scholarly journals Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1007
Author(s):  
Qiaojian Yan ◽  
Zhimin Mao ◽  
Jingru Hong ◽  
Kun Gao ◽  
Manabu Niimi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cell Injury ◽  
Tanshinone Iia ◽  
Camp Signaling ◽  
Endothelial Cell Injury ◽  
Creb Phosphorylation ◽  
Camp Signaling Pathway ◽  
Injury Model

Tanshinone IIA (Tan IIA), an active ingredient of Danshen, is a well-used drug to treat cardiovascular diseases. Currently, the mechanisms involved remain poorly understood. Given that many actions of Tan IIA could be similarly achieved by hydrogen sulfide (H2S), we speculated that Tan IIA might work through the induction of endogenous H2S. This study was to test this hypothesis. Exposure to endothelial cells to Tan IIA elevated H2S-synthesizing enzyme cystathionine γ-Lyase (CSE), associated with an increased level of endogenous H2S and free thiol activity. Further analysis revealed that this effect of Tan IIA was mediated by an estrogen receptor (ER) and cAMP signaling pathway. It stimulated VASP and CREB phosphorylation. Inhibition of ER or PKA abolished the CSE-elevating effect, whereas activation of ER or PKA mimicked the effect of Tan IIA. In an oxidative endothelial cell injury model, Tan IIA potently attenuated oxidative stress and inhibited cell death. In support of a role of endogenous H2S, inhibition of CSE aggerated oxidative cell injury. On the contrary, supplement of H2S attenuated cell injury. Collectively, our study characterized endogenous H2S as a novel mediator underlying the pharmacological actions of Tan IIA. Given the multifaceted functions of H2S, the H2S-stimulating property of Tan IIA could be exploited for treating many diseases.

scholarly journals Cytoprotective effects of adrenomedullin in glomerular cell injury: Central role of cAMP signaling pathway

1997 ◽  
Vol 52 (4) ◽  
pp. 917-925 ◽  
Author(s):  
Eduardo N. Chini ◽  
Claudia C.S. Chini ◽  
Chad Bolliger ◽  
Michihisa Jougasaki ◽  
Joseph P. Grande ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Injury ◽  
Camp Signaling ◽  
Glomerular Cell ◽  
Camp Signaling Pathway

scholarly journals The Role of MicroRNA-155 in Glomerular Endothelial Cell Injury of Diabetic Nephropathy

2021 ◽  
Author(s):  
Kaiying He ◽  
Zhan Chen ◽  
Jing Zhao ◽  
Yang He ◽  
Rongrong Deng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
High Glucose ◽  
Cell Injury ◽  
Inflammatory Factors ◽  
Glucose Stimulation ◽  
Endothelial Cell Injury ◽  
Glomerular Endothelial Cells ◽  
Human Glomerular Endothelial Cells

Abstract Objective: To investigate the role of microRNA-155-5p (miR-155-5p) on apoptosis and inflammatory response in human glomerular endothelial cells (HRGEC) cultured with high glucose.Methods: The primary human glomerular endothelial cells (HRGEC) were studied, QPCR, WB , IF were used to detect cell morphology, target gene ETS-1 (ETS-1), downstream factors VCAM-1 and MCP-1, and apoptosis of cells in each group after high glucose stimulation and transfection with miR-155 overexpression or inhibitor.Results:1.The expression of inflammatory factors and apoptosis of HRGEC cells increased under high glucose stimulation.2.The overexpression of miR-155 in HRGEC cells under high glucose stimulation decreased the expression of ETS-1, while the expression of ETS-1 increased when miR-155 was inhibited. These results suggest that miR-155 may be involved in endothelial cell injury by negatively regulating the expression of ETS-1.3.HRGEC cells were transfected with miR-155 mimic and ETS-1 siRNA with high glucose stimulation. The expression of ETS-1 was positively correlated with the expression of downstream factors VCAM-1 and MCP-1. These results suggest that ETS-1 can mediate endothelial cell inflammation by regulating VCAM-1 and MCP-1.

Activation of nuclear factor erythroid 2-related factor 2 and PPARγ plays a role in the genistein-mediated attenuation of oxidative stress-induced endothelial cell injury

2012 ◽  
Vol 109 (2) ◽  
pp. 223-235 ◽  
Author(s):  
Ting Zhang ◽  
Fan Wang ◽  
Hong-Xia Xu ◽  
Long Yi ◽  
Yu Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Viability ◽  
Cell Injury ◽  
B Cell Lymphoma ◽  
Related Factor ◽  
Nuclear Factor ◽  
Antioxidant Genes ◽  
Endothelial Cell Injury

We investigate the cytoprotective effects and the molecular mechanism of genistein in oxidative stress-induced injury using an endothelial cell line (EA.hy926). An oxidative stress model was established by incubating endothelial cells with H2O2. According to the present results, genistein pretreatment protected endothelial cells against H2O2-induced decreases in cell viability and increases in apoptosis. Genistein also prevented the inhibition of B-cell lymphoma 2 and the activation of caspase-3 induced by H2O2. Genistein increased superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels and attenuated the decrease in these antioxidants during oxidative stress. We also found that genistein induced the promoter activity of both nuclear factor erythroid 2-related factor 2 (Nrf2) and PPARγ. Additionally, genistein induced the nuclear translocation of Nrf2 and PPARγ. While genistein caused the up-regulation of both Nrf2 and PPARγ, it also activated and up-regulated the protein expression and transcription of a downstream protein, haem oxygenase-1 (HO-1). Moreover, the use of Nrf2 small interfering RNA transfection and HO-1- or PPARγ-specific antagonists (Znpp and GW9662, respectively) blocked the protective effects of genistein on endothelial cell viability during oxidative stress. Therefore, we conclude that oxidative stress-induced endothelial cell injury can be attenuated by treatment with genistein, which functions via the regulation of the Nrf2 and PPARγ signalling pathway. Additionally, the endogenous antioxidants SOD, CAT and GSH appear to play a role in the antioxidant activity of genistein. The present findings suggest that the beneficial effects of genistein involving the activation of cytoprotective antioxidant genes may represent a novel strategy in the prevention and treatment of cardiovascular endothelial damage.

Anoxia-reoxygenation-induced, neutrophil-mediated endothelial cell injury: role of elastase

1990 ◽  
Vol 259 (3) ◽  
pp. H925-H931 ◽  
Author(s):  
W. Inauen ◽  
D. N. Granger ◽  
C. J. Meininger ◽  
M. E. Schelling ◽  
H. J. Granger ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Injury ◽  
Cell Detachment ◽  
51Cr Release ◽  
Microvascular Endothelium ◽  
Endothelial Cell Injury ◽  
Cell Dysfunction ◽  
Neutrophilic Elastase

The aim of this study was to assess the role of neutrophilic elastase in anoxia-reoxygenation-induced, neutrophil-mediated injury to microvascular endothelium. Cultured bovine microvascular endothelial cells were grown to confluence and labeled with 51Cr. The endothelial cells were exposed to a 30-min period of anoxia and subsequently reoxygenated. Endothelial cell injury, quantitated as 51Cr release and cell detachment, was determined 8 h after reoxygenation. Addition of neutrophils upon reoxygenation enhanced the anoxia-reoxygenation-induced increase in 51Cr release and cell detachment. The neutrophil-mediated injury was associated with elastase release from the neutrophils. Four agents were used to inhibit neutrophilic elastase activity: Eglin C, methoxysuccunyl-Ala2-Pro-Val-CH2Cl, L658,758, and a monoclonal antibody against neutrophilic elastase. All elastase inhibitors attenuated the neutrophil-mediated endothelial cell detachment but not 51Cr release. Addition of purified human neutrophilic elastase, at a level that mimicked the release from neutrophils, increased cell detachment in endothelial cells exposed to anoxia-reoxygenation but did not affect 51Cr release. Our results indicate that elastase plays an important role in anoxia-reoxygenation-induced, neutrophil-mediated endothelial cell dysfunction.

Role of oxidative stress in vinorelbine-induced vascular endothelial cell injury

2010 ◽  
Vol 48 (1) ◽  
pp. 120-127 ◽  
Author(s):  
Takaaki Yamada ◽  
Nobuaki Egashira ◽  
Maiko Imuta ◽  
Takahisa Yano ◽  
Yui Yamauchi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Cell Injury ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Injury

Cytosolic free Ca2+ and proteolysis in lethal oxidative injury in endothelial cells

1991 ◽  
Vol 261 (5) ◽  
pp. C889-C896 ◽  
Author(s):  
M. D. Geeraerts ◽  
M. F. Ronveaux-Dupal ◽  
J. J. Lemasters ◽  
B. Herman
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Viability ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rapid Onset ◽  
Acetoxymethyl Ester ◽  
Endothelial Cell Injury

Oxygen free radicals (OFR) are thought to mediate ischemia-reperfusion injury to endothelium of heart, lung, brain, liver, and kidney and contribute to development of atherosclerosis, pulmonary O2 toxicity, and adult respiratory distress syndrome. Increased cytosolic free Ca2+ (Cai2+) has been proposed as a mechanism of injury from oxidative stress, yet the pathways by which an increase in Cai2+ may cause OFR-mediated endothelial cell injury remain unknown. Using multiparameter digitized video microscopy and the fluorescent probes, fura-2 acetoxymethyl ester and propidium iodide, we measured Cai2+ and cell viability in human umbilical endothelial cells during oxidative stress with xanthine (50 microM) plus xanthine oxidase (40 mU/ml). Oxidative stress caused a sustained increase in Cai2+ from a resting level of 90-100 nM to near 500 nM, which was preceded by formation of plasma membrane blebs. The increase in Cai2+ was prevented by removal of extracellular Ca2+ (Cao2+). Prevention of the increase in Cai2+ was associated with prolonged cell viability. Readdition of Cao2+ resulted in an immediate large increase in Cai2+ and rapid onset of cell death. The protease inhibitors, leupeptin and pepstatin, delayed the increase in Cai2+ and prolonged cell viability. The results are consistent with the hypothesis that endothelial cell injury due to oxidative stress may be the result of Cai2+ influx and resultant activation of Ca(2+)-dependent proteases.

scholarly journals Endothelial Cells Caught in the Crosshairs of Pulmonary Arterial Hypertension

2010 ◽  
Vol 9 (3) ◽  
pp. 156-158
Author(s):  
Duncan J. Stewart
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Cell Injury ◽  
Endothelial Cell Injury ◽  
Pulmonary Arterial

The purpose of this overview is to provide a framework for understanding the fundamental mechanisms underlying the initiation and progression of pulmonary arterial hypertension and suggest a unifying concept that may better guide the development of therapies based on the central role of endothelial cell injury and loss by apoptosis.

scholarly journals Diabetes Promotes Retinal Vascular Endothelial Cell Injury by Inducing CCN1 Expression

2021 ◽  
Vol 8 ◽  
Author(s):  
Haicheng Li ◽  
Ting Li ◽  
Heting Wang ◽  
Xuemin He ◽  
Ying Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Endothelial Cell ◽  
Tight Junction ◽  
Cell Injury ◽  
Cell Physiology ◽  
Sequencing Analysis ◽  
Vascular Endothelial ◽  
Endothelial Cell Injury

Purpose: Diabetic retinopathy (DR) is one of the most common diabetic microvascular complications. However, the pathogenesis of DR has not yet been fully elucidated. This study aimed to discover novel and key molecules involved in the pathogenesis of DR, which could potentially be targets for therapeutic DR intervention.Methods: To identify potential genes involved in the pathogenesis of DR, we analyzed the public database of neovascular membranes (NVMs) from patients with proliferative diabetic retinopathy (PDR) and healthy controls (HCs) (GSE102485, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102485). Further, we compared these findings by performing RNA-sequencing analysis of peripheral blood mononuclear cells (PBMC) from patients with DR, control patients with non-complicated diabetes mellitus (DMC), and HCs. To determine the critical role of candidate genes in DR, knockdown or knockout was performed in human retinal vascular endothelial cells (HRVECs). The oxidative stress pathway, as well as tight junction integrity, was analyzed.Results: Transcriptional profiles showed distinct patterns between the NVMs of patients with DR and those of the HCs. Those genes enriched in either extracellular matrix (ECM)-receptor interaction or focal adhesion pathways were considerably upregulated. Both pathways were important for maintaining the integrity of retinal vascular structure and function. Importantly, the gene encoding the matricellular protein CCN1, a key gene in cell physiology, was differentially expressed in both pathways. Knockdown of CCN1 by small interfering RNA (siRNA) or knockout of CCN1 by the CRISPR-Cas9 technique in HRVECs significantly increased the levels of VE-cadherin, reduced the level of NADPH oxidase 4 (NOX4), and inhibited the generation of reactive oxygen species (ROS).Conclusion: The present study identifies CCN1 as an important regulator in the pathogenesis of DR. Increased expression of CCN1 stimulates oxidative stress and disrupts tight junction integrity in endothelial cells by inducing NOX4. Thus, targeting the CCN1/NOX4 axis provides a therapeutic strategy for treating DR by alleviating endothelial cell injury.

scholarly journals Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells

2012 ◽  
Vol 302 (6) ◽  
pp. C839-C852 ◽  
Author(s):  
Wei P. Feinstein ◽  
Bing Zhu ◽  
Silas J. Leavesley ◽  
Sarah L. Sayner ◽  
Thomas C. Rich
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Microvascular Endothelial Cells ◽  
Camp Production ◽  
Barrier Integrity ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Camp Signaling Pathway ◽  
Microvascular Endothelial

Cyclic AMP signals encode information required to differentially regulate a wide variety of cellular responses; yet it is not well understood how information is encrypted within these signals. An emerging concept is that compartmentalization underlies specificity within the cAMP signaling pathway. This concept is based on a series of observations indicating that cAMP levels are distinct in different regions of the cell. One such observation is that cAMP production at the plasma membrane increases pulmonary microvascular endothelial barrier integrity, whereas cAMP production in the cytosol disrupts barrier integrity. To better understand how cAMP signals might be compartmentalized, we have developed mathematical models in which cellular geometry as well as total adenylyl cyclase and phosphodiesterase activities were constrained to approximate values measured in pulmonary microvascular endothelial cells. These simulations suggest that the subcellular localizations of adenylyl cyclase and phosphodiesterase activities are by themselves insufficient to generate physiologically relevant cAMP gradients. Thus, the assembly of adenylyl cyclase, phosphodiesterase, and protein kinase A onto protein scaffolds is by itself unlikely to ensure signal specificity. Rather, our simulations suggest that reductions in the effective cAMP diffusion coefficient may facilitate the formation of substantial cAMP gradients. We conclude that reductions in the effective rate of cAMP diffusion due to buffers, structural impediments, and local changes in viscosity greatly facilitate the ability of signaling complexes to impart specificity within the cAMP signaling pathway.

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