PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain

被引：89

作者：

Liu, Mali ^{[4
]}

Wu, Guoxin ^{[4
]}

Baysarowich, Jennifer ^{[1
]}

Kavana, Michael ^{[1
]}

Addona, George H. ^{[1
]}

Bierilo, Kathleen K. ^{[1
]}

Mudgett, John S. ^{[2
]}

Pavlovic, Guillaume ^{[3
]}

Sitlani, Ayesha ^{[1
]}

Renger, John J. ^{[4
]}

Hubbard, Brian K. ^{[1
]}

Fisher, Timothy S. ^{[1
]}

Zerbinatti, Celina V. ^{[4
]}

机构：

[1] Merck Res Labs, Atherosclerosis Dept, Rahway, NJ USA

[2] Merck Res Labs, Ctr Genetically Engn Models, Rahway, NJ USA

[3] ICS, Illkirch Graffenstaden, France

[4] Merck Res Labs, Dept Neurol, West Point, PA USA

来源：

JOURNAL OF LIPID RESEARCH | 2010年 / 51卷 / 09期

关键词：

atherosclerosis; low-density lipoprotein; proprotein convertase subtilisin/kexin type 9; beta-site amyloid precursor protein-cleaving enzyme 1; amyloid-beta; Alzheimer's disease; DENSITY-LIPOPROTEIN RECEPTOR; AMYLOID PRECURSOR PROTEIN; AUTOSOMAL-DOMINANT HYPERCHOLESTEROLEMIA; CONVERTASE SUBTILISIN/KEXIN TYPE-9; APOLIPOPROTEIN-E RECEPTOR; FAMILIAL HYPERCHOLESTEROLEMIA; CHOLESTEROL-METABOLISM; SYNAPTIC PLASTICITY; ALZHEIMERS-DISEASE; PLASMA-CHOLESTEROL;

D O I：

10.1194/jlr.M006635

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that regulates hepatic low-density lipoprotein receptor (LDLR) levels in humans. PCSK9 has also been shown to regulate the levels of additional membrane-bound proteins in vitro, including the very low-density lipoprotein receptor (VLDLR), apolipoprotein E receptor 2 (ApoER2) and the beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), which are all highly expressed in the CNS and have been implicated in Alzheimer's disease. To better understand the role of PCSK9 in regulating these additional target proteins in vivo, their steady-state levels were measured in the brain of wild-type, PCSK9-deficient, and human PCSK9 overexpressing transgenic mice. We found that while PCSK9 directly bound to recombinant LDLR, VLDLR, and apoER2 protein in vitro, changes in PCSK9 expression did not alter the level of these receptors in the mouse brain. In addition, we found no evidence that PCSK9 regulates BACE1 levels or APP processing in the mouse brain. In conclusion, our results suggest that while PCSK9 plays an important role in regulating circulating LDL cholesterol levels by reducing the number of hepatic LDLRs, it does not appear to modulate the levels of LDLR and other membrane-bound proteins in the adult mouse brain.-Liu, M., G. Wu, J. Baysarowich, M. Kavana, G. H. Addona, K. K. Bierilo, J. S. Mudgett, G. Pavlovic, A. Sitlani, J. J. Renger, B. K. Hubbard, T. S. Fisher, and C. V. Zerbinatti. PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain. J. Lipid Res. 2010. 51: 2611-2618.

引用

页码：2611 / 2618

页数：8

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