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.

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 Low-density Lipoprotein Improves Motility and Plasma Membrane Integrity of Cryopreserved Canine Epididymal Spermatozoa

2015 ◽  
Vol 29 (5) ◽  
pp. 646-651 ◽  
Author(s):  
N. Prapaiwan ◽  
T. Tharasanit ◽  
S. Punjachaipornpol ◽  
D. Yamtang ◽  
A. Roongsitthichai ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Low Density Lipoprotein ◽  
Membrane Integrity ◽  
Density Lipoprotein ◽  
Low Density ◽  
Plasma Membrane Integrity ◽  
Epididymal Spermatozoa

scholarly journals Adaptor protein 2–mediated endocytosis of the β-secretase BACE1 is dispensable for amyloid precursor protein processing

2012 ◽  
Vol 23 (12) ◽  
pp. 2339-2351 ◽  
Author(s):  
Yogikala Prabhu ◽  
Patricia V. Burgos ◽  
Christina Schindler ◽  
Ginny G. Farías ◽  
Javier G. Magadán ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Amyloid Precursor Protein ◽  
Secretory Pathway ◽  
Brefeldin A ◽  
Adaptor Protein ◽  
Proteolytic Processing ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Processing ◽  
Intermediate Compartment ◽  
Golgi Network

The β-site amyloid precursor protein (APP)–cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease that catalyzes the proteolytic processing of APP and other plasma membrane protein precursors. BACE1 cycles between the trans-Golgi network (TGN), the plasma membrane, and endosomes by virtue of signals contained within its cytosolic C-terminal domain. One of these signals is the DXXLL-motif sequence DISLL, which controls transport between the TGN and endosomes via interaction with GGA proteins. Here we show that the DISLL sequence is embedded within a longer [DE]XXXL[LI]-motif sequence, DDISLL, which mediates internalization from the plasma membrane by interaction with the clathrin-associated, heterotetrameric adaptor protein 2 (AP-2) complex. Mutation of this signal or knockdown of either AP-2 or clathrin decreases endosomal localization and increases plasma membrane localization of BACE1. Remarkably, internalization-defective BACE1 is able to cleave an APP mutant that itself cannot be delivered to endosomes. The drug brefeldin A reversibly prevents BACE1-catalyzed APP cleavage, ruling out that this reaction occurs in the endoplasmic reticulum (ER) or ER–Golgi intermediate compartment. Taken together, these observations support the notion that BACE1 is capable of cleaving APP in late compartments of the secretory pathway.

Effect of aging and obesity on the expression of dyslipidaemia in children from families with familial combined hyperlipidaemia

2006 ◽  
Vol 112 (2) ◽  
pp. 131-139 ◽  
Author(s):  
Ewoud ter Avest ◽  
Allan D. Sniderman ◽  
Sebastian J. H. Bredie ◽  
Albert Wiegman ◽  
Anton F. H. Stalenhoef ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Indirect Evidence ◽  
Low Density ◽  
Tissue Mass ◽  
Adipose Tissue Mass ◽  
And Gender ◽  
Genetically Determined

The aim of the present study was to delineate the mechanism(s) responsible for the increased secretion of VLDL (very-low-density lipoprotein) particles in patients with FCH (familial combined hyperlipidaemia). In 194 young adults (<25 years of age) recruited from families with FCH, we investigated how plasma lipids, (apo)lipoproteins and BMI (body mass index) varied with age. Furthermore, we performed a 5-year follow-up study of clinical and biochemical characteristics of a subset of this population (n=85) stratified by apoB (apolipoprotein B) levels (below or above the 75th percentile adjusted for age and gender). Plasma apoB concentration (r=0.45, P<0.0001), triacylglycerol (triglyceride) concentration (r=0.45, P<0.0001), LDL (low-density lipoprotein) subfraction profile (r=−0.46, P<0.0001) and BMI (r=0.51, P<0.0001) were significantly associated with age. Plasma apoB concentration in the hyperapoB group was already elevated at a young age, whereas other characteristics of FCH, as observed in adults, including triacylglycerol levels >1.5 mmol/l and/or small-dense LDL, were observed only sporadically. After the 5-year follow-up, BMI increased in both groups, and this increase was associated with changes in apoB (r=0.27, P<0.05), triacylglycerol (r=0.30, P<0.01), VLDL cholesterol (r=0.22, P<0.05), VLDL triacylglycerol (r=0.25, P<0.05) and high-density lipoprotein cholesterol (r=−0.27, P<0.05). In conclusion, we have found indirect evidence of a primary, presumably genetically determined, increase in plasma apoB concentration occurring early in life of offspring from families with FCH. However, aging-related post-maturation increases in adipose tissue mass also appear to contribute to an aggravation and/or modulation of this genetically determined apoB overproduction.

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