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

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