期刊
JOURNAL OF LIPID RESEARCH
卷 45, 期 12, 页码 2368-2376出版社
ELSEVIER
DOI: 10.1194/jlr.M400317-JLR200
关键词
oleic acid; linoleic acid; emulsion; triglycerides; cholesterol; CHO cells; Alzheimer's disease; apolipoprotein E; presenilin; amyloid beta-protein precursor
Presenilin-1 (PS1) is an important determinant of the gamma-secretase activity necessary for the generation of P-amyloid (AR), likely the central pathogenic molecule in Alzheimer's disease. Most presenilin is rapidly degraded, and determinants of the level of the active cleaved form are unknown. We examined the influence of fatty acids on PS1 levels and T-secretase activity using stably transfected CHO cells that express human PS1 and the human amyloid precursor protein. Cells cultured with 0.4 mM oleic acid (OA), with 0.1 mM linoleic acid, or with a triglyceride emulsion expressed increased PS1 and Abeta. This effect was independent of any secondary increase in cellular cholesterol. Cells cultured in 0.4 mM OA also exhibited significantly increased gamma-secretase activity. PS1 mRNA levels were unchanged, and pulse-chase experiments indicated that OA slowed presenilin holoprotein degradation. Nontransfected human neuroblastoma cells also showed increased presenilin when cultured in 0.4 mM OA. Lipids may be important biological determinants of PS1 level and gamma-secretase activity.-Liu, Y., L. Yang, K. Conde-Knape, D. Beher, M. S. Shearman, and N. S. Shachter. Fatty acids increase presenilin-1 levels and T-secretase activity in PSwt-1 cells.
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