HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M400317-JLR200v1 M400317-JLR200v2 45/12/2368    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, Y. Articles by Shachter, N. S. Search for Related Content PubMed PubMed Citation Articles by Liu, Y. Articles by Shachter, N. S. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 45, 2368-2376, December 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

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

Yanzhu Liu^*, Lin Yang^*, Karin Conde-Knape^*, Dirk Beher, Mark S. Shearman and Neil S. Shachter^1,*

^* Department of Medicine, Columbia University, New York, NY
Department of Molecular and Cellular Neuroscience, Merck Sharp & Dohme Research Laboratories, Harlow, Essex, United Kingdom

¹ To whom correspondence should be addressed. e-mail: nss5{at}columbia.edu

Presenilin-1 (PS1) is an important determinant of the -secretase activity necessary for the generation of ß-amyloid (Aß), 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 -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 Aß. This effect was independent of any secondary increase in cellular cholesterol. Cells cultured in 0.4 mM OA also exhibited significantly increased -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 -secretase activity.

Abbreviations: Aß, ß-amyloid; AD, Alzheimer's disease; apoE, apolipoprotein E; APP, amyloid precursor protein; CD, cyclodextrin; CMV, cytomegalovirus; ECL, enhanced chemiluminescence; GST, glutathione S-transferase; LA, linoleic acid; MTT, methylthiazoltetrazolium; OA, oleic acid; PS1, presenilin-1; PS1-CTF, C-terminal fragment of cleaved PS1; PS1-NTF, N-terminal fragment of cleaved PS1; SREBP, sterol regulatory element binding protein; TG, triglyceride

Supplementary key words oleic acid • linoleic acid • emulsion • triglycerides • cholesterol • CHO cells • Alzheimer's disease • apolipoprotein E • presenilin • amyloid ß-protein precursor

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. N. Green, H. Martinez-Coria, H. Khashwji, E. B. Hall, K. A. Yurko-Mauro, L. Ellis, and F. M. LaFerla Dietary Docosahexaenoic Acid and Docosapentaenoic Acid Ameliorate Amyloid-{beta} and Tau Pathology via a Mechanism Involving Presenilin 1 Levels J. Neurosci., April 18, 2007; 27(16): 4385 - 4395. [Abstract] [Full Text] [PDF]