beta-Amyloid-specific upregulation of stearoyl coenzyme A desaturase-1 in macrophages.
beta-Amyloid peptide (A beta), a major component of senile plaques, the formation of which is characteristic of Alzheimer's disease (AD), is believed to induce inflammation of the brain mediated by microglia, leading to neuronal cell loss. In this study, we performed an oligonucleotide microarray analysis to investigate the molecular events underlying the A beta-induced activation of macrophages and its specific suppression by the A beta-specific-macrophage-activation inhibitor, RS-1178. Of the approximately 36,000 genes and expressed sequence tags analyzed, eight genes were specifically and significantly upregulated by a treatment with interferon gamma (IFN gamma) and A beta compared to a treatment with IFN gamma alone (p<0.002). We found that the gene for a well-characterized lipogenetic enzyme, stearoyl coenzyme A desaturase-1 (SCD-1), was specifically upregulated by A beta treatment and was suppressed to basal levels by RS-1178. Although the underlying mechanisms remain unknown, our results suggest the presence of a link between AD and SCD-1.
Uryu
Shigeko
S
Lead Discovery Research Laboratories, Sankyo, 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. shigek@shina.sankyo.co.jp
Tokuhiro
Shinya
S
Oda
Tomiichiro
T
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011743:Pyrimidines / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000737:chemistry* / Q000235:genetics*; D013997:Time Factors; D015854:Up-Regulation
D016229:Amyloid beta-Peptides; D011743:Pyrimidines; D012333:RNA, Messenger; C467691:RS 1178; D012313:RNA; D007371:Interferon-gamma; D013230:Stearoyl-CoA Desaturase