Hypothesis on functional inadequacy of thioredoxin and related systems in preeclampsia

Marshall Stark, Lynne Neale, Stuart Woodhead, Bharat Jasani, Karl A. Johansen, Robert W. Shaw

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Objective: To outline a hypothesis suggesting that preeclampsia (preeclamptic toxemia, PET) arises because the thioredoxin-thioredoxin reductase (TRX-TDR) system and related reducing systems inadequately control the abnormal intracellular oxidizing conditions associated with the heightened metabolism of pregnancy. Background: PET has been regarded as a disease of oxidative stress. Thioredoxin is a widely present hormone-responsive antioxidant redox protein participating in diverse biological functions on the basis of sulfydryl-disulfide shuttle activity. Glutaredoxin (GRX) takes part with glutathione in a further similar system which also acts as a hydrogen donor. Hypothesis: The TRX-TDR system is at the crux of those processes which, when not functioning optimally in some pregnancies within the cells of the fetomaternal complex, lead to the phenomena of PET. The consequences are mediated particularly by the altered redox-based modulation of NF-κB activity in promoting TNF transcription. TNF and related cytokines then chronically participate in a vicious prooxidant circle in a widening range of maternal cells to bring about the phenomenon of PET. The earliest hormonal control (by lymphocyte-derived chorionic gonadotrophin) is itself influenced by the immunological interaction of the maternal immune system with paternal antigens and this relationship may explain why PET more commonly affects the first pregnancy. Corollaries: Metabolic inadequacies in the auxiliary systems maintaining the thioredoxin-reducing system (such as provision of NADPH) would increase the probability of abnormal pregnancy. The prooxidant atmosphere and modified sulfhydryl groups within red cells may also diminish the ability of hemoglobin to carry nitric oxide, leading to increased arterial tone and hypertension.

Original languageEnglish
Pages (from-to)35-46
Number of pages12
JournalHypertension in Pregnancy
Volume16
Issue number1
DOIs
Publication statusPublished - 1997

Keywords

  • Estrogens
  • Gonadotrophin
  • Nitric oxide
  • PET
  • Thioredoxin

ASJC Scopus subject areas

  • Internal Medicine
  • Obstetrics and Gynaecology

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