Effects of Alzheimer's peptide and alpha1-antichymotrypsin on astrocyte gene expression.
We employed gene array technology to investigate the effects of alpha1-antichymotrypsin (ACT), soluble or fibrillar Alzheimer's peptide (Abeta(1-42)) alone and the combination of ACT/Abeta(1-42) on human astrocytes. Using a 1.2-fold change as significance threshold, 398 astrocyte genes showed altered expression in response to these treatments compared to controls. Of the 276 genes affected by the ACT/soluble Abeta(1-42) combination, 195 (70.6%) were suppressed. The ACT/fibrillar Abeta(1-42) combination affected expression of 64 genes of which 58 (90.5%) were up-regulated. The most prominent gene expression changes in response to the ACT/soluble Abeta(1-42), were the down-regulation of at least 60 genes involved in transcription, signal transduction, apoptosis and neurogenesis. The ACT/fibril Abeta(1-42) increased the expression of genes involved in transcription regulation and signal transduction. Surprisingly, gene expression of astrocytes exposed to soluble or fibrillar Abeta(1-42) alone was largely unaffected. Thus, the molecular forms generated by the combination of ACT/Abeta(1-42) alter expression of astrocyte genes more profoundly in breadth and magnitude than soluble or fibrillar Abeta(1-42) alone, suggesting that pathogenic effects of Abeta(1-42) may occur as a consequence of its association with other proteins.
Baker
Crystal
C
Institute of Genetics, School of Molecular Medical Sciences, University of Nottingham, Nottingham NG7 2UH, UK. mrxcab1@nottingham.ac.uk
Nielsen
Henrietta M
HM
Minthon
Lennart
L
Wright
H T
HT
Chappell
Sally
S
Okyere
John
J
May
Sean
S
Morgan
Kevin
K
Kalsheker
Noor
N
Janciauskiene
Sabina M
SM
D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D010446:Peptide Fragments / Q000008:administration & dosage*; D020543:Proteome / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D020543:Proteome; D000514:alpha 1-Antichymotrypsin; C075222:amyloid beta-protein (1-42)