Hypothesis on Functional Inadequacy of Thioredoxin and Related Systems in Preeclampsia
- 1 January 1997
- journal article
- research article
- Published by Taylor & Francis in Hypertension in Pregnancy
- Vol. 16 (1) , 35-46
- https://doi.org/10.3109/10641959709069088
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-kB 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.Keywords
This publication has 55 references indexed in Scilit:
- S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular controlNature, 1996
- Thioredoxin-Linked Peroxidase from Human Red Blood Cell: Evidence for the Existence of Thioredoxin and Thioredoxin Reductase in Human Red Blood CellBiochemical and Biophysical Research Communications, 1995
- Underlying disorders associated with severe early-onset preeclampsiaAmerican Journal of Obstetrics and Gynecology, 1995
- Tumour necrosis factorThe Lancet, 1995
- Superoxide dismutase and thioredoxin restore defective p34cdc2 kinase activation in mouse two-cell blockBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1993
- Zellvermittelte Immunität bei schwangerschaftsinduzierten HochdruckerkrankungenGeburtshilfe und Frauenheilkunde, 1992
- Estrogens inhibit copper and cell-mediated modification of low density lipoproteinAtherosclerosis, 1991
- Purified human IκB can rapidly dissociate the complex of the NF-κB transcription factor with its cognate DNACell, 1990
- Novel and potent biological antioxidants on membrane phospholipid peroxidation: 2-hydroxy estrone and 2-hydroxy estradiolBiochemical and Biophysical Research Communications, 1987
- Estrogens as natural antioxidants of membrane phospholipid peroxidationFEBS Letters, 1987