Low density lipoprotein increases amyloid precursor protein processing to amyloidogenic pathway in differentiated SH-SY5Y cells

Biologia ◽  
2017 ◽  
Vol 72 (2) ◽  
Author(s):  
Panit Yamchuen ◽  
Rattima Jeenapongsa ◽  
Sutisa Nudmamud-Thanoi ◽  
Nanteetip Limpeanchob
Keyword(s):  
Amyloid Precursor Protein ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Neuroblastoma Cells ◽  
Density Lipoprotein ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Processing ◽  
Low Density ◽  
App Processing

AbstractHypercholesterolemia has been considered as a risk factor for Alzheimer’s disease (AD). In addition to low density lipoprotein (LDL), oxidized LDL plays some roles in AD pathology. Neurodegenerative effect of oxidized LDL was supported by the increased oxidative stress in neurons. To further investigate the role of oxidized LDL, the present study aimed to test its effect on amyloid precursor protein (APP) processing. The release of soluble APP (sAPP) was evaluated in differentiated SH-SY5Y neuroblastoma cells exposed to native (non-oxidized) or oxidized human LDL including mildly and fully oxidized LDL (mox- and fox-LDL). Non-amyloidogenic and amyloidogenic pathways were investigated using specific antibody against sAPP

scholarly journals Polar phospholipids from bovine endogenously oxidized low density lipoprotein interfere with follicular thecal function

2005 ◽  
Vol 35 (3) ◽  
pp. 531-545 ◽  
Author(s):  
B Löhrke ◽  
T Viergutz ◽  
B Krüger
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Steroidogenic Enzymes ◽  
Cox 2

The role of endogenously oxidized low density lipoprotein (oxLDL) in follicular steroidogenic regulation is unknown. Information may be important in order to elucidate ovulatory dysregulation in disordered lipid metabolism. To obtain specific data, we studied the effect of polar phospholipids (PL) isolated from oxLDL with different endogenous levels of lipohydroperoxides (LHP) on the thecal expression of mRNA encoding steroidogenic enzymes and cyclooxygenase 2 (COX-2), and on the thecal production of superoxide and progesterone. Large (preovulatory) bovine follicles were used and analyses of thecal fragments from single follicles were performed by radioimmunoassays, chemiluminescence assays and quantitative RT-PCR. Basal concentration of mRNA for several lipoprotein receptors exceeded by about 10-times the basal level of mRNA encoding steroidogenic enzymes, suggesting that preovulatory theca receptors may favour uptake of oxLDL. PL (5–11 pmol phosphorus/ml) decreased (up to 0.5-times the control) progesterone synthesis, production of superoxide and levels of P450 cholesterol side chain cleavage (P450 scc), 3β-hydroxysteroid dehydrogenase and COX-2 mRNA. Abundance of COX-2 transcripts in thecal tissue incubated with forskolin depended on the progesterone/17β-oestradiol ratio of the follicle fluid, i.e. the previous microenvironment in vivo. PL effects were mimicked by the platelet-activating factor (PAF). WEB 2086, a PAF receptor blocker, did not always abolish these responses, suggesting that the effects were not mediated solely by this receptor. PAF interfered dose-dependently with LH-induced responses, indicating interference with LH signalling. PL from mildly oxidized LDL (0.5 nmol/ml LHP) tended to exert greater effects than PL from oxLDL containing 1.5 nmol/ml LHP. In consideration of the known physiologic role of progesterone, COX-2 and possibly superoxide, these results provide evidence for a potential of PL from oxLDL to induce ovulatory dysregulation and suggest that the extent of the LDL oxidation seems to be important for interfering with thecal responses to the preovulatory LH surge.

scholarly journals LDL-lipids from patients with hypercholesterolaemia and Alzheimer's disease are inflammatory to microvascular endothelial cells: mitigation by statin intervention

2015 ◽  
Vol 129 (12) ◽  
pp. 1195-1206 ◽  
Author(s):  
H.K. Irundika Dias ◽  
Caroline L.R. Brown ◽  
M. Cristina Polidori ◽  
Gregory Y.H. Lip ◽  
Helen R. Griffiths
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Microvascular Endothelial Cells ◽  
Low Density ◽  
High Cholesterol ◽  
Inflammatory Damage

We have established a novel anti-inflammatory and antioxidant role of statins towards oxidized fats in the “bad” cholesterol low density lipoprotein (LDL) particle from the blood of mid-life adults with high cholesterol. Oxidized LDL-fat levels were also higher in the blood of patients with dementia and caused inflammatory damage to cells that line blood vessels.

scholarly journals Role of LOX-1 (Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1) as a Cardiovascular Risk Predictor

2020 ◽  
Author(s):  
Joaquim Barreto ◽  
Sotirios K. Karathanasis ◽  
Alan Remaley ◽  
Andrei C. Sposito
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Risk ◽  
Neutralizing Antibodies ◽  
Randomized Clinical Trials ◽  
Transmembrane Protein ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density

Atherosclerosis, the underlying cause of cardiovascular disease (CVD), is a worldwide cause of morbidity and mortality. Reducing ApoB-containing lipoproteins—chiefly, LDL (low-density lipoprotein)—has been the main strategy for reducing CVD risk. Although supported by large randomized clinical trials, the persistence of residual cardiovascular risk after effective LDL reduction has sparked an intense search for other novel CVD biomarkers and therapeutic targets. Recently, Lox-1 (lectin-type oxidized LDL receptor 1), an innate immune scavenger receptor, has emerged as a promising target for early diagnosis and CV risk prediction and is also being considered as a treatment target. Lox-1 was first described as a 50 kDa transmembrane protein in endothelial cells responsible for oxLDL (oxidized LDL) recognition, triggering downstream pathways that intensify atherosclerosis via endothelial dysfunction, oxLDL uptake, and apoptosis. Lox-1 is also expressed in platelets, where it enhances platelet activation, adhesion to endothelial cells, and ADP-mediated aggregation, thereby favoring thrombus formation. Lox-1 was also identified in cardiomyocytes, where it was implicated in the development of cardiac fibrosis and myocyte apoptosis, the main determinants of cardiac recovery following an ischemic insult. Together, these findings have revealed that Lox-1 is implicated in all the main steps of atherosclerosis and has encouraged the development of immunoassays for measurement of sLox-1 (serum levels of soluble Lox-1) to be used as a potential CVD biomarker. Finally, the recent development of synthetic Lox-1 inhibitors and neutralizing antibodies with promising results in animal models has made Lox-1 a target for drug development. In this review, we discuss the main findings regarding the role of Lox-1 in the development, diagnosis, and therapeutic strategies for CVD prevention and treatment.

scholarly journals Secretases Related to Amyloid Precursor Protein Processing

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 983
Author(s):  
Xiaoling Liu ◽  
Yan Liu ◽  
Shangrong Ji
Keyword(s):  
Amyloid Precursor Protein ◽  
Drug Targets ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Processing ◽  
Pathological Feature ◽  
App Processing ◽  
New Directions ◽  
Processing Pathways ◽  
Potential Drug Targets

Alzheimer’s disease (AD) is a common neurodegenerative disease whose prevalence increases with age. An increasing number of findings suggest that abnormalities in the metabolism of amyloid precursor protein (APP), a single transmembrane aspartic protein that is cleaved by β- and γ-secretases to produce β-amyloid protein (Aβ), are a major pathological feature of AD. In recent years, a large number of studies have been conducted on the APP processing pathways and the role of secretion. This paper provides a summary of the involvement of secretases in the processing of APP and the potential drug targets that could provide new directions for AD therapy.

scholarly journals Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content

1997 ◽  
Vol 322 (3) ◽  
pp. 893-896 ◽  
Author(s):  
Marco RACCHI ◽  
Roberta BAETTA ◽  
Nathalie SALVIETTI ◽  
Paola IANNA ◽  
Guido FRANCESCHINI ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Amyloid Precursor Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Indirect Evidence ◽  
Proteolytic Processing ◽  
Precursor Protein ◽  
Low Density ◽  
Membrane Composition ◽  
Simultaneous Treatment

Plasma-membrane composition plays a crucial role in most of the cellular functions that depend on membrane processes. In virtually all cell types the proteolytic processing of Alzheimer amyloid precursor protein (APP) to generate soluble APP (sAPP) is believed to occur at the plasma membrane or in its immediate proximity. Alteration of this metabolic pathway has been linked to the pathogenesis of Alzheimer's disease. We analysed the effect of membrane cholesterol enrichment on APP metabolism. Incubation of COS cells with increasing concentrations of non-esterified cholesterol carried by rabbit β-very low-density lipoprotein caused a dose-dependent inhibition of sAPP release: 70% inhibition with 10 μg/ml non-esterified cholesterol. A less pronounced inhibitory effect was observed on treatment with human low-density lipoprotein. Inhibition of sAPP release was independent of receptor-mediated lipoprotein metabolism since simultaneous treatment with chloroquine did not modify the effect of lipoprotein treatment. In addition, treatment with cholesterol dissolved in either ethanol or methyl-β-cyclodextrin elicited the same effect. Excess non-esterified cholesterol did not cause cell toxicity. Cell cholesterol mass inversely correlated with sAPP release. Progesterone, which inhibits shuttling of non-esterified cholesterol between the plasma membrane and intracellular pools, had no effect on the inhibition of sAPP release from cholesterol-loaded cells, providing indirect evidence that cholesterol may act at the plasma membrane.

Modified and Dysfunctional Lipoproteins in Atherosclerosis: Effectors or Biomarkers?

2019 ◽  
Vol 26 (9) ◽  
pp. 1512-1524 ◽  
Author(s):  
Alexander N. Orekhov ◽  
Igor A. Sobenin
Keyword(s):  
Health Care ◽  
High Density Lipoprotein ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Fundamental Question ◽  
Low Density ◽  
Industrialized Countries ◽  
New Methods

Atherosclerotic diseases are the leading cause of mortality in industrialized countries. Correspondingly, studying the pathogenesis of atherosclerosis and developing new methods for its diagnostic and treatment remain in the focus of current medicine and health care. This review aims to discuss the mechanistic role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in atherogenesis. In particular, the generally accepted hypothesis about the key role of oxidized LDL in atherogenesis is questioned, and an alternative concept of multiple modification of LDL is presented. The fundamental question discussed in this review is whether LDL and HDL are effectors or biomarkers, or both. This is important for understanding whether lipoproteins are a therapeutic target or just diagnostic indicators.

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