NDLI: Suppression of statin effectiveness by copper and zinc in yeast and human cells

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Suppression of statin effectiveness by copper and zinc in yeast and human cells

Content Provider	PubMed Central
Author	Fowler, Douglas M. Cooper, Sara J. Stephany, Jason J. Hendon, Natalie Nelson, Sven Fields, Stanley
Abstract	Lovastatin and other statins inhibit HMG-CoA reductase, which carries out an early step in the sterol biosynthesis pathway. Statins lower cholesterol and are widely prescribed to prevent heart disease, but like many drugs, they can interact with nutritionally acquired metabolites. To probe these interactions, we explored the effect of a diverse library of metabolites on statin effectiveness using a Saccharomyces cerevisiae model. In yeast, treatment with lovastatin results in reduced growth. We combined lovastatin with the library of metabolites, and found that copper and zinc ions impaired the ability of the statin to inhibit yeast growth. Using an integrated genomic and metabolomic approach, we found that lovastatin plus metal synergistically upregulated some sterol biosynthesis genes. This altered pattern of gene expression resulted in greater flux through the sterol biosynthesis pathway and an increase in ergosterol levels. Each sterol intermediate level was correlated with expression of the upstream gene. Thus, the ergosterol biosynthetic response induced by statin is enhanced by copper and zinc. In cultured mammalian cells, these metals also rescued statin growth inhibition. Because copper and zinc impair the ability of statin to reduce sterol biosynthesis, dietary intake of these metals could have clinical relevance for statin treatment in humans.
Related Links	http://dx.doi.org/10.1039/c0mb00166j
Ending Page	544
Page Count	12
Starting Page	533
File Format	PDF
ISSN	1742206X
e-ISSN	17422051
Journal	Molecular bioSystems
Issue Number	2
Volume Number	7
Language	English
Publisher Date	2011-01-01
Access Restriction	Open
Subject Keyword	Biotechnology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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