Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-11-9
pubmed:abstractText
The present study examined expression of gamma-glutamate-cysteine ligase (GLCL; also known as gamma-glutamylcysteine synthetase), the rate-limiting enzyme for de novo synthesis of glutathione, in the preimplantation mouse embryo. Previous studies indicated that the cleavage stage embryo is unable to synthesize glutathione de novo. It is hypothesized that GLCL mRNA and protein are not normally expressed in the cleavage stage embryo, but either glutathione depletion or oxidation may induce their expression. In untreated embryos, RT-PCR and Western blotting revealed GLCL heavy subunit (GLCL-H) mRNA and protein only at the blastocyst stage of development. Furthermore, while diethyl maleate (DEM) exposure to deplete cellular glutathione did not induce expression of GLCL-H, exposure to tertiary-butyl hydroperoxide (tBH), an oxidizing agent, resulted in significant upregulation of GLCL-H expression in two-cell embryos. Neither treatment affected expression in blastocysts. Finally, HPLC analysis confirmed that tBH-treated embryos experienced oxidative stress, as indicated by an increase in the ratio of oxidized to reduced glutathione. This oxidative stress induced de novo glutathione synthesis in the cleavage stage embryo, as demonstrated by the subsequent recovery of reduced glutathione levels following DEM-induced depletion. In the absence of tBH treatment, however, cleavage stage embryos could not recover GSH after DEM-mediated depletion. This study demonstrates that the preimplantation embryo has the capacity to upregulate glutathione synthesis in response to oxidative stress but not GSH depletion. These results suggest that, while the preimplantation embryo is well adapted to dealing with oxidative stress, it may be poorly protected from GSH-depleting toxicants.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
153-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Regulation of gamma-glutamate-cysteine ligase expression by oxidative stress in the mouse preimplantation embryo.
pubmed:affiliation
Department of Biological Sciences, University of Northern Colorado, Greeley, Colorado, 80639, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.