scholarly journals Atheroprotective action of a modified organoselenium compound: in vitro evidence

2016 ◽  
Vol 88 (3 suppl) ◽  
pp. 1953-1965 ◽  
Author(s):  
JADE DE OLIVEIRA ◽  
MARCOS R. STRALIOTTO ◽  
GIANNI MANCINI ◽  
CLAUDIA P. FIGUEIREDO ◽  
ANTÔNIO L. BRAGA ◽  
...  
Keyword(s):  
Foam Cell ◽  
Oxidized Ldl ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Organoselenium Compound ◽  
Organoselenium Compounds ◽  
Concentration Dependent Manner

ABSTRACT Oxidation of low-density lipoprotein (LDL) has been strongly suggested to play a significant role in the pathogenesis of atherosclerosis. Thus, reducing LDL oxidation is a potential approach to decrease the risk of the atherosclerosis. Organoselenium compounds have demonstrated promising atheroprotective properties in experimental models. Herein, we tested the in vitro atheroprotective capability of a modified organoselenium compound, Compound HBD, in protecting isolated LDL from oxidation as well as foam cells formation. Moreover, the glutathione peroxidase (GPx)-like activity of Compound HBD was analyzed in order to explore the mechanisms related to the above-mentioned protective effects. The Compound HBD in a concentration-dependent manner reduced the Cu2+-induced formation of conjugated dienes. The protein portion from LDL were also protected from Cu2+-induced oxidation. Furthermore, the Compound HBD efficiently decreased the foam cell formation in J774 macrophage cells exposed to oxidized LDL. We found that the atheroprotective effects of this compound can be, at least in part, related to its GPx-like activity. Our findings demonstrated an impressive effect of Compound HBD against LDL-induced toxicity, a further in vivo study to investigate in more detail the antioxidant and antiatherogenic effects of this compound could be considered.

Abstract 451: HPODE Upregulates the Expression of Secretory Phospholipase A2 Group IIA in Rat Smooth Muscle Cells. Potential Contribution to the Progression of Atherosclerosis

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Zhaohui Yang ◽  
Chandrakala Aluganti Narasimhulu ◽  
Xueting Jiang ◽  
Sampath Parthasarathy
Keyword(s):  
Phospholipase A2 ◽  
Foam Cell ◽  
Oxidized Ldl ◽  
Foam Cell Formation ◽  
Potential Contribution ◽  
Dependent Manner ◽  
Secretory Phospholipase A2 ◽  
Concentration Dependent Manner ◽  
Decomposition Products ◽  
Secretory Phospholipase

Introduction Peroxidized lipids have been suggested to contribute to atherosclerosis in a number of ways. Accumulating evidence indicates that Group IIA secretory phospholipase A2 (sPLA2-IIA) may contribute to the atherogenic process and serve as markers for cardiovascular diseases. However, the relationship between lipid peroxides and sPLA2-IIA remain poorly identified. Hypothesis Peroxidized lipids such as HPODEs might induce the expression of sPLA2-IIA and enhance the uptake of LDL, thereby contributing to lipid accumulation. Methods Different concentrations of HPODE (0 μM, 12.5μM, 25μM) or oxidized -LDL (ox-LDL) (25μg/ml) were incubated with SMCs at 37°C. Real-time PCR was used to assay gene expression. The degradation of HPODE and ox-LDL was also monitored by the loss of peroxides and conjugated dienes. The formation of HPODE decomposition products was followed by electrospray mass spectrometry. Results Incubation of SMCs with HPODE resulted in an up-regulation of sPLA2-IIA mRNA expression in a concentration dependent manner. However, ox-LDL had limited or no effects in the expression of sPLA2. In addition, SMCs and peritoneal mouse macrophages pretreated with HPODE for 8hrs followed by DiI-LDL (20μg/ml) showed an increase in accumulation of labeled LDL as compared to control. We also noted that HPODE was decomposed by SMCs in hours as compared to no cell incubations. However, incubation of peroxidized lipids in the form of ox-LDL resulted in poor decomposition of the peroxides. Conclusion SMCs may break down the peroxidized fatty acids leading to the formation of simple compounds such as aldehydes and carboxylic acids. HPODE or its decomposition products may induce the expression of sPLA2-II and enhance foam cell formation.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

Properties of neuroprotective cell-permeant Ca2+ chelators: effects on [Ca2+]i and glutamate neurotoxicity in vitro

1994 ◽  
Vol 72 (4) ◽  
pp. 1973-1992 ◽  
Author(s):  
M. Tymianski ◽  
M. P. Charlton ◽  
P. L. Carlen ◽  
C. H. Tator
Keyword(s):  
Time Course ◽  
Dependent Manner ◽  
Protective Effects ◽  
Tetraacetic Acid ◽  
Acetoxymethyl Ester ◽  
Neuroprotective Effects ◽  
Concentration Dependent Manner ◽  
Fura 2 ◽  
Glutamate Neurotoxicity

1. Cell-permeant Ca2+ chelators such as 1,2-bis-(2-amino-phenoxy)ethane- N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) protect neurons against excitotoxic and ischemic neuronal injury in vitro and in vivo. Here we provide the first steps toward characterizing the mechanisms by which these agents produce their neuroprotective effects. 2. Cultured mouse spinal neurons were simultaneously loaded with the Ca2+ indicator fura-2 and with one of three permeant chelators derived from the fast Ca2+ buffer BAPTA, or with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Adding these chelators did not interfere with the fluorescence spectrum of fura-2 and had no effect on baseline [Ca2+]i. 3. The neurons were challenged with 250 microM L-glutamate for 50 min, producing a marked transient [Ca2+]i increase followed by a decay of [Ca2+]i to a lower “plateau.” About 80% of control neurons succumbed to this excitotoxic insult. Neurons that survived adjusted their plateau [Ca2+]i to lower levels than those that succumbed. 4. Neurons that were pretreated with permeant Ca2+ chelators became more resistant to these neurotoxic challenges. 5. We examined whether this reduction in glutamate neurotoxicity could be related to the given buffer's known Ca2+ affinity (Kd), its Ca2+ binding kinetics, and its ability to attenuate glutamate-induced [Ca2+]i increases. 6. Pretreatment of neurons with BAPTA analogues having Kds ranging from 100 to 3,600 microM 1) attenuated the amplitude and 2) lengthened the time constant describing the rise and decay of the glutamate-evoked [Ca2+]i transient. The magnitude of these effects paralleled the affinity of the chelator for Ca2+. 7. BAPTA-AM and its analogues dramatically attenuated the early neurotoxicity of glutamate, reducing cell deaths by up to 80%. However, in contrast with the graded effects of chelators having different Ca2+ affinities on Ca2+ transients, all BAPTA analogues were equally protective. These protective effects did not relate to the chelators' Ca2+ affinity within a Kd range of 100 nM (for BAPTA) to 3,600 nM (for 5,5'-dibromo BAPTA). 8. BAPTA-AM protected neurons in a concentration-dependent manner with 50% protection obtained with 10 microM, a concentration having no effect on the [Ca2+]i transient amplitude. 9. EGTA, a slow Ca2+ buffer with a similar Ca2+ affinity to BAPTA produced the same effects as BAPTA on [Ca2+]i transient kinetics. However, it was far less protective than BAPTA. 10. The time course of early glutamate neurotoxicity was altered by the BAPTA analogues, but not EGTA. BAPTA analogues caused a small increase in cell deaths in the first minutes of each experiment, followed by relative sparing from further neurodegeneration. 11. The ability of low Ca2+ affinity chelators such as 5,5'-dibromo BAPTA to protect neurons without markedly attenuating measured [Ca2+]i increases conflicts with the hypothesis that global elevations in [Ca2+]i are responsible for triggering neurotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Anti-Atherosclerotic Activity of (3R)-5-Hydroxymellein from an Endophytic Fungus Neofusicoccum parvum JS-0968 Derived from Vitex rotundifolia through the Inhibition of Lipoproteins Oxidation and Foam Cell Formation

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 715
Author(s):  
Jae-Yong Kim ◽  
Soonok Kim ◽  
Sang Hee Shim
Keyword(s):  
Conformational Changes ◽  
Endophytic Fungus ◽  
Foam Cell ◽  
Oxidized Ldl ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Neofusicoccum Parvum

An endophytic fungus, Neofusicoccum parvum JS-0968, was isolated from a plant, Vitex rotundifolia. The chemical investigation of its cultures led to the isolation of a secondary metabolite, (3R)-5-hydroxymellein. It has been reported to have antifungal, antibacterial, and antioxidant activity, but there have been no previous reports on the effects of (3R)-5-hydroxymellein on atherosclerosis. The oxidation of lipoproteins and foam cell formation have been known to be significant in the development of atherosclerosis. Therefore, we investigated the inhibitory effects of (3R)-5-hydroxymellein on atherosclerosis through low-density lipoprotein (LDL) and high-density lipoprotein (HDL) oxidation and macrophage foam cell formation. LDL and HDL oxidation were determined by measuring the production of conjugated dienes and malondialdehyde, the amount of hyperchromicity and carbonyl content, conformational changes, and anti-LDL oxidation. In addition, the inhibition of foam cell formation was measured by Oil red O staining. As a result, (3R)-5-hydroxymellein suppressed the oxidation of LDL and HDL through the inhibition of lipid peroxidation, the decrease of negative charges, the reduction of hyperchromicity and carbonyl contents, and the prevention of apolipoprotein A-I (ApoA-I) aggregation and apoB-100 fragmentation. Furthermore, (3R)-5-hydroxymellein significantly reduced foam cell formation induced by oxidized LDL (oxLDL). Taken together, our data show that (3R)-5-hydroxymellein could be a potential preventive agent for atherosclerosis via obvious anti-LDL and HDL oxidation and the inhibition of foam cell formation.

Protective Effects on Mitochondria and Anti-Aging Activity of Polysaccharides from Cultivated Fruiting Bodies of Cordyceps militaris

2010 ◽  
Vol 38 (06) ◽  
pp. 1093-1106 ◽  
Author(s):  
Xing-Tai Li ◽  
Hong-Cheng Li ◽  
Chun-Bin Li ◽  
De-Qiang Dou ◽  
Ming-Bo Gao
Keyword(s):  
Hydroxyl Radicals ◽  
Cordyceps Militaris ◽  
Mitochondrial Swelling ◽  
Dependent Manner ◽  
Protective Effects ◽  
Fruiting Bodies ◽  
Concentration Dependent Manner ◽  
Mitochondrial Injury

Cordyceps militaris (L.) Link is an entomopathogenic fungus parasitic to Lepidoptera larvae, and is widely used as a folk tonic or invigorant for longevity in China. Although C. militaris has been used in traditional Chinese medicine for millennia, there is still a lack convincing evidence for its anti-aging activities. This study was performed to investigate the effects of polysaccharides from cultivated fruiting bodies of C. militaris (CMP) on mitochondrial injury, antioxidation and anti-aging activity. Fruiting bodies of C. militaris were cultivated artificially under optimized conditions. The spectrophotometric method was used to measure thiobarbituric acid reactive substances (TBARS), mitochondrial swelling, and activities of scavenging superoxide anions in vitro. D-galactose (100 mg/kg/day) was injected subcutaneously into back of the neck of mice for 7 weeks to induce an aging model. The effects of CMP on the activities of catalase (CAT), surperoxide dismutase (SOD), glutathione peroxidase (GPx) and anti-hydroxyl radicals were assayed in vivo using commercial monitoring kits. The results showed that CMP could inhibit mitochondrial injury and swelling induced by Fe2+ -L-Cysteine in a concentration- dependent manner and it also had a significant superoxide anion scavenging effect. Moreover, the activities of CAT, SOD, GPx and anti-hydroxyl radicals in mice liver were increased significantly by CMP. These results indicate that CMP protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial swelling, and increasing the activities of antioxidases. Therefore, CMP may have pharmaceutical values for mitochondrial protection and anti-aging. CMP was the major bioactive component in C. militaris.

scholarly journals Role of pyruvate kinase M2 in oxidized LDL-induced macrophage foam cell formation and inflammation

2020 ◽  
Vol 61 (3) ◽  
pp. 351-364 ◽  
Author(s):  
Amit Kumar ◽  
Priya Gupta ◽  
Minakshi Rana ◽  
Tulika Chandra ◽  
Madhu Dikshit ◽  
...  
Keyword(s):  
Protein Expression ◽  
Pyruvate Kinase ◽  
Foam Cell ◽  
Aerobic Glycolysis ◽  
Oxidized Ldl ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Macrophage Foam Cell ◽  
Pyruvate Kinase M2

Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in oxidized LDL (Ox-LDL)-induced macrophage foam cell formation and inflammation is unknown and therefore was studied. In recombinant mouse granulocyte-macrophage colony-stimulating factor-differentiated murine bone marrow-derived macrophages, early (1–6 h) Ox-LDL treatment induced PKM2 tyrosine 105 phosphorylation and promotes its nuclear localization. PKM2 regulates aerobic glycolysis and inflammation because PKM2 shRNA or Shikonin abrogated Ox-LDL-induced hypoxia-inducible factor-1α target genes lactate dehydrogenase, glucose transporter member 1, interleukin 1β (IL-1β) mRNA expression, lactate, and secretory IL-1β production. PKM2 inhibition significantly increased Ox-LDL-induced ABCA1 and ABCG1 protein expression and NBD-cholesterol efflux to apoA1 and HDL. PKM2 shRNA significantly inhibited Ox-LDL-induced CD36, FASN protein expression, DiI-Ox-LDL binding and uptake, and cellular total cholesterol, free cholesterol, and cholesteryl ester content. Therefore, PKM2 regulates lipid uptake and efflux. DASA-58, a PKM2 activator, downregulated LXR-α, ABCA1, and ABCG1, and augmented FASN and CD36 protein expression. Peritoneal macrophages showed similar results. Ox-LDL induced PKM2- SREBP-1 interaction and FASN expression in a PKM2-dependent manner. Therefore, this study suggests a role for PKM2 in Ox-LDL-induced aerobic glycolysis, inflammation, and macrophage foam cell formation.

scholarly journals Protective Effects of Aqueous Extracts of Flos lonicerae Japonicae against Hydroquinone-Induced Toxicity in Hepatic L02 Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yanfang Gao ◽  
Huanwen Tang ◽  
Liang Xiong ◽  
Lijun Zou ◽  
Wenjuan Dai ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Viability ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Flos Lonicerae ◽  
L02 Cells ◽  
Flos Lonicerae Japonicae

Hydroquinone (HQ) is widely used in food stuffs and is an occupational and environmental pollutant. Although the hepatotoxicity of HQ has been demonstrated both in vitro and in vivo, the prevention of HQ-induced hepatotoxicity has yet to be elucidated. In this study, we focused on the intervention effect of aqueous extracts of Flos lonicerae Japonicae (FLJ) on HQ-induced cytotoxicity. We demonstrated that HQ reduced cell viability in a concentration-dependent manner by administering 160 μmol/L HQ for 12 h as the positive control of cytotoxicity. The aqueous FLJ extracts significantly increased cell viability and decreased LDH release, ALT, and AST in a concentration-dependent manner compared with the corresponding HQ-treated groups in hepatic L02 cells. This result indicated that aqueous FLJ extracts could protect the cytotoxicity induced by HQ. HQ increased intracellular MDA and LPO and decreased the activities of GSH, GSH-Px, and SOD in hepatic L02 cells. In addition, aqueous FLJ extracts significantly suppressed HQ-stimulated oxidative damage. Moreover, HQ promoted DNA double-strand breaks (DSBs) and the level of 8-hydroxy-2′-deoxyguanosine and apoptosis. However, aqueous FLJ extracts reversed HQ-induced DNA damage and apoptosis in a concentration-dependent manner. Overall, our results demonstrated that the toxicity of HQ was mediated by intracellular oxidative stress, which activated DNA damage and apoptosis. The findings also proved that aqueous FLJ extracts exerted protective effects against HQ-induced cytotoxicity in hepatic L02 cells.

Rubus coreanusInhibits Oxidized-LDL Uptake by Macrophages Through Regulation of JNK Activation

2012 ◽  
Vol 40 (05) ◽  
pp. 967-978 ◽  
Author(s):  
Bidur Bhandary ◽  
Geum-Hwa Lee ◽  
Byung-Ok So ◽  
Sun-Young Kim ◽  
Min-Gul Kim ◽  
...  
Keyword(s):  
Foam Cell ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Blood Stasis ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Rubus Coreanus ◽  
Dose Dependent

Oxidized low-density lipoprotein (oxLDL) contributes to atherosclerosis in part by being taken up into macrophages via scavenger receptors and leading to foam cell formation. Herbal compounds that have been used to treat blood stasis (a counterpart of atherosclerosis) for centuries include extracts of medicinal plants in the Rosaceae and Leguminosae families. In this study, we investigated the effect of the unripe Rubus coreanus (Korean black raspberry) fruit extract on oxLDL uptake by murine macrophage cells. In the presence of Rubus coreanus extract (RCE), Dil-labeled oxLDL uptake was inhibited in a dose-dependent manner. SP600125, a specific JNK inhibitor, inhibited the uptake of Dil-oxLDL into macrophages. RCE also inhibited JNK phosphorylation in a time- and dose-dependent manner in macrophages treated with oxLDL. These results indicate that among the mitogen-activated protein kinases, JNK phosphorylation is inhibited by RCE, which is likely the mechanism underlying the RCE-induced inhibition of oxLDL uptake by macrophages.

Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin

2007 ◽  
Vol 292 (4) ◽  
pp. C1323-C1330 ◽  
Author(s):  
Teresia M. Osborn ◽  
Claes Dahlgren ◽  
John H. Hartwig ◽  
Thomas P. Stossel
Keyword(s):  
Platelet Activating Factor ◽  
Protective Role ◽  
Actin Binding ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Blood Concentrations ◽  
Plasma Gelsolin

Gelsolin is a highly conserved intracellular actin-binding protein with an extracellular isoform, plasma gelsolin (pGSN). Blood concentrations of pGSN decrease in response to diverse tissue injuries. Depletion of pGSN to critical levels precedes and often predicts complications of injuries such as lung permeability changes and death. Administration of recombinant pGSN ameliorates such complications and reduces mortality in animal models. One proposed mechanism for pGSN's protective effects is that it inhibits inflammatory mediators generated during primary injuries, since pGSN binds bioactive mediators, including lysophospatidic acid (LPA) and endotoxin in vitro. However, no direct evidence in support of this hypothesis has been available. Here we show that recombinant pGSN modestly inhibited LPA-induced P-selectin upregulation by human platelets in the presence of albumin ( P < 0.0001). However, physiologically relevant pGSN concentrations inhibit platelet-activating factor (PAF)-mediated P-selectin expression by up to 77% ( P < 0.0001). pGSN also markedly inhibited PAF-induced superoxide anion (O2−) production of human peripheral neutrophils (PMN) in a concentration-dependent manner ( P < 0.0001). A phospholipid-binding peptide derived from pGSN (QRLFQVKGRR) also inhibited PAF-mediated O2− generation ( P = 0.024). Therefore, pGSN interferes with PAF- and LPA-induced cellular activation in vitro, suggesting a mechanism for the protective role of pGSN in vivo.

Sign in / Sign up

Export Citation Format

Share Document