scholarly journals HDL Inhibited Atherosclerosis Induced by Radiation Injury

2020 ◽  
Author(s):  
Jin Xie ◽  
Ke Zhu ◽  
Qingya Wang ◽  
Pei Zhao ◽  
Lihua Pan ◽  
...  
Keyword(s):  
Western Blotting ◽  
Cell Damage ◽  
Blood Lipid ◽  
Protective Role ◽  
Uvb Radiation ◽  
Phosphatidylinositol 3 Kinase ◽  
Aortic Endothelial Cells ◽  
Akt Phosphorylation ◽  
Atherosclerosis Development ◽  
Apoptosis Process

Abstract Background- HDL inhibits atherosclerosis development from radiation damage; however, the mechanism for this process has not been fully defined. Methods- This study used radiation patients and cultured mouse aortic endothelial cells (MAECs) to investigate the process. Firstly, 158 patients from oncology department of Jingzhou hospital who have got radiation after neck cancers, the arterial function was monitored by B ultrasound, HDL and other blood lipid indexes were tested.Then, MAECs were isolated and cultured, MTT assay was used to test the HDL protective role on UVB radiation, along with this, western blotting was proceed to test some apotosis protein expression and possible molecular.Results- Firstly, those patients with high HDL levels were less likely to develop atherosclerosis, with statistical differences. We observed that MAECs treated with UVB was damaged significantly; HDL reversed the cell damage as dose-depended manner. At mean time, the apoptosis process was assessed and found that HDL inhibited the apoptosis caused by UVB. Western blotting results showed that HDL enhanced phosphatidylinositol 3-kinase (PI3K) and Akt phosphorylation in MAECs.Conclusion- These results suggest that HDL protected UVB-mediated appotosis by activation of a mechanism involving PI3K/Akt signal pathway.

scholarly journals HDL Inhibited Atherosclerosis Induced by Radiation Injury

2020 ◽  
Author(s):  
Jin Xie ◽  
Ke Zhu ◽  
Qingya Wang ◽  
Pei Zhao ◽  
Lihua Pan ◽  
...  
Keyword(s):  
Western Blotting ◽  
Cell Damage ◽  
Blood Lipid ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Uvb Radiation ◽  
Aortic Endothelial Cells ◽  
Akt Phosphorylation ◽  
Apoptosis Protein ◽  
Apoptosis Process

Abstract Background- HDL inhibits atherosclerosis development from radiation damage, nonetheless, the underlying mechanism is yet to be defined.Methods-This study used radiation patients along with cultured mouse aortic endothelial cells (MAECs) to investigate the process. Firstly, 158 patients from the oncology department of Jingzhou hospital who received radiation after neck cancers participated, and their arterial function was monitored by B ultrasound. Similarly, HDL and other blood lipid indexes were also tested. Then, MAECs were isolated and cultured and passed through MTT assay to test the HDL protective role on UVB radiation along with western blotting to test some apoptosis protein expression and possible molecules.Results-Firstly, those patients with high HDL levels were less likely to develop atherosclerosis, with statistical differences. We observed that MAECs treated with UVB were damaged significantly however HDL reversed the cell damage in a dose-depended manner. In the meantime, the apoptosis process was assessed and found that HDL inhibited the apoptosis caused by UVB. Western blotting results showed that HDL enhanced phosphatidylinositol 3-kinase (PI3K) in addition to Akt phosphorylation in MAECs.Conclusion-These results suggest that HDL protected UVB-mediated apoptosis by activation of a mechanism involving PI3K/Akt signaling pathway.

Mechanisms of activation of eNOS by 20-HETE and VEGF in bovine pulmonary artery endothelial cells

2006 ◽  
Vol 291 (3) ◽  
pp. L378-L385 ◽  
Author(s):  
Yuenmu Chen ◽  
Meetha Medhora ◽  
John R. Falck ◽  
Kirkwood A. Pritchard ◽  
Elizabeth R. Jacobs
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Intracellular Signaling ◽  
Pulmonary Arteries ◽  
Phosphatidylinositol 3 Kinase ◽  
Aortic Endothelial Cells ◽  
Akt Phosphorylation ◽  
Molecular Events ◽  
Protein Partners ◽  
Activation Pathways

We have demonstrated that VEGF-induced dilation of bovine pulmonary arteries is associated with activation of cytochrome P-450 family 4 (CYP4) enzymes and eNOS. We hypothesized that VEGF and the CYP4 product 20-HETE would trigger common downstream pathways of intracellular signaling to activate eNOS. We treated bovine pulmonary artery endothelial cells (BPAECs) with 20-HETE (1 μM) or VEGF (8.3 nM) and examined three molecular events known to activate eNOS: 1) phosphorylation at serine 1179, 2) phosphorylation of protein kinase B (Akt), which subsequently phosphorylates eNOS, and 3) association of eNOS with 90-kDa heat shock protein (Hsp90). Both 20-HETE and VEGF increase the phosphorylation of eNOS at serine 1179 and Akt at serine 473. The CYP4 inhibitor dibromododecynyl methyl sulfonamide (DDMS) blocks VEGF-induced phosphorylation of eNOS. VEGF had no effect on the binding of Hsp90 with eNOS, whereas 20-HETE decreased the association of the protein partners. Inhibition of Akt-phosphatidylinositol 3-kinase with wortmannin blocks both 20-HETE and VEGF-induced relaxation of pulmonary arteries, supporting the functional contribution of Akt phosphorylation to the vasoactive actions of both agents. Treatment with radicicol had no effect on 20-HETE-induced relaxation of pulmonary arteries, consistent with an absence of effect on association of Hsp90 to eNOS, whereas radicicol partially blocked VEGF-evoked relaxations, possibly secondary to effects on endpoints other than Hsp90 association with eNOS. In conclusion, VEGF and 20-HETE share eNOS activation pathways, including phosphorylation of serine 1179 and phosphorylation of Akt. Unlike aortic endothelial cells, eNOS activation in BPAECs by either VEGF or 20-HETE does not appear to require increased association of Hsp90.

Nitric Oxide in Life and Death of Neutrophils

2019 ◽  
Vol 26 (31) ◽  
pp. 5764-5780 ◽  
Author(s):  
Svetlana I. Galkina ◽  
Ekaterina A. Golenkina ◽  
Galina M. Viryasova ◽  
Yulia M. Romanova ◽  
Galina F. Sud’ina
Keyword(s):  
Nitric Oxide ◽  
Cell Damage ◽  
Protective Role ◽  
Neutrophil Apoptosis ◽  
High Biological Activity ◽  
Life And Death ◽  
Signalling Molecule ◽  
Activated Neutrophils ◽  
Cell Death Mechanisms ◽  
Prostacyclin Synthase

Background: Nitric Oxide (NO) is a key signalling molecule that has an important role in inflammation. It can be secreted by endothelial cells, neutrophils, and other cells, and once in circulation, NO plays important roles in regulating various neutrophil cellular activities and fate. Objective: To describe neutrophil cellular responses influenced by NO and its concomitant compound peroxynitrite and signalling mechanisms for neutrophil apoptosis. Methods: Literature was reviewed to assess the effects of NO on neutrophils. Results: NO plays an important role in various neutrophil cellular activities and interaction with other cells. The characteristic cellular activities of neutrophils are adhesion and phagocytosis. NO plays a protective role in neutrophil-endothelial interaction by preventing neutrophil adhesion and endothelial cell damage by activated neutrophils. NO suppresses neutrophil phagocytic activity but stimulates longdistance contact interactions through tubulovesicular extensions or cytonemes. Neutrophils are the main source of superoxide, but NO flow results in the formation of peroxynitrite, a compound with high biological activity. Peroxynitrite is involved in the regulation of eicosanoid biosynthesis and inhibits endothelial prostacyclin synthase. NO and peroxynitrite modulate cellular 5-lipoxygenase activity and leukotriene synthesis. Long-term exposure of neutrophils to NO results in the activation of cell death mechanisms and neutrophil apoptosis. Conclusion: Nitric oxide and the NO/superoxide interplay fine-tune mechanisms regulating life and death in neutrophils.

scholarly journals Resveratrol blocks atherosclerosis development by inhibiting IL-1β in macrophages induced by cholesterol

2019 ◽  
Vol 71 (3) ◽  
pp. 551-559
Author(s):  
Yilin Xie ◽  
Zhaoxia Wang ◽  
Haiyun Lin ◽  
Yajun Pan ◽  
Lianyun Wang ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Protective Role ◽  
Expression Level ◽  
Cell Culture Supernatant ◽  
Caveolin 1 ◽  
Cholesterol Treatment ◽  
Atherosclerosis Development ◽  
Umbilical Vein Endothelial Cells ◽  
Antiinflammatory Effects

Resveratrol is a polyphenolic compound that exhibits antiinflammatory and cardioprotective properties. In this study we investigated the protective role of resveratrol on the inflammatory activation of macrophages during pathogenesis of atherosclerosis. Macrophage Ana-1 cells were stimulated by cholesterol and resveratrol, and the cell culture supernatant was collected to treat human umbilical vein endothelial cells (HUVECs). The release of IL-1? into the Ana-1 cell supernatant was quantified by ELISA. Expression of the adhesion molecule ICAM-1 and E-selectin in HUVECs were examined by Western-blotting. Additionally, the adhesion of monocytes in HUVECs under different conditions was tested by cell adhesion analyses. The results indicated that the high cholesterol treatment increased the expression level of IL-1?, while pretreatment with resveratrol inhibited this induction of IL-1? in Ana-1 cells. Resveratrol inhibited the adhesion of monocytes to the endothelium at least partly through inhibition of IL-1? expression in macrophages. Moreover, the expression level of caveolin-1 significantly increased after the pretreatment with resveratrol, indicating that resveratrol enhances reverse cholesterol transport (RCT) in macrophages. Our study indicated that resveratrol has significant antiinflammatory effects and can be considered as a candidate molecule to prevent atherosclerosis.

scholarly journals oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27kip1 signaling: opposite effects of oxLDL and cholesterol loading

2017 ◽  
Vol 313 (3) ◽  
pp. C340-C351 ◽  
Author(s):  
Chongxu Zhang ◽  
Crystal Adamos ◽  
Myung-Jin Oh ◽  
Jugajyoti Baruah ◽  
Manuela A. A. Ayee ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kinase Inhibitor ◽  
Oxidized Ldl ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Akt Inhibitor ◽  
Aortic Endothelial Cells ◽  
Akt Phosphorylation ◽  
Downstream Target ◽  
Underlying Mechanisms

Oxidized modifications of LDL (oxLDL) play a key role in the development of endothelial dysfunction and atherosclerosis. However, the underlying mechanisms of oxLDL-mediated cellular behavior are not completely understood. Here, we compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu2+-oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human aortic endothelial cells (HAECs). Cu2+-oxLDL enhanced HAECs’ proliferation in a dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also enhanced HAEC proliferation. Mechanistically, both Cu2+-oxLDL and LPO-oxLDL enhance HAEC proliferation via activation of Rho, Akt phosphorylation, and a decrease in the expression of cyclin-dependent kinase inhibitor 1B (p27kip1). Both Cu2+-oxLDL or LPO-oxLDL significantly increased Akt phosphorylation, whereas an Akt inhibitor, MK2206, blocked oxLDL-induced increase in HAEC proliferation. Blocking Rho with C3 or its downstream target ROCK with Y27632 significantly inhibited oxLDL-induced Akt phosphorylation and proliferation mediated by both Cu2+- and LPO-oxLDL. Activation of RhoA was blocked by Rho-GDI-1, which also abrogated oxLDL-induced Akt phosphorylation and HAEC proliferation. In contrast, blocking Rac1 in these cells had no effect on oxLDL-induced Akt phosphorylation or cell proliferation. Moreover, oxLDL-induced Rho/Akt signaling downregulated cell cycle inhibitor p27kip1. Preloading these cells with cholesterol, however, prevented oxLDL-induced Akt phosphorylation and HAEC proliferation. These findings provide a new understanding of the effects of oxLDL on endothelial proliferation, which is essential for developing new treatments against neovascularization and progression of atherosclerosis.

scholarly journals Synthetic glycopolymers and natural fucoidans cause human platelet aggregation via PEAR1 and GPIbα

2019 ◽  
Vol 3 (3) ◽  
pp. 275-287 ◽  
Author(s):  
Caroline Kardeby ◽  
Knut Fälker ◽  
Elizabeth J. Haining ◽  
Maarten Criel ◽  
Madelene Lindkvist ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Physiological Role ◽  
Human Platelets ◽  
Minor Role ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Phosphorylation ◽  
Therapeutic Value ◽  
Direct Binding ◽  
A Minor ◽  
Blocking Antibodies

Abstract Fucoidans are sulfated fucose-based polysaccharides that activate platelets and have pro- and anticoagulant effects; thus, they may have therapeutic value. In the present study, we show that 2 synthetic sulfated α-l-fucoside-pendant glycopolymers (with average monomeric units of 13 and 329) and natural fucoidans activate human platelets through a Src- and phosphatidylinositol 3-kinase (PI3K)–dependent and Syk-independent signaling cascade downstream of the platelet endothelial aggregation receptor 1 (PEAR1). Synthetic glycopolymers and natural fucoidan stimulate marked phosphorylation of PEAR1 and Akt, but not Syk. Platelet aggregation and Akt phosphorylation induced by natural fucoidan and synthetic glycopolymers are blocked by a monoclonal antibody to PEAR1. Direct binding of sulfated glycopolymers to epidermal like growth factor (EGF)–like repeat 13 of PEAR1 was shown by avidity-based extracellular protein interaction screen technology. In contrast, synthetic glycopolymers and natural fucoidans activate mouse platelets through a Src- and Syk-dependent pathway regulated by C-type lectin-like receptor 2 (CLEC-2) with only a minor role for PEAR1. Mouse platelets lacking the extracellular domain of GPIbα and human platelets treated with GPIbα-blocking antibodies display a reduced aggregation response to synthetic glycopolymers. We found that synthetic sulfated glycopolymers bind directly to GPIbα, substantiating that GPIbα facilitates the interaction of synthetic glycopolymers with CLEC-2 or PEAR1. Our results establish PEAR1 as the major signaling receptor for natural fucose-based polysaccharides and synthetic glycopolymers in human, but not in mouse, platelets. Sulfated α-l-fucoside-pendant glycopolymers are unique tools for further investigation of the physiological role of PEAR1 in platelets and beyond.

scholarly journals Insights into Arbutin Effects on Bone Cells: Towards the Development of Antioxidant Titanium Implants

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 579 ◽  
Author(s):  
Maria A. Bonifacio ◽  
Giorgia Cerqueni ◽  
Stefania Cometa ◽  
Caterina Licini ◽  
Luigia Sabbatini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Cells ◽  
Cell Damage ◽  
Protective Role ◽  
Titanium Implants ◽  
Point Of View ◽  
Differentiation Markers ◽  
Scavenging Effect ◽  
High Viability

Arbutin is a plant-derived glycosylated hydroquinone with antioxidant features, exploited to combat cell damage induced by oxidative stress. The latter hinders the osseointegration of bone prostheses, leading to implant failure. Little is known about arbutin antioxidant effects on human osteoblasts, therefore, this study explores the in vitro protective role of arbutin on osteoblast-like cells (Saos-2) and periosteum-derived progenitor cells (PDPCs). Interestingly, cells exposed to oxidative stress were protected by arbutin, which preserved cell viability and differentiation. Starting from these encouraging results, an antioxidant coating loaded with arbutin was electrosynthesized on titanium. Therefore, for the first time, a polyacrylate-based system was designed to release the effective concentration of arbutin in situ. The innovative coating was characterized from the physico-chemical and morphological point of view to achieve an optimized system, which was in vitro tested with cells. Morpho-functional evaluations highlighted the high viability and good compatibility of the arbutin-loaded coating, which also promoted the expression of PDPC differentiation markers, even under oxidative stress. These results agreed with the coatings’ in vitro antioxidant activity, which showed a powerful scavenging effect against DPPH radicals. Taken together, the obtained results open intriguing opportunities for the further development of natural bioactive coatings for orthopedic titanium implants.

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