scholarly journals LRP-1 Commands Two Parallel Signalling Mechanisms to Support Constitutive Tumour Cell Motility in the Absence of Blood Supply

2021 ◽  
Author(s):  
Wei Li ◽  
Cheng Chang ◽  
Xin Tang ◽  
Daniel Mosallaei ◽  
Mei Chen ◽  
...  
Keyword(s):  
Cell Motility ◽  
Blood Supply ◽  
Tumour Cell ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Tumour Cells ◽  
Migration And Invasion ◽  
Autocrine Loop

Tumour cells often face the stress of ischemic (nutrient paucity and hypoxia) environment and must act self-sufficient to migrate toward the nearest blood supply or die. The mechanism that supports the constitutive motility of tumour cells under stress is poorly understood. We and others have previously shown that the low-density lipoprotein receptor-related protein 1 (LRP-1) plays a critical role in tumour cell migration and invasion in vitro and tumour formation in mice. Herein we show that depletion of LRP-1 completely abolishes the self-supported and serum-independent tumour cell motility. More intriguingly, we demonstrate that LRP-1 commands the full tumour cell motility by connecting with two independent cell surface signalling pathways. First, LRP-1 mediates secreted Hsp90α signalling via the Hsp90α > LRP-1 receptor autocrine loop for a half of tumour cell motility. Second, LRP1 stabilizes constitutively activated EGFR signalling that contributes the other half of tumour cell motility. Only combined inhibitions of the secreted Hsp90α autocrine and the EGFR signalling reproduces the effect of LRP1 down-regulation on constitutive tumour cell motility. This study reveals a novel mechanism of how tumour cells migrate in the absence of blood support.

scholarly journals CircLDLR Promotes Papillary Thyroid Carcinoma Tumorigenicity by Regulating miR-637/LMO4 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yuan-ming Jiang ◽  
Wei Liu ◽  
Ling Jiang ◽  
Hongbin Chang
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Induced Apoptosis

Background. Circular RNAs (circRNAs) have been reported to play important roles in the development and progression of papillary thyroid carcinoma (PTC). However, the function and molecular mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the tumorigenesis of PTC remain unknown. Results. In this study, circLDLR was found to be markedly upregulated in PTC tissues and cell lines, and knockdown of circLDLR inhibited PTC cell proliferation, migration, and invasion but induced apoptosis in vitro. Moreover, circLDLR acted as a sponge for miR-637, and miR-637 interference reversed the anticancer effects of circLDLR knockdown on PTC cells. LMO4 was verified to be a target of miR-637; LMO4 upregulation abolished miR-637 mediated inhibition of cell growth and metastasis in PTC. Additionally, circLDLR could indirectly modulate LMO4 via acting as a sponge of miR-637 in PTC cells. Besides that, xenograft analysis showed that circLDLR knockdown suppressed tumor growth in vivo via regulating LMO4 and miR-637. Conclusion. Taken together, these results demonstrated that circLDLR promoted PTC tumorigenesis through miR-637/LMO4 axis, which may provide a novel insight into the understanding of PTC tumorigenesis and be useful in developing potential targets for PTC treatment.

scholarly journals Curcumin Alleviates Palmitic Acid-Induced LOX-1 Upregulation by Suppressing Endoplasmic Reticulum Stress in HUVECs

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ruixi Luo ◽  
Lifeng Zhao ◽  
Shuaishuai Li ◽  
Peng Chen ◽  
La Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Palmitic Acid ◽  
Er Stress ◽  
Umbilical Vein ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Low Density

Excessive free fatty acid- (FFA-) induced endothelial lipotoxicity is involved in the pathogenesis of atherosclerosis. Endoplasmic reticulum (ER) stress is mechanistically related to endothelial lipotoxicity. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major oxidatively modified low-density lipoprotein (OxLDL) receptor in endothelial cells and is highly abundant in atherosclerotic lesions. Curcumin reduces the LOX-1 expression; however, the mechanism underlying this effect remains unknown. In the current study, we explored whether curcumin ameliorates palmitic acid- (PA-) induced endothelial lipotoxicity and LOX-1 upregulation by reducing ER stress in human umbilical vein endothelial cells (HUVECs). We built endothelial lipotoxicity in vitro and found that LOX-1 was upregulated after PA stimulation, during which ER stress played an important role. Next, we observed that curcumin substantially alleviated PA-induced lipotoxicity by restoring cell viability, increasing angiogenesis, and decreasing lipid deposition. Furthermore, LOX-1 upregulation in HUVECs was blocked by curcumin, possibly via ER stress suppression. Overall, our findings demonstrated that curcumin alleviates endothelial lipotoxicity and LOX-1 upregulation, and ER stress inhibition may play a critical role in this effect.

scholarly journals Overexpression of miR-29a-3p Suppresses Proliferation, Migration, and Invasion of Vascular Smooth Muscle Cells in Atherosclerosis via Targeting TNFRSF1A

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Liyi You ◽  
Hao Chen ◽  
Lixin Xu ◽  
Xun Li
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Plaque Formation ◽  
Migration And Invasion ◽  
Low Density

Objective. Increasing evidence highlights the significance of microRNAs (miRNAs) in the progression of atherosclerosis (AS). Our aim was to probe out the role and regulatory mechanism of miR-29a-3p in AS. Methods. An in vivo model of AS was conducted by high-fat diet ApoE-/- mice. Oxidized low-density lipoprotein- (ox-LDL-) exposed vascular smooth muscle cells (VSMCs) were utilized as an in vitro of AS. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected. Hematoxylin and eosin (H&E) and Masson’s staining was presented to investigate the pathological changes. miR-29a-3p and TNFRSF1A expression was detected by RT-qPCR. Proliferative, migrated, and invaded abilities of VSMCs were determined via a series of assays. The interaction between miR-29a-3p and TNFRSF1A was verified through luciferase reporter assay. Results. Upregulated miR-29a-3p and downregulated TNFRSF1A were found both in vitro and in vivo models of AS. miR-29a-3p mimic distinctly decreased the serum levels of TC, TG, and LDL-C and increased serum HDL-C levels. Moreover, its overexpression could ameliorate plaque formation of AS mice. In ox-LDL-induced VSMCs, miR-29a-3p overexpression notably decreased cell proliferation, migration, and invasion, which was reversed by TNFRSF1A overexpression. Also, miR-29a-3p could directly target the 3′UTR of TNFRSF1A. Conclusion. miR-29a-3p overexpression ameliorated plaque formation of AS and suppressed proliferation, migration, and invasion of ox-LDL-induced VSMCs via TNFRSF1A, which offered novel insights into the progression of AS.

Therapeutic Application of Diacylglycerol Oil for Obesity: Serotonin Hypothesis

2012 ◽  
Vol 2 (1) ◽  
pp. 1 ◽  
Author(s):  
Hidekatsu Yanai ◽  
Hiroshi Yoshida ◽  
Yuji Hirowatari ◽  
Norio Tada
Keyword(s):  
Energy Expenditure ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serotonin Release ◽  
Intestinal Cell ◽  
Therapeutic Application ◽  
Postprandial Triglyceride

Characteristics for the serum lipid abnormalities in the obesity/metabolic syndrome are elevated fasting, postprandial triglyceride (TG), and decreased high-density lipoprotein-cholesterol (HDL-C). Diacylglycerol (DAG) oil ingestion has been reported to ameliorate postprandial hyperlipidemia and prevent obesity by increasing energy expenditure, due to the intestinal physiochemical dynamics that differ from triacylglycerol (TAG). Our study demonstrated that DAG suppresses postprandial increase in TG-rich lipoprotein, very low-density lipoprotein (VLDL), and insulin, as compared with TAG in young, healthy individuals. Interestingly, our study also presented that DAG significantly increases plasma serotonin, which is mostly present in the intestine, and mediates thermogenesis, proposing a possible mechanism for a postprandial increase in energy expenditure by DAG. Our other study demonstrated that DAG suppresses postprandial increase in TG, VLDL-C, and remnant-like particle-cholesterol, in comparison with TAG in an apolipoprotein C-II deficient subject, suggesting that DAG suppresses postprandial TG-rich lipoprotein independently of lipoprotein lipase. Further, to understand the molecular mechanisms for DAG-mediated increase in serotonin and energy expenditure, we studied the effects of 1-monoacylglycerol and 2-monoacylglycerol, distinct digestive products of DAG and TAG, respectively, on serotonin release from the Caco-2 cells, the human intestinal cell line. We also studied effects of 1- and 2-monoacylglycerol, and serotonin on the expression of mRNA associated with β-oxidation, fatty acids metabolism, and thermogenesis, in the Caco-2 cells. 1-monoacylglycerol significantly increased serotonin release from the Caco-2 cells, compared with 2-monoacylglycerol by approximately 40%. The expression of mRNA of acyl-CoA oxidase (ACO), fatty acid translocase (FAT), and uncoupling protein-2 (UCP-2), was significantly higher in 1-MOG-treated Caco-2 cells, than 2-MOG-treated cells. The expression of mRNA of ACO, medium-chain acyl-CoA dehydrogenase, FAT, and UCP-2, was significantly elevated in serotonin-treated Caco-2 cells, compared to cells incubated without serotonin. In conclusion, our clinical and in vitro studies suggested a possible therapeutic application of DAG for obesity, and obesity-related metabolic disorders.Key words: Diacylglycerol, intestine, obesity, serotonin, thermogenesis

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

scholarly journals Comparative Evaluation on Impacts of Fibronectin, Heparin–Chitosan, and Albumin Coating of Bacterial Nanocellulose Small-Diameter Vascular Grafts on Endothelialization In Vitro

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1952
Author(s):  
Max Wacker ◽  
Jan Riedel ◽  
Heike Walles ◽  
Maximilian Scherner ◽  
George Awad ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Density Lipoprotein ◽  
Human Albumin ◽  
Water Soluble ◽  
Bacterial Nanocellulose ◽  
Functionally Impaired ◽  
Small Diameter Vascular Grafts

In this study, we contrast the impacts of surface coating bacterial nanocellulose small-diameter vascular grafts (BNC-SDVGs) with human albumin, fibronectin, or heparin–chitosan upon endothelialization with human saphenous vein endothelial cells (VEC) or endothelial progenitor cells (EPC) in vitro. In one scenario, coated grafts were cut into 2D circular patches for static colonization of a defined inner surface area; in another scenario, they were mounted on a customized bioreactor and subsequently perfused for cell seeding. We evaluated the colonization by emerging metabolic activity and the preservation of endothelial functionality by water soluble tetrazolium salts (WST-1), acetylated low-density lipoprotein (AcLDL) uptake assays, and immune fluorescence staining. Uncoated BNC scaffolds served as controls. The fibronectin coating significantly promoted adhesion and growth of VECs and EPCs, while albumin only promoted adhesion of VECs, but here, the cells were functionally impaired as indicated by missing AcLDL uptake. The heparin–chitosan coating led to significantly improved adhesion of EPCs, but not VECs. In summary, both fibronectin and heparin–chitosan coatings could beneficially impact the endothelialization of BNC-SDVGs and might therefore represent promising approaches to help improve the longevity and reduce the thrombogenicity of BNC-SDVGs in the future.

scholarly journals Reductions of copper ion-mediated low-density lipoprotein (LDL) oxidations of trypsin inhibitors, the sweet potato root major proteins, and LDL binding capacities

2020 ◽  
Vol 61 (1) ◽  
Author(s):  
Yeh-Lin Lu ◽  
Chia-Jung Lee ◽  
Shyr-Yi Lin ◽  
Wen-Chi Hou
Keyword(s):  
Sweet Potato ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Trypsin Inhibitors ◽  
Water Soluble ◽  
Affinity Column ◽  
Low Density ◽  
Native Page

Abstract Background The root major proteins of sweet potato trypsin inhibitors (SPTIs) or named sporamin, estimated for 60 to 80% water-soluble proteins, exhibited many biological activities. The human low-density lipoprotein (LDL) showed to form in vivo complex with endogenous oxidized alpha-1-antitrypsin. Little is known concerning the interactions between SPTIs and LDL in vitro. Results The thiobarbituric-acid-reactive-substance (TBARS) assays were used to monitor 0.1 mM Cu2+-mediated low-density lipoprotein (LDL) oxidations during 24-h reactions with or without SPTIs additions. The protein stains in native PAGE gels were used to identify the bindings between native or reduced forms of SPTIs or soybean TIs and LDL, or oxidized LDL (oxLDL). It was found that the SPTIs additions showed to reduce LDL oxidations in the first 6-h and then gradually decreased the capacities of anti-LDL oxidations. The protein stains in native PAGE gels showed more intense LDL bands in the presence of SPTIs, and 0.5-h and 1-h reached the highest one. The SPTIs also bound to the oxLDL, and low pH condition (pH 2.0) might break the interactions revealed by HPLC. The LDL or oxLDL adsorbed onto self-prepared SPTIs-affinity column and some components were eluted by 0.2 M KCl (pH 2.0). The native or reduced SPTIs or soybean TIs showed different binding capacities toward LDL and oxLDL in vitro. Conclusion The SPTIs might be useful in developing functional foods as antioxidant and nutrient supplements, and the physiological roles of SPTIs-LDL and SPTIs-oxLDL complex in vivo will investigate further using animal models.

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