Critical Role of Lipid Raft Redox Signaling Platforms in Endostatin-Induced Coronary Endothelial Dysfunction

Jin, Si; Zhang, Yang; Li, Pin‐Lan

doi:10.1161/atvbaha.107.159772

Cited by 61 publications

(101 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The siRNA of ASM gene was purchased from QIAGEN, which has been proven to be efficient to knock down the ASM gene in CAECs by our laboratory's previous studies (20,40) and was further confirmed in the present study (Supplemental Fig. 1).…”

Section: Immunofluorescent Microscopic Analysis Of Lr Clusterssupporting

confidence: 76%

Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries

Bao

Xia

Poklis

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

The present study determined whether activation of acid sphingomyelinase (ASM) drives membrane proximal lysosomes to fuse to the cell surface, facilitating membrane lipid rafts (LRs) clustering in coronary arterial endothelial cells (CAECs) and leading to endothelial dysfunction. By confocal microscopy, the activators of ASM, phosphatidylinositol (PI), and bis (monoacylglyceryl) phosphate (Bis), and an inducer of ASM, butyrate, were found to increase LRs clustering in bovine CAECs, which was blocked by lysosome fusion inhibitor vacuolin-1. However, arsenic trioxide (Ars), an inducer of de novo synthesis of ceramide, had no such effect. Similarly, vacuolin-1-blockable effects were observed using fluorescence resonance energy transfer detection. Liquid chromatography-electrospray ionization-tandem mass spectrometry analysis demonstrated that all of these treatments, even Ars, increased ceramide production in CAECs. When ASM gene was silenced, all treatments except Ars no longer increased ceramide levels. Furthermore, dynamic fluorescence monitoring in live cells showed that PI and Bis stimulated lysosome-membrane fusion in CAECs. Functionally, PI and Bis impaired endothelium-dependent vasodilation in perfused coronary arteries, which was blocked by vacuolin-1 and a lysosome function inhibitor, bafilomycine. FasL (Fas ligand), a previously confirmed lysosome fusion stimulator as a comparison, also produced a similar effect. It is concluded that ASM activation serves as a triggering mechanism and driving force, leading to fusion of membrane proximal lysosomes into LR clusters on the cell membrane of CAECs, which represents a novel mechanism mediating endothelial dysfunction during death receptor activation or other pathological situation.

show abstract

Section: Immunofluorescent Microscopic Analysis Of Lr Clusterssupporting

confidence: 76%

Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries

Bao

Xia

Poklis

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous studies have demonstrated that the formation of MR-redox signaling platforms in the EC membrane is associated with ceramide production via lysosomal ASM, which is translocated to the plasma membrane via membrane proximal lysosome trafficking and fusion after stimulation (Jin et al, 2008b;Bao et al, 2010a,b). Ceramides spontaneously fuse MRs into large ceramide-enriched membrane domains, which can serve as MR-redox signaling platforms (Zhang et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Attenuation by Statins of Membrane Raft-Redox Signaling in Coronary Arterial Endothelium

Xiong

et al. 2013

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Membrane raft (MR)-redox signaling platforms associated with NADPH oxidase are involved in coronary endothelial dysfunction. Here, we studied whether statins interfere with the formation of MR-redox signaling platforms to protect the coronary arterial endothelium from oxidized low-density lipoprotein (OxLDL)-induced injury and from acute hypercholesterolemia. In cultured human coronary arterial endothelial cells, confocal microscopy detected the formation of an MRs clustering when they were exposed to OxLDL, and such MR platform formation was inhibited markedly by statins, including pravastatin and simvastatin. In these MR clusters, NADPH oxidase subunits gp91 phox and p47 phox were aggregated and were markedly blocked by both statins. In addition, colocalization of acid sphingomyelinase (ASM) and ceramide was induced by OxLDL, which was blocked by statins. Electron spin resonance spectrometry showed that OxLDL-induced superoxide (O 2 .2 ) production in the MR fractions was substantially reduced by statins. In coronary artery intima of mice with acute hypercholesterolemia, confocal microscopy revealed a colocalization of gp91 phox , p47 phox , ASM, or ceramide in MR clusters. Such colocalization was rarely observed in the arteries of normal mice or significantly reduced by pretreatment of hypercholesterolemic mice with statins. Furthermore, O 2 .2 production in situ was 3-fold higher in the coronary arteries from hypercholesterolemic mice than in those from normal mice, and such increase was inhibited by statins. Our results indicate that blockade of MR-redox signaling platform formation in endothelial cell membrane may be another important therapeutic mechanism of statins in preventing endothelial injury and atherosclerosis and may be associated with their direct action on membrane cholesterol structure and function.

show abstract

“…When cells were grown to ϳ70 -80% confluence, human recombinant TNF-␣ (PeproTech, Rocky Hill, NJ) was added to the medium in a final concentration of 20 ng/ml for 15 min in the presence or absence of MCD (10 mmol/l; Sigma, St. Louis, MO), desipramine (DES, 10 M, Sigma), apocynin (Apo, 3 M, Sigma), or diphenyleneiodonium (DPI, 1 M, Sigma). Doses of compounds used in these experiments were based on our previous studies and some preliminary data showing that they could effectively inhibit corresponding cell responses (13,22,38,50).…”

Section: Methodsmentioning

confidence: 99%

“…The procedures for Western blot analysis were described in detail in our previous publications (22,49). For immunodetection of LR-associated proteins, 50 l of resuspended proteins were subjected to SDS-PAGE, transferred onto a nitrocellulose membrane, and blocked as described previously (50).…”

Section: Methodsmentioning

confidence: 99%

“…Membrane LRs are able to form relatively larger macrodomains or platforms upon activation of individual receptors by ligand binding, where various signaling molecules can be recruited and aggregated to form signaling platforms or signalosomes (11,51), activating various signaling pathways (23,28,46). One of such signaling platforms was named as the LR redox signaling platform (22,50), which is recognized as a missing link between death receptors and NOX activation in endothelial cells (46). It was also demonstrated that the formation of LR signaling platforms is associated with ceramide production by hydrolysis of sphingomyelin via acid sphingomyelinase (ASMase) (2,20,21,49).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Lipid raft-dependent activation of dual oxidase 1/H₂O₂/NF-κB pathway in bronchial epithelial cells

Wang

Zhen

Yao

et al. 2011

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

The present study addressed whether dual oxidase 1 (Duox1), a predominant isoform of NADPH oxidase in bronchial epithelial cells, is also activated through assembling of Duox1 and its partners such as p47 phox due to lipid raft (LR) clustering. By gradient ultracentrifugation to isolate LR fractions in bronchial epithelial cells, it was found that Duox1 or p47 phox was translocated into LR fractions when stimulated by tumor necrosis factor-α (TNF-α). Confocal microscopic analysis revealed that LRs were aggregated or clustered in the membrane, which were colocalized with Duox1 or p47 phox. Ceramide, a hydrolysis product of sphingomyelin, was also found colocalized with Duox1 or p47 phox upon stimulation. In the presence of the commonly used LR disruptor, methyl-β-cyclodextrin (MCD), or the acid sphingomyelinase (ASMase) inhibitor, desipramine (DES), TNF-α-stimulated aggregation, translocation, and colocalization of LR components and Duox1 or its partners was abolished. Functionally, TNF-α-stimulated H2O2 production was also blocked by MCD and DES (194.6 ± 15.4% vs. 90.6 ± 15.9% and 148.8 ± 20.4%), and the activation of the pivotal proinflammatory transcription factor, NF-κB, by TNF-α was reversed by MCD and DES as well as by small interfering RNAs of Duox1 or ASMase. Our results for the first time demonstrate that Duox1-mediated redox signaling in bronchial epithelial cells is associated with LR clustering dependent on the production of ceramide through ASMase.

show abstract

Critical Role of Lipid Raft Redox Signaling Platforms in Endostatin-Induced Coronary Endothelial Dysfunction

Cited by 61 publications

References 44 publications

Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries

Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries

Attenuation by Statins of Membrane Raft-Redox Signaling in Coronary Arterial Endothelium

Lipid raft-dependent activation of dual oxidase 1/H₂O₂/NF-κB pathway in bronchial epithelial cells

Contact Info

Product

Resources

About

Critical Role of Lipid Raft Redox Signaling Platforms in Endostatin-Induced Coronary Endothelial Dysfunction

Cited by 61 publications

References 44 publications

Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries

Triggering role of acid sphingomyelinase in endothelial lysosome-membrane fusion and dysfunction in coronary arteries

Attenuation by Statins of Membrane Raft-Redox Signaling in Coronary Arterial Endothelium

Lipid raft-dependent activation of dual oxidase 1/H2O2/NF-κB pathway in bronchial epithelial cells

Contact Info

Product

Resources

About

Lipid raft-dependent activation of dual oxidase 1/H₂O₂/NF-κB pathway in bronchial epithelial cells