J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on December 1, 2004 Originally published In Press as doi:10.1194/jlr.M400317-JLR200 on September 17, 2004

Papers In Press, published online ahead of print September 16, 2004
J. Lipid Res., doi:10.1194/jlr.M400317-JLR200
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Submitted on August 19, 2004
Revised on September 3, 2004
Accepted on September 8, 2004

Fatty acids increase presenilin 1 levels and gamma-secretase activity in PSwt-1 cells

Yanzhu Liu, Lin Yang, Karin Conde-Knape, Dirk Beher, Mark Shearman, and Neil S. Shachter

Department of Medicine, Columbia University, New York, NY 10032

Corresponding Author: nss5{at}columbia.edu

Presenilin-1 is an important determinant of the “gamma-secretase” activity necessary for the generation of beta-amyloid, 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 presenilin-1 levels and gamma-secretase activity using stably transfected CHO cells that express human presenilin-1 and the human amyloid precursor protein. Cells cultured with 0.4 mM oleic acid, with 0.1 mM linoleic acid, or with a triglyceride emulsion expressed increased presenilin-1 and beta-amyloid. This effect was independent of any secondary increase in cellular cholesterol. Cells cultured in 0.4 mM oleic acid also exhibited significantly increased gamma-secretase activity. Presenilin-1 mRNA levels were unchanged and pulse-chase experiments indicated that oleic acid slowed presenilin holoprotein degradation. Non-transfected human neuroblastoma cells also showed increased presenilin when cultured in 0.4 mM oleic acid. Lipids may be important biological determinants of presenilin-1 level and gamma-secretase activity.


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[Abstract] [Full Text] [PDF]


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