Activities per year
Results: Overexpressing Glrx transgenic mice (TG) and littermate controls (WT) underwent timed pregnancy. During pregnancy, TG mice developed hypertension, kidney dysfunction and elevated plasma sFlt-1 compared to WT. Bioinformatics analysis identified several redox-sensitive targets directly relevant to preeclampsia and sFlt-1 regulation. In vitro studies investigated the effects of S-glutathionylation on protein activity in those targets, and consequences on sFlt-1 release. Of significance, S-glutathionylation removal was found to disrupt the spliceosome machinery consequently affecting Flt-1 splicing. Co-immunoprecipitation assays revealed that S-glutathionylation removal disrupted binding between spliceosome partners, promoting sFlt-1 release.
Conclusion: These data support the proposed hypothesis that Glrx’s removal of oxPTMs regulates sFlt-1 expression which may promote the ‘preeclampsia phenotype’ of hypertension and kidney dysfunction. Further studies will need to assess impact of imbalance in redox homeostasis during pregnancy on longterm endothelial and cardiac function. This study highlights how iodo-tandem mass tag proteomics can be used to profile redox sensitive pathways and determine how oxPTMs regulate specific proteins to control angiogenic pathways.
|Number of pages||1|
|Issue number||Suppl 1|
|Publication status||Published - 5 Apr 2020|
|Event||Scottish Cardiovascular Forum: 23rd annual meeting - University of Strathclyde, Glasgow , United Kingdom|
Duration: 1 Feb 2020 → 1 Feb 2020
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- 1 Funding - grants and income which support research related activities
Innovation in modelling Placenta for Maternal and Fetal Health (iPLACENTA) (joint with Mimetas BV, St George's Medical School, University College Cork, Universita Degli Studi di Torino, Institut National de le Sante et de la Recherche Medicale, Universitaet Rostock, Fundacion Para le Investigacion del Hospital Universitario La Fe De La Comunidad Valencia, Aston University, Katholieke Universiteit Leuven, Universiteit Maastricht)
Colin Murdoch (Recipient)1 Mar 2018 → 31 May 2022
Activity: Other activity types › Funding - grants and income which support research related activities