Disulfiram inhibits placental soluble FMS-like tyrosine kinase-1 and soluble endoglin secretion independent of the proteasome

R Hastie; L Ye; NJ Hannan; FC Brownfoot; P Cannon; V Nguyen; S Tong; TJ Kaitu'u-Lino

Journal article

Disulfiram inhibits placental soluble FMS-like tyrosine kinase-1 and soluble endoglin secretion independent of the proteasome

R Hastie, L Ye, NJ Hannan, FC Brownfoot, P Cannon, V Nguyen, S Tong, TJ Kaitu'u-Lino

Pregnancy Hypertension | ELSEVIER SCI LTD | Published : 2018

DOI: 10.1016/j.preghy.2018.09.005

Abstract

Preeclampsia is associated with intermittent placental hypoxia, inflammation and the release of antiangiogenic factors, namely sFLT-1 and sEng. These factors cause maternal endothelial dysfunction and the manifestation of clinical disease. Disulfiram is a dehydrogenase inhibitor used to treat alcoholism and has been suggested as a proteasome inhibitor. Inhibiting the proteasome has been previously shown to reduce FLT-1 gene expression. Thus, we aim to investigate whether disulfiram alters the secretion of sFLT-1 and sEng and reduces endothelial dysfunction. Methods and results: We assessed the effects of disulfiram on primary cytotrophoblast and human umbilical vein endothelial cells (HUVECs..

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University of Melbourne Researchers

Roxanne Hastie Author

Louie Ye Author

Natalie Hannan Author

Fiona Brownfoot Author

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Grants

Funding Acknowledgements

S Tong (#1136418), T.J. Kaitu'u-Lino (#1062418), N.J. Hannan (#1146128) and F. Brownfoot (#1142636) were supported by NHMRC Fellowships. The funders had no role in study design, data collection, analysis, decision to publish or the preparation of the manuscript.