Format

Send to

Choose Destination
PLoS Genet. 2005 Dec;1(6):e77. Epub 2005 Dec 16.

The flavoring agent dihydrocoumarin reverses epigenetic silencing and inhibits sirtuin deacetylases.

Author information

1
School of Public Health, University of California Berkeley, Berkeley, California, USA. drewski@berkeley.edu

Abstract

Sirtuins are a family of phylogenetically conserved nicotinamide adenine dinucleotide-dependent deacetylases that have a firmly established role in aging. Using a simple Saccharomyces cerevisiae yeast heterochromatic derepression assay, we tested a number of environmental chemicals to address the possibility that humans are exposed to sirtuin inhibitors. Here we show that dihydrocoumarin (DHC), a compound found in Melilotus officinalis (sweet clover) that is commonly added to food and cosmetics, disrupted heterochromatic silencing and inhibited yeast Sir2p as well as human SIRT1 deacetylase activity. DHC exposure in the human TK6 lymphoblastoid cell line also caused concentration-dependent increases in p53 acetylation and cytotoxicity. Flow cytometric analysis to detect annexin V binding to phosphatidylserine demonstrated that DHC increased apoptosis more than 3-fold over controls. Thus, DHC inhibits both yeast Sir2p and human SIRT1 deacetylases and increases p53 acetylation and apoptosis, a phenotype associated with senescence and aging. These findings demonstrate that humans are potentially exposed to epigenetic toxicants that inhibit sirtuin deacetylases.

PMID:
16362078
PMCID:
PMC1315280
DOI:
10.1371/journal.pgen.0010077
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests. The authors have declared that no competing interests exist.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center