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Originally published In Press as doi:10.1074/jbc.M301150200 on February 12, 2003

J. Biol. Chem., Vol. 278, Issue 19, 17150-17157, May 9, 2003
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Cholesterol Distribution in the Golgi Complex of DITNC1 Astrocytes Is Differentially Altered by Fresh and Aged Amyloid beta -Peptide-(1-42)*

Urule IgbavboaDagger , Justine M. PidcockDagger , Leslie N. A. JohnsonDagger , Todd M. MaloDagger , Ann E. StudniskiDagger , Su Yu§, Grace Y. Sun§, and W. Gibson WoodDagger

From the Dagger  Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center and the Department of Pharmacology, University of Minnesota School of Medicine, Minneapolis, Minnesota 55417 and the § Department of Biochemistry, University of Missouri, Columbia, Missouri 65211

The Golgi complex plays an important role in cholesterol trafficking in cells, and amyloid beta -peptides (Abeta s) alter cholesterol trafficking. The hypothesis was tested that fresh and aged Abeta -(1-42) would differentially modify Golgi cholesterol content in DINTC1 astrocytes and that the effects of Abeta -(1-42) would be associated with the region of the Golgi complex. Two different methods were used to determine the effects of Abeta -(1-42) on Golgi complex cholesterol. Confocal microscopy showed that fresh Abeta -(1-42) significantly increased cholesterol and that aged Abeta -(1-42) significantly reduced cholesterol content in the Golgi complex. Isolation of the Golgi complex into two fractions using density gradient centrifugation showed effects of aged Abeta -(1-42) similar to those observed with confocal microscopy but revealed the novel finding that fresh Abeta -(1-42) had opposite effects on the two Golgi fractions suggesting a specificity of Abeta -(1-42) perturbation of the Golgi complex. Phosphatidylcholine-phospholipase D activity, cell membrane cholesterol, and apolipoprotein E levels were associated with effects of fresh Abeta -(1-42) on cholesterol distribution but not with effects of aged Abeta -(1-42), arguing against a common mechanism. Extracellular Abeta -(1-42) targets the Golgi complex and disrupts cell cholesterol homeostasis, and this action of Abeta -(1-42) could alter cell functions requiring optimal levels of cholesterol.


* This work was supported by National Institutes of Health Grants AA-10806 and 1P0AG-18357, United States Army Medical Research and Material Command Grant DAMD 17-00-1-0583, and the Department of Veterans Affairs.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Veterans Affairs Medical Center, GRECC, 11G, One Veterans Dr., Minneapolis, MN 55417. Tel.: 612-467-3303; Fax: 612-725-2084; E-mail: Woodx002@umn.edu.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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