Linked Life Data

21276435

Source:http://linkedlifedata.com/resource/pubmed/id/21276435

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2011-5-27
pubmed:abstractText
The role of the aldehyde reductase AKR1A1 in the biosynthesis of gamma-hydroxybutyrate (GHB) has been investigated in cell lines using a specific double stranded siRNA designed to knock down expression of the enzyme. This enzyme, along with the aldo-keto reductase AKR7A2, has been proposed previously to be one of the major succinic semialdehyde reductases in brain. The AKR1A1 siRNA was introduced into the human astrocytoma cell line (1321N1) and AKR1A1 expression was monitored using quantitative reverse-transcriptase PCR and Western blots. Results show an 88% reduction in mRNA levels and a 94% reduction in AKR1A1 protein expression 72 h after transfection with the siRNA. Aldehyde reductase activity was examined in silenced cells by following the aldehyde-dependent conversion of NADPH to NADP at 340 nm. This revealed a 30% decrease in pNBA reductase activity in cell extracts after AKR1A1 silencing. Succinic semialdehyde reductase activity was significantly lower in silenced cells when measured using high concentrations (1mM) of succinic semialdehyde, but not with low concentrations (10 ?M). The effect of silencing on intracellular and extracellular GHB levels was measured using gas chromatography-mass spectrometry. Results show that AKR1A1 has little effect on the production of GHB, indicating that in this cell line alternative enzymes such as the AKR7A2 are likely to play a more significant role in GHB biosynthesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1872-7786
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
191
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
303-7
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The role of aldehyde reductase AKR1A1 in the metabolism of gamma-hydroxybutyrate in 1321N1 human astrocytoma cells.
pubmed:affiliation
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't