Linked Life Data

7493965

Source:http://linkedlifedata.com/resource/pubmed/id/7493965

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
1996-1-11
pubmed:abstractText
To better understand the regulation of gene expression by amino acids, we studied the effects of these macronutrients on fatty acid synthase (FAS), an enzyme crucial for energy storage. When HepG2 cells were fed serum-free media selectively deficient in each amino acid, the omission of any single classic essential amino acid as well as Arg or His (essential in some rapidly growing cells) resulted in FAS mRNA levels that were about half of those in complete medium. Control message levels were unaffected and omission of nonessential amino acids did not alter FAS expression. FAS mRNA levels peaked 12-16 h after feeding complete and Ser (nonessential)-deficient media but did not increase in cells fed Lys (essential)-deficient medium. With Lys, FAS mRNA increased over the physiologic concentration range of 15-150 microM, and low concentrations of lysine decreased FAS but not apoB protein mass. Transcription inhibitors mimicked treatment with Lys-deficient media, and nuclear run-off assays showed that Lys-deficient media abolished FAS but not apoB transcription. After treatment with Lys-deficient media, the intracellular Lys pool was rapidly depleted in association with an increase of uncharged (deacylated) tRNA Lys from < 1 to 64% of available tRNA Lys. Even in the presence of the essential amino acid His, increasing the level of uncharged tRNA His with histidinol, a competitive inhibitor of the histidinyl-tRNA synthetase, blocked FAS expression. Tyrosinol treatment did not alter FAS mRNA levels. These results suggest that essential amino acids regulate FAS expression by altering uncharged tRNA levels, a novel mechanism for nutrient control of gene expression in mammalian cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29323-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Essential amino acids regulate fatty acid synthase expression through an uncharged transfer RNA-dependent mechanism.
pubmed:affiliation
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't