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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Glutaredoxins
Pre-Eclampsia
Placenta
Oxidation-Reduction
Cysteine
Endothelial Cells
Messenger RNA
Glutathione
Blood Vessels
Intercellular Signaling Peptides and Proteins
Proteins
Oxidative Stress
Homeostasis
Ischemia
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Staining and Labeling

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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
Murdoch, Colin E. ; Georgiadou, Athina ; Bartkeviciute, Milda ; Broadway-Stringer, Sophie ; Ahmed, Asif. / Glutaredoxin-1 Is up-regulated in preeclampsia and increases soluble Flt-1 expression. In: Reproductive Sciences. 2015 ; Vol. 22, No. Suppl.1. pp. A203-A204.
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title = "Glutaredoxin-1 Is up-regulated in preeclampsia and increases soluble Flt-1 expression",
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.",
author = "Murdoch, {Colin E.} and Athina Georgiadou and Milda Bartkeviciute and Sophie Broadway-Stringer and Asif Ahmed",
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Murdoch, CE, 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, vol. 22, no. Suppl.1, T-302, pp. A203-A204. https://doi.org/10.1177/1933719115579631

Glutaredoxin-1 Is up-regulated in preeclampsia and increases soluble Flt-1 expression. / Murdoch, Colin E.; Georgiadou, Athina; Bartkeviciute, Milda; Broadway-Stringer, Sophie; Ahmed, Asif.

In: Reproductive Sciences, Vol. 22, No. Suppl.1, T-302, 03.2015, p. A203-A204.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Glutaredoxin-1 Is up-regulated in preeclampsia and increases soluble Flt-1 expression

AU - Murdoch, Colin E.

AU - Georgiadou, Athina

AU - Bartkeviciute, Milda

AU - Broadway-Stringer, Sophie

AU - Ahmed, Asif

PY - 2015/3

Y1 - 2015/3

N2 - 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.

AB - 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.

UR - http://journals.sagepub.com/doi/abs/10.1177/1933719115579631

U2 - 10.1177/1933719115579631

DO - 10.1177/1933719115579631

M3 - Meeting abstract

VL - 22

SP - A203-A204

IS - Suppl.1

M1 - T-302

ER -

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