Regulation of beta-amyloid precursor protein isoform mRNAs by transforming growth factor-beta 1 and interleukin-1 beta in astrocytes.
In cultured astrocytes, all three major transcripts of beta-amyloid precursor protein (APP) were expressed with the ratio for APP695, APP751 and APP770 isoform mRNAs being 1:4:2. In comparison with controls, treatment of astrocytes with transforming growth factor-beta 1 (TGF-beta 1) produced about 6 fold increase in total APP mRNA, while elevation in the interleukin-1 beta (IL-1 beta) treated group was small and may relate to the mitogenic effect of IL-1 beta on astrocytes. Treatment of astrocytes with cytokines also produced marked changes in the upregulation in expression of different APP isoforms. The net increase in mRNAs of KPI-containing isoforms APP751 and APP770 was relatively more than for the APP695 isoform. This phenomenon was mainly related to the differences in the expression of KPI-containing APP isoforms and APP695 isoform in the controls. The present findings provide further evidence for the involvement of astrocytes in a cascade of events leading to the development of senile plaques in Alzheimer's disease and Down's syndrome.
Gray
C W
CW
MRC Collaborative Centre, National Institute for Medical Research, London, UK.
Patel
A J
AJ
D000544:Alzheimer Disease / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D004314:Down Syndrome / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta