Glioma cell activation by Alzheimer's peptide Abeta1-42, alpha1-antichymotrypsin, and their mixture.
We compared the effects ofAlzheimer's peptide (Abeta1-42), a,-antichymotrypsin (ACT) and an ACT/Abeta1-42 mixture on human glioma DK-MG cells. The solution of Abeta (5 microM) formed by 2-h incubation at room temperature induced tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels by 55 and 45%, respectively, and increased gelatinase B activity by 67%, while exposure of cells to the ACT/Abeta1-42 mixture (1:10 molar ratio ACT: Abeta1-42) under the same experimental conditions showed no effect on IL-6 levels or gelatinase B activity, but strongly induced TNF-alpha (by 190%), compared to the controls. Stimulation of the cells with Abeta1-42 alone, but not with ACT, increased by about 20% low-density lipoprotein (LDL) uptake and mRNA levels for LDL receptor and HMG-CoA reductase, while the ACT/Abeta1-42 mixture significantly increased LDL uptake (by 50%), up-regulated mRNA levels for LDL receptor and HMG-CoA reductase by 48 and 63%, respectively, and increased lipid accumulation by about 20-fold. These data suggest a possible new role for Abeta in Alzheimer's disease through its interaction with the inflammatory reactant, ACT.
Sun
Y X
YX
Department of Medicine, Wallenberg Laboratory, Ing. 46, UMAS, S-20502, Malmö, Sweden.
Wright
H T
HT
Janciauskiene
S
S
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D007700:Kinetics; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000514:alpha 1-Antichymotrypsin / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D017931:DNA Primers; D004273:DNA, Neoplasm; D015850:Interleukin-6; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000514:alpha 1-Antichymotrypsin; C075222:amyloid beta-protein (1-42); D020780:Matrix Metalloproteinase 9; D013936:Thymidine