Abstract
The Golgi complex plays an important role in cholesterol trafficking in cells, and amyloid beta-peptides (Abetas) 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.
Highlights
The Golgi complex plays an important role in cholesterol trafficking in cells, and amyloid -peptides (As) alter cholesterol trafficking
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
This interaction is reciprocal given that cholesterol modulates expression of amyloid precursor protein and A (10 –13) and cholesterol dynamics such as cholesterol trafficking are affected by A (15, 17–19)
Summary
Vol 278, No 19, Issue of May 9, pp. 17150 –17157, 2003 Printed in U.S.A. Cholesterol Distribution in the Golgi Complex of DITNC1 Astrocytes Is Differentially Altered by Fresh and Aged Amyloid -Peptide-(1– 42)*. It has been reported that apoE levels were increased in astrocytes treated with aged A-(1– 42) (18), and such effects might alter cholesterol distribution in cells. We show that fresh A-(1– 42) has a strikingly different effect on cholesterol levels in the Golgi complex of astrocytes as compared with aged A-(1– 42). Isolation of the astrocyte Golgi complex into different fractions revealed the novel finding that the effects of fresh A-(1– 42) on cholesterol content were opposite on the two Golgi fractions, whereas aged A-(1– 42) had effects similar to those observed with confocal microscopy. PC-PLD activity, cell membrane cholesterol, and apoE levels of astrocytes were associated with effects of fresh A-(1– 42) on cholesterol levels but not with effects of aged A-(1– 42), suggesting different mechanisms for actions of fresh and aged A-(1– 42) on Golgi complex cholesterol. Our data suggest that extracellular A-(1– 42) targets the Golgi complex and disrupts cholesterol homeostasis
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