scholarly journals Physiologic cyclic strain stimulates heme oxygenase‐1 gene expression in endothelial cells: role in cell survival and proliferation

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
William Durante ◽  
Xiao‐ming Liu ◽  
Kelly J. Peyton
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Cell Survival ◽  
Heme Oxygenase ◽  
Cyclic Strain ◽  
Heme Oxygenase 1 ◽  
Cell Survival And Proliferation

Tanshinone IIA Induces Heme Oxygenase 1 Expression and Inhibits Cyclic Strain-Induced Interleukin 8 Expression in Vascular Endothelial Cells

2016 ◽  
Vol 44 (02) ◽  
pp. 377-388 ◽  
Author(s):  
Shaowei Zhuang ◽  
Tzu-Hurng Cheng ◽  
Nang-Lang Shih ◽  
Ju-Chi Liu ◽  
Jin-Jer Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Vascular Endothelial Cells ◽  
Salvia Miltiorrhiza ◽  
Cyclic Strain ◽  
Interleukin 8 ◽  
Tanshinone Iia ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Vascular Endothelial

Tanshinone IIA is the main effective component of Salvia miltiorrhiza, known as “Danshen,” which has been used in many therapeutic remedies in traditional Chinese medicine. However, the direct effects of tanshinone IIA on vascular endothelial cells have not yet been fully described. In the present study, we demonstrated that tanshinone IIA increased heme oxygenase-1 (HO-1) expression in human umbilical vein endothelial cells. Western blot analyses and experiments with specific inhibitors indicated tanshinone IIA enhanced HO-1 expression through the activation of phosphoinositide 3-kinase (PI3K)/Akt and the subsequent induction of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation. In addition, tanshinone IIA inhibited cyclic strain induced interleukin-8 (IL-8) expression. HO-1 silencing significantly abrogated the repressive effects of tanshinone IIA on strain-induced IL-8 expression, which suggests HO-1 has a role in mediating the effects of tanshinone IIA. This study reports for the first time that tanshinone IIA inhibits cyclic strain-induced IL-8 expression via the induction of HO-1 in endothelial cells, providing valuable new insight into the molecular pathways that may contribute to the effects of tanshinone IIA.

PECAM-1-dependent heme oxygenase-1 regulation via an Nrf2-mediated pathway in endothelial cells

2014 ◽  
Vol 111 (06) ◽  
pp. 1077-1088 ◽  
Author(s):  
Yarúa Jaimes ◽  
Ananta Paine ◽  
Constanca Figueiredo ◽  
Britta Eiz-Vesper ◽  
Rainer Blasczyk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Chinese Hamster ◽  
Human Neutrophils ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Functional Link

SummaryThe antioxidant enzyme heme oxygenase (HO)-1, which catalyses the first and rate-limiting step of heme degradation, has major anti-inflammatory and immunomodulatory effects via its cell-type-specific functions in the endothelium. In the current study, we investigated whether the key endothelial adhesion and signalling receptor PECAM-1 (CD31) might be involved in the regulation of HO-1 gene expression in human endothelial cells (ECs). To this end PECAM-1 expression was down-regulated in human umbilical vein ECs (HUVECs) by an adenoviral vector-based knockdown approach. PECAM-1 knockdown markedly induced HO-1, but not the constitutive HO isoform HO-2. Nuclear translocation of the transcription factor NF-E2-related factor-2 (Nrf2), which is a master regulator of the inducible antioxidant cell response, and intracellular levels of reactive oxygen species (ROS) were increased in PECAM-1-deficient HUVECs, respectively. PECAM-1-dependent HO-1 regulation was also examined in PECAM-1 over-expressing Chinese hamster ovary and murine L-cells. Endogenous HO-1 gene expression and reporter gene activity of transiently transfected luciferase HO-1 promoter constructs with Nrf2 target sequences were decreased in PECAM-1 over-expressing cells. Moreover, a regulatory role of ROS for HO-1 regulation in these cells is demonstrated by studies with the antioxidant N-acetylcysteine and exogenous hydrogenperoxide. Finally, direct interaction of PECAM-1 with a native complex of its binding partner NB1 (CD177) and serine proteinase 3 (PR3) from human neutrophils, markedly induced HO-1 expression in HUVECs. Taken together, we demonstrate a functional link between HO-1 gene expression and PECAM-1 in human ECs, which might play a critical role in the regulation of inflammation.

scholarly journals Heme Oxygenase-1 at the Nexus of Endothelial Cell Fate Decision Under Oxidative Stress

2021 ◽  
Vol 9 ◽  
Author(s):  
Sindhushree Raghunandan ◽  
Srinivasan Ramachandran ◽  
Eugene Ke ◽  
Yifei Miao ◽  
Ratnesh Lal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Stress Response ◽  
Cell Surface ◽  
Cell Survival ◽  
Cell Fate ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Cell Fate Decisions

Endothelial cells (ECs) form the inner lining of blood vessels and are central to sensing chemical perturbations that can lead to oxidative stress. The degree of stress is correlated with divergent phenotypes such as quiescence, cell death, or senescence. Each possible cell fate is relevant for a different aspect of endothelial function, and hence, the regulation of cell fate decisions is critically important in maintaining vascular health. This study examined the oxidative stress response (OSR) in human ECs at the boundary of cell survival and death through longitudinal measurements, including cellular, gene expression, and perturbation measurements. 0.5 mM hydrogen peroxide (HP) produced significant oxidative stress, placed the cell at this junction, and provided a model to study the effectors of cell fate. The use of systematic perturbations and high-throughput measurements provide insights into multiple regimes of the stress response. Using a systems approach, we decipher molecular mechanisms across these regimes. Significantly, our study shows that heme oxygenase-1 (HMOX1) acts as a gatekeeper of cell fate decisions. Specifically, HP treatment of HMOX1 knockdown cells reversed the gene expression of about 51% of 2,892 differentially expressed genes when treated with HP alone, affecting a variety of cellular processes, including anti-oxidant response, inflammation, DNA injury and repair, cell cycle and growth, mitochondrial stress, metabolic stress, and autophagy. Further analysis revealed that these switched genes were highly enriched in three spatial locations viz., cell surface, mitochondria, and nucleus. In particular, it revealed the novel roles of HMOX1 on cell surface receptors EGFR and IGFR, mitochondrial ETCs (MTND3, MTATP6), and epigenetic regulation through chromatin modifiers (KDM6A, RBBP5, and PPM1D) and long non-coding RNA (lncRNAs) in orchestrating the cell fate at the boundary of cell survival and death. These novel aspects suggest that HMOX1 can influence transcriptional and epigenetic modulations to orchestrate OSR affecting cell fate decisions.

scholarly journals Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survival

2009 ◽  
Vol 297 (4) ◽  
pp. C907-C915 ◽  
Author(s):  
Yong Wei ◽  
Xiao-ming Liu ◽  
Kelly J. Peyton ◽  
Hong Wang ◽  
Fruzsina K. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Mitochondrial Dysfunction ◽  
Heme Oxygenase ◽  
Hypochlorous Acid ◽  
Significant Rise ◽  
Dominant Negative Mutant ◽  
Heme Oxygenase 1

Hypochlorous acid (HOCl) is a unique oxidant generated by the enzyme myeloperoxidase that contributes to endothelial cell dysfunction and death in atherosclerosis. Since myeloperoxidase localizes with heme oxygenase-1 (HO-1) in and around endothelial cells of atherosclerotic lesions, the present study investigated whether there was an interaction between these two enzymes in vascular endothelium. Treatment of human endothelial cells with the myeloperoxidase product HOCl stimulated a concentration- and time-dependent increase in HO-1 protein that resulted in a significant rise in carbon monoxide (CO) production. The induction of HO-1 protein was preceded by a prominent increase in HO-1 mRNA and total and nuclear factor-erythroid 2-related factor 2 (Nrf2). In addition, HOCl induced a significant rise in HO-1 promoter activity that was blocked by mutating the antioxidant response element (ARE) in the promoter or by overexpressing a dominant-negative mutant of Nrf2. The HOCl-mediated induction of Nrf2 or HO-1 was blocked by the glutathione donor N-acetyl-l-cysteine but was unaffected by ascorbic or uric acid. Finally, treatment of endothelial cells with HOCl stimulated mitochondrial dysfunction, caspase-3 activation, and cell death that was potentiated by the HO inhibitor, tin protoporphyrin-IX, or by the knockdown of HO-1, and reversed by the exogenous administration of biliverdin, bilirubin, or CO. These results demonstrate that HOCl induces HO-1 gene transcription via the activation of the Nrf2/ARE pathway to counteract HOCl-mediated mitochondrial dysfunction and cell death. The ability of HOCl to activate HO-1 gene expression may represent a critical adaptive response to maintain endothelial cell viability at sites of vascular inflammation and atherosclerosis.

Abstract P171: Low Concentrations of Aspirin Activate Cytoprotective Signaling Pathway Genes in Human Endothelial Cells: A Gene Expression Profiling Study

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Reena V Kartha ◽  
Belinda W Cheung ◽  
Subbaya Subramanian ◽  
Henning Schröder
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Low Dose ◽  
Expression Profiles ◽  
Fold Change ◽  
Heme Oxygenase 1 ◽  
Human Endothelial Cells ◽  
Dose Aspirin ◽  
Low Dose Aspirin

Low-dose aspirin is recommended for individuals with risk for heart disease and stroke in order to prevent thrombotic occlusive events. In addition to its well-established platelet inhibitory effects, increased expression of the antioxidant heme oxygenase-1 is considered to contribute to cardiovascular protection by aspirin. However little is known about the genome-wide changes in gene expression mediated by aspirin. In order to identify other molecular pathways and targets affected by aspirin, we investigated the global effects of aspirin treatment (3 μM and 100 μM) in vitro in human endothelial cells (Ea.hy 926) using HT-12 bead arrays (Illumina). The filtered genes were further analyzed using Ingenuity Pathway Analysis (IPA) software. We determined the gene expression profiles of endothelial cells treated with aspirin (3 μM and 100 μM) along with vehicle controls. Gene microarray analysis revealed significant upregulation of 134 genes (p <0.005 and >2 fold change) and downregulation of over 100 genes (p <0.005 and ≤0.5 fold change). Interestingly, the pattern of gene expression was similar between the two analyzed concentrations of 3 μM and 100 μM. The majority of upregulated genes were involved in gene expression, transcriptional regulation, cell-to-cell signalling and interaction and encoded transcription factors such as MAP kinases, phosphoinositide-3-kinases and cell cycle regulators (p<0.005). Several components of heterotrimeric G-proteins and G-protein-coupled receptors were also found to be upregulated which can potentially trigger phospholipase C signaling, suggesting an increase in overall intracellular second messenger signaling. In summary, our gene expression analysis suggests that aspirin at low and therapeutically relevant concentrations (3 μM) is effective in triggering cytoprotective signaling pathways some of which play a role in the regulation of heme oxygenase-1. Moreover, our study shows that low-dose aspirin results in altered expression profiles of a variety of genes. Future studies will have to address the biological and clinical relevance of these novel aspirin targets.

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