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: M900236-JLR200v1 50/10/2095    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 Google Scholar Articles by Dong, W. Articles by Albers, J. J. PubMed PubMed Citation Articles by Dong, W. Articles by Albers, J. J. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, 2095-2102, October 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Differential effects of simvastatin and pravastatin on expression of Alzheimer’s disease-related genes in human astrocytes and neuronal cells

Weijiang Dong^1,*,, Simona Vuletic^1,* and John J. Albers^2,*

^* Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Department of Medicine, Seattle 98109, WA
Xi’an Jiaotong University School of Medicine, Department of Human Anatomy and Histology and Embryology, Xi’an 710061, People’s Republic of China

² To whom correspondence should be addressed. e-mail: jja{at}u.washington.edu

Inhibitors of HMG-CoA reductase (statins) are widely used medications for reduction of cholesterol levels. Statin use significantly reduces risk of cardiovascular disease but has also been associated with lower risk of other diseases and conditions, including dementia. However, some reports suggest that statins also have detrimental effects on the brain. We provide evidence that simvastatin and pravastatin have significantly different effects on expression of genes related to neurodegeneration in astrocytes and neuroblastoma (SK-N-SH) cells in culture. Simvastatin significantly reduced expression of ABCA1 in astrocytes and neuroblastoma cells (by 79% and 97%, respectively; both P < 0.001). Pravastatin had a similar but attenuated effect on ABCA1 in astrocytes (–54%, P < 0.001) and neuroblastoma cells (–70%, P < 0.001). Simvastatin reduced expression of apolipoprotein E in astrocytes (P < 0.01). Furthermore, both statins reduced expression of microtubule-associated protein tau in astrocytes (P < 0.01), while both statins increased its expression in neuroblastoma cells (P < 0.01). In SK-N-SH cells, simvastatin significantly increased cyclin-dependent kinase 5 and glycogen synthase kinase 3β expression, while pravastatin increased amyloid precursor protein expression. Our data suggest that simvastatin and pravastatin differentially affect expression of genes involved in neurodegeneration and that statin-dependent gene expression regulation is cell type specific.—Dong, W., S. Vuletic, and J. J. Albers. Differential effects of simvastatin and pravastatin on expression of Alzheimer’s disease-related genes in human astrocytes and neuronal cells.

Supplementary key words gene expression • ATP binding cassette transporter A1 • apolipoprotein E • phospholipid transfer protein • microtubule-associated protein tau • amyloid precursor protein

Abbreviations: AD, Alzheimer's disease; apoE/APOE, apolipoprotein E; APP, amyloid precursor protein; BBB, blood-brain barrier; CDK5, cyclin-dependent kinase 5; CSF, cerebrospinal fluid; DAB1, Disabled 1; FPP, farnesyl pyrophosphate; GGPP, geranylgeranyl pyrophosphate; GSK3β, glycogen synthase kinase 3β; MAPT, microtubule-associated protein tau; PLTP, phospholipid transfer protein

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