Glioma cell activation by Alzheimer's peptide Abeta1-42, alpha1-antichymotrypsin, and their mixture.

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Abstract

We compared the effects of Alzheimer’s peptide
(Ab1–42), a1-antichymotrypsin (ACT) and an ACT/Ab1–42
mixture on human glioma DK-MG cells. The solution of
Ab (5 mM) formed by 2-h incubation at room temperature
induced tumour necrosis factor-a (TNF-a) and interleukin
(IL)-6 levels by 55 and 45%, respectively, and increased
gelatinase B activity by 67%, while exposure of
cells to the ACT/Ab1–42 mixture (1:10 molar ratio ACT:
Ab1–42) under the same experimental conditions showed
no effect on IL-6 levels or gelatinase B activity, but
strongly induced TNF-a (by 190%), compared to the con-
CMLS, Cell. Mol. Life Sci. 59 (2002) 1734–1743
1420-682X/02/101734-11
© Birkhäuser Verlag, Basel, 2002 CMLS Cellular and Molecular Life Sciences
trols. Stimulation of the cells with Ab1–42 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/Ab1–42 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 Ab in Alzheimer’s disease through its interaction
with the inflammatory reactant, ACT.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology

Keywords

  • Kinetics, Peptide Fragments: chemical synthesis, Human, Interleukin-6: genetics, DNA Primers, DNA, Neoplastic: drug effects, Glioma: physiopathology, Amyloid beta-Protein: pharmacology, Base Sequence, Amyloid beta-Protein: chemical synthesis, Gene Expression Regulation, Neoplasm: biosynthesis, Gelatinase B: metabolism, Peptide Fragments: pharmacology, RNA, Messenger: genetics, Reverse Transcriptase Polymerase Chain Reaction, Support, Non-U.S. Gov't, Thymidine: metabolism, Transcription, Genetic: drug effects, Tumor Cells, Cultured, Tumor Necrosis Factor: genetics, alpha 1-Antichymotrypsin: pharmacology
Original languageEnglish
Pages (from-to)1734-43
JournalCellular and Molecular Life Sciences
Volume59
Issue number10
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes