Glutaredoxin-1 Is up-regulated in preeclampsia and increases soluble Flt-1 expression

Colin E. Murdoch, Athina Georgiadou, Milda Bartkeviciute, Sophie Broadway-Stringer, Asif Ahmed

Research output: Contribution to journalMeeting abstract

Abstract

INTRODUCTION: Preeclampsia is a vascular disorder in pregnancyand is biochemical characterization by high soluble Flt-1 and lowplacenta growth factor as well as an imbalance in redox homeostasis.During conditions of high oxidative stress, cysteine residues on keyproteins are reversibly altered by S-glutathionylation, modifying theirfunction. Glutaredoxin-1 (Glrx) enzymatically catalyzes the removal of S-glutathione adducts, conferring reversible signaling dynamics toproteins with redox-sensitive cysteines. The role of Glrx in preeclampsiais unknown.METHODS: Immunohistochemistry and Western blot analysis for Glrx orglutathione were conducted on human placenta samples collected pre-termfrom early onset preeclamptic patients (n=10) or non-preeclamptic induceddeliveries (n=9). Human endothelial cells were infected with adenovirusencoding Glrx or LacZ prior to the cells being exposed to hypoxia (0.1%O2, 24h) to measure changes in soluble Flt-1 (sFlt-1). Quantitative PCRand ELISA were used to measure sFlt-1 at mRNA and protein level.RESULTS: Immunohistochemical staining for GSH revealed lowerS-glutathionylation adducts in preeclampsia placenta in comparison tocontrols. Glrx expression, which catalyses de-glutathionylation wasenhanced in early onset preeclampsia compared to pre-term controlsamples. In contrast, no change was observed in preeclamptic and IUGRplacentas at full term. In endothelial cells overexpressing Glrx, sFlt-1expression was dramatically enhanced at mRNA (3-fold P<0.05) andprotein level (5 fold P>0.01, n=4) after hypoxia andoverexpressing Glrxin mice enhanced levels of circulating sFlt-1 during in vivo ischemia.CONCLUSIONS: Enhanced Glrx expression in preeclamptic placentain line with an apparent decrease in S-glutathionylation may leavekey proteins susceptible to irreversible oxidation in conditions of highoxidative stress.
Original languageEnglish
Article numberT-302
Pages (from-to)A203-A204
Number of pages2
JournalReproductive Sciences
Volume22
Issue numberSuppl.1
DOIs
Publication statusPublished - Mar 2015

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Murdoch, C. E., Georgiadou, A., Bartkeviciute, M., Broadway-Stringer, S., & Ahmed, A. (2015). Glutaredoxin-1 Is up-regulated in preeclampsia and increases soluble Flt-1 expression. Reproductive Sciences, 22(Suppl.1), A203-A204. [T-302]. https://doi.org/10.1177/1933719115579631