Cholesterol distribution in the Golgi complex of DITNC1 astrocytes is differentially altered by fresh and aged amyloid beta-peptide-(1-42)

• Published in: The Journal of biological chemistry 2003-05, Vol.278 (19), p.17150-17157
• Main Authors: Igbavboa, Urule, Pidcock, Justine M, Johnson, Leslie N A, Malo, Todd M, Studniski, Ann E, Yu, Su, Sun, Grace Y, Wood, W Gibson
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - pharmacology; Animals; Astrocytes - metabolism; Astrocytes - ultrastructure; Biological Transport - drug effects; Cells, Cultured; Cholesterol - metabolism; Golgi Apparatus - metabolism; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Rats
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M301150200

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.