Nick
Keyword(s):  
Endothelial Cells ◽  
Renal Disease ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Oxidized Ldl ◽  
Heme Oxygenase 1 ◽  
Aortic Endothelial Cells ◽  
Mrna Induction ◽  
Aortic Endothelial

Atherogenic lipoproteins such as oxidized LDL are implicated in the pathogenesis of atherosclerosis and renal disease. Fatty acid hydroperoxides and phospholipids such as linoleyl hydroperoxide (LAox or 13-HPODE) and lysophosphatidylcholine (lyso-PC), abundant components of oxidized LDL, mediate the effects of atherogenic lipids. Oxidized LDL has been shown to induce heme oxygenase-1 (HO-1), a microsomal enzyme that is involved in heme detoxification and is a major endogenous source of carbon monoxide. HO-1 is also induced by many other stimuli that shift cellular redox. To identify the constituents and molecular mechanisms of oxidized LDL-mediated HO-1 induction, human renal epithelial cells and aortic endothelial cells were exposed to LAox and lyso-PC. Exposure to LAox (25 microM) showed an approximately 16-fold induction of HO-1 mRNA, whereas exposure to lyso-PC (25 microM) showed only an approximate 2.6-fold increase. Treatment with actinomycin-D (4 microM), a transcriptional inhibitor, as well as nuclear run-on assays, demonstrated that LAox-mediated HO-1 gene induction is dependent on de novo transcription. Cycloheximide did not affect LAox-mediated HO-1 mRNA induction, suggesting that new protein synthesis is not required for transcriptional induction. Transfection of a human HO-1 promoter-reporter gene construct showed that LAox upregulation of HO-1 occurs via mechanisms different from those of known inducers, heme and cadmium. These studies are the first demonstration that LAox induces HO-1 by transcriptional mechanisms and may have implications in the pathogenesis of cell injury in atherosclerosis and progressive renal disease.

scholarly journals A delayed and sustained rise of cytosolic calcium is elicited by oxidized LDL in cultured bovine aortic endothelial cells

FEBS Letters ◽  
1992 ◽  
Vol 299 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Anne Nègre-Salvayre ◽  
Guylène Fitoussi ◽  
Valérie Réaud ◽  
Marie-Thérèse Pieraggi ◽  
Jean-Claude Thiers ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxidized Ldl ◽  
Cytosolic Calcium ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells ◽  
Aortic Endothelial

Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3465-3473 ◽  
Author(s):  
Shane C. McAllister ◽  
Scott G. Hansen ◽  
Rebecca A. Ruhl ◽  
Camilo M. Raggo ◽  
Victor R. DeFilippis ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Kaposi Sarcoma ◽  
Heme Oxygenase 1 ◽  
Spindle Cell Proliferation

Abstract Kaposi sarcoma (KS) is the most common AIDS-associated malignancy and is characterized by angiogenesis and the presence of spindle cells. Kaposi sarcoma-associated herpesvirus (KSHV) is consistently associated with all clinical forms of KS, and in vitro infection of dermal microvascular endothelial cells (DMVECs) with KSHV recapitulates many of the features of KS, including transformation, spindle cell proliferation, and angiogenesis. To study the molecular mechanisms of KSHV pathogenesis, we compared the protein expression profiles of KSHV-infected and uninfected DMVECs. This comparison revealed that heme oxygenase-1 (HO-1), the inducible enzyme responsible for the rate-limiting step in heme catabolism, was up-regulated in infected endothelial cells. Recent evidence suggests that the products of heme catabolism have important roles in endothelial cell biology, including apoptosis and angiogenesis. Here we show that HO-1 mRNA and protein are up-regulated in KSHV-infected cultures. Comparison of oral and cutaneous AIDS-KS tissues with normal tissues revealed that HO-1 mRNA and protein were also up-regulated in vivo. Increased HO-1 enzymatic activity in vitro enhanced proliferation of KSHV-infected DMVECs in the presence of free heme. Treatment with the HO-1 inhibitor chromium mesoporphyrin IX abolished heme-induced proliferation. These data suggest that HO-1 is a potential therapeutic target for KS that warrants further study. (Blood. 2004;103: 3465-3473)

Abstract 611: AP-1 and ETS Family Transcription Factors Co-localize at Enhancers in Human Aortic Endothelial Cells

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Nicholas T Hogan ◽  
Casey E Romanoski ◽  
Michael T Lam ◽  
Christopher K Glass
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
De Novo ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Motif Analysis ◽  
Aortic Endothelial Cells ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

Introduction: Sequence-specific transcription factors bind DNA regulatory elements and play a key role in establishing cellular identity. Studies comparing macrophages to B cells have revealed that small numbers of such collaborative or lineage-determining transcription factors (LDTF) establish distinct enhancers in each cell type. These factors also allow for the binding of signal dependent transcription factors. Here we present data which suggest members of the AP-1, ETS, and STAT transcription factor families serve as collaborative transcriptional regulators in human aortic endothelial cells (HAEC). Hypothesis: We hypothesize that a set of AP-1 and ETS transcription factors collaborate to establish key endothelial cell enhancers. Methods: Working in HAEC, we measured poised and active enhancers using ChIP-seq for the epigenetic histone modifications H3K4me2 and H3K27Ac, performed motif analysis, and measured transcription factor binding for candidate factors. Knockdowns of JUN, ERG, and STAT3 followed by RNA-seq were used to evaluate altered enhancer function and gene targets of candidate factors. Results: Our de novo motif analysis revealed that motifs for ETS and AP-1 transcription factors are highly enriched at HAEC enhancers. ChIP-seq experiments for JUN, JUNB, ERG, and STAT3 showed between 8,000 and 55,000 intergenic peaks for each factor. Together these peaks bind 50% of poised enhancers, with a subset co-localizing at these sites. Gene ontology analysis showed that gene targets of these enhancers are involved in endothelial-specific functions. Further, knockdown of JUN, ERG, and STAT3 resulted in a twofold or greater change in expression of hundreds of HAEC transcripts. Conclusion: The genome-wide pattern of JUN, JUNB, ERG, and STAT3 co-localization at enhancers in HAEC suggests these factors serve as key regulators that collaboratively modulate endothelial-specific gene expression. Further investigation of candidate lineage-determining transcription factors using pro-atherogenic signals could reveal regulatory mechanisms of disease-relevant endothelial transcriptional programs.

scholarly journals Dihydrotestosterone Inhibits Lectin-Like Oxidized-LDL Receptor-1 Expression in Aortic Endothelial Cells via a NF-κB/AP-1-Mediated Mechanism

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3405-3415 ◽  
Author(s):  
Yang Qiu ◽  
Tomoko Tanaka ◽  
Hajime Nawata ◽  
Toshihiko Yanase
Keyword(s):  
Endothelial Cells ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Nuclear Factor Κb ◽  
High Cholesterol Diet ◽  
Sham Operation ◽  
Aortic Endothelial Cells ◽  
Aortic Endothelial

The mechanisms involved in the antiatherosclerotic effects of androgens are unclear. Although lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells plays critical roles in atherosclerosis, the effects of androgens on endothelial LOX-1 expression has not been examined. Therefore, to investigate the effects of dihydrotestosterone (DHT) on LOX-1 expression in rabbit aortic endothelial cells and cultured human aortic endothelial cells (HAEC), pellets containing DHT or placebo were sc implanted into 26 male New Zealand white rabbits at the time of castration or sham operation. The rabbits were then fed a high-cholesterol diet (HCD) for 2 wk. Microscopic examination of the aortic arch revealed that DHT significantly reduced HCD-induced LOX-1 expression in endothelial cells compared with placebo. In cultured HAEC, DHT at concentrations above 10−9 to 10−7 mol/liter inhibited TNFα-induced LOX-1 mRNA and protein expression. Deletion and mutation analysis of human LOX-1 promoter-luciferase constructs transfected into HAEC with an androgen receptor (AR) expression plasmid revealed that the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element (TRE; nucleotides −60/−53) contributed to the inhibitory effects of DHT on TNFα-induced LOX-1 expression. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that TNFα- and TPA-dependent enrichment of p65 and phosphorylated c-Jun in the TRE chromatin region was inhibited by DHT-AR. Consistent with these results, DHT also suppressed TPA-induced expression of LOX-1. In conclusion, DHT exerts antiatherosclerotic effects by suppressing endothelial LOX-1 expression. This effect is partly mediated by the suppression of nuclear factor-κB- and activator protein 1-dependent activation of the LOX-1 promoter.

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