Altered membrane fluidity and lipid raft composition in presenilin-deficient cells

被引：39

作者：

Grimm, M. O. W. ^{[1
]}

Tschaepe, J.-A. ^{[1
]}

Grimm, H. S. ^{[1
]}

Zinser, E. G. ^{[1
]}

Hartmann, T. ^{[1
]}

机构：

[1] Univ Heidelberg, Ctr Mol Biol, D-6900 Heidelberg, Germany

来源：

ACTA NEUROLOGICA SCANDINAVICA | 2006年 / 114卷

关键词：

Alzheimer's disease; presenilin; amyloid beta; cholesterol; gangliosides; lipid rafts; caveolin;

D O I：

10.1111/j.1600-0404.2006.00682.x

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The pathology of Alzheimer's disease is closely connected with lipid metabolism. Processing of amyloid precursor protein (APP) is sensitive to membrane alterations in levels of cholesterol and gangliosides. As cholesterol and gangliosides are major components of rafts and BACE I and gamma-secretase are supposed to be localized to rafts there might be a yet unknown biological function underlying this connection. Increasing evidence shows a close connection between cholesterol homeostasis and APP processing and A beta production respectively. We measured membrane fluidity by anisotropy determination, isolated detergent resistant membrane (DRM) fractions from membrane preparations and determined cholesterol content of these fractions by a coupled enzymatic assay. We found membrane fluidity to be changed in mouse embryonic fibroblasts (MEF) PSI/2 -/- along with altered cholesterol content in DRM fraction of these cells. In addition, total ganglioside levels were enhanced in absence of presenilin (PS).

引用

页码：27 / 32

页数：6

共 61 条

[21] A detergent-insoluble membrane compartment contains Aβ in vivo [J].

Lee, SJ ;

Liyanage, U ;

Bickel, PE ;

Xia, WM ;

Lansbury, PT ;

Kosik, KS .

NATURE MEDICINE, 1998, 4 (06) :730-734

[22] Apolipoprotein E: Far more than a lipid transport protein [J].

Mahley, RW ;

Rall, SC .

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2000, 1 :507-537

[23] Stomatin is a major lipid-raft component of platelet α granules [J].

Mairhofer, M ;

Steiner, M ;

Mosgoeller, W ;

Prohaska, R ;

Salzer, U .

BLOOD, 2002, 100 (03) :897-904

[24] β-secretase processing of the Alzheimer's amyloid protein precursor (APP) [J].

Marlow, L ;

Cain, M ;

Pappolla, MA ;

Sambamurti, K .

JOURNAL OF MOLECULAR NEUROSCIENCE, 2003, 20 (03) :233-239

[25] THE PATHOLOGY OF THE AMYLOID A4 PRECURSOR OF ALZHEIMERS-DISEASE [J].

MASTERS, CL ;

BEYREUTHER, KT .

ANNALS OF MEDICINE, 1989, 21 (02) :89-90

[26] Cholesterol-dependent generation of a seeding amyloid β-protein in cell culture [J].

Mizuno, T ;

Nakata, M ;

Naiki, H ;

Michikawa, M ;

Wang, R ;

Haass, C ;

Yanagisawa, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (21) :15110-15114

[27] DIFFERENTIAL-EFFECTS OF APOLIPOPROTEINS E3 AND E4 ON NEURONAL GROWTH IN-VITRO [J].

NATHAN, BP ;

BELLOSTA, S ;

SANAN, DA ;

WEISGRABER, KH ;

MAHLEY, RW ;

PITAS, RE .

SCIENCE, 1994, 264 (5160) :850-852

[28] Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology [J].

Pappolla, MA ;

Bryant-Thomas, TK ;

Herbert, D ;

Pacheco, J ;

Garcia, MF ;

Manjon, M ;

Girones, X ;

Henry, TL ;

Matsubara, E ;

Zambon, D ;

Wolozin, B ;

Sano, M ;

Cruz-Sanchez, FF ;

Thal, LJ ;

Petanceska, SS ;

Refolo, LM .

NEUROLOGY, 2003, 61 (02) :199-205

[29] Amyloid precursor protein, although partially detergent-insoluble in mouse cerebral cortex, behaves as an atypical lipid raft protein [J].

Parkin, ET ;

Turner, AJ ;

Hooper, NM .

BIOCHEMICAL JOURNAL, 1999, 344 :23-30

[30]

Parkin ET, 1997, J NEUROCHEM, V69, P2179

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