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J. Biol. Chem., Vol. 278, Issue 19, 17150-17157, May 9, 2003
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From the The Golgi complex plays an important role in
cholesterol trafficking in cells, and amyloid
Cholesterol Distribution in the Golgi Complex of
DITNC1 Astrocytes Is Differentially Altered by Fresh and Aged
Amyloid
-Peptide-(1-42)*
,
,
,
,
,
¶
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
-peptides
(A
s) alter cholesterol trafficking. The hypothesis was tested that
fresh and aged A
-(1-42) would differentially modify Golgi
cholesterol content in DINTC1 astrocytes and that the effects of
A
-(1-42) would be associated with the region of the Golgi
complex. Two different methods were used to determine the effects of
A
-(1-42) on Golgi complex cholesterol. Confocal microscopy showed
that fresh A
-(1-42) significantly increased cholesterol and that
aged A
-(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 A
-(1-42)
similar to those observed with confocal microscopy but revealed the
novel finding that fresh A
-(1-42) had opposite effects on the two
Golgi fractions suggesting a specificity of A
-(1-42) perturbation
of the Golgi complex. Phosphatidylcholine-phospholipase D
activity, cell membrane cholesterol, and apolipoprotein E levels were
associated with effects of fresh A
-(1-42) on cholesterol
distribution but not with effects of aged A
-(1-42), arguing against
a common mechanism. Extracellular A
-(1-42) targets the Golgi
complex and disrupts cell cholesterol homeostasis, and this action of
A
-(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.
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