Doridot 2014 Antioxid Redox Signal
|Doridot LD Chatre LD, Ducat A, Vilotte JL, Lombes A, Méhats C, Barbaux S, Calicchio R, Ricchetti M, Vaiman D (2014) Nitroso-redox balance and mitochondrial homeostasis are regulated by STOX1, a pre-eclampsia associated gene. Antioxid Redox Signal 21:819-34.|
Abstract: Aims: Storkhead Box 1 (STOX1) is a winged-helix transcription factor implicated in the genetic forms of a high-prevalence human gestational disease, preeclampsia. STOX1 overexpression confers preeclampsia-like transcriptomic features to trophoblastic cell lines, and preeclampsia symptoms to pregnant mice. The aim of this work was to evaluate the impact of STOX1 on free radical equilibrium and mitochondrial function, in vitro and in vivo. Results: Transcriptome analysis of STOX1-transgenic versus non-transgenic placentas at 16.5 days of gestation revealed alterations of mitochondria-related pathways. Placentas overexpressing STOX1 displayed altered mitochondrial mass and were severely biased towards protein nitration, indicating nitroso-redox imbalance in vivo. Trophoblast cells overexpressing STOX1 displayed an increased mitochondrial activity at 20% O2 and in hypoxia, despite a reduction of the mitochondrial mass in this situation. STOX1 overexpression is therefore associated to hyperactive mitochondria leading to increased free radical production. Moreover, nitric oxide (NO) production pathways were activated, resulting in peroxynitrite formation. At low oxygen pressure, STOX1 overexpression in the placenta as well as in a trophoblast cell line, switched the free radical balance from Reactive Oxygen Species (ROS) to Reactive Nitrogen Species (RNS). Innovation: In preeclamptic placentas, NO interacts with ROS to generate peroxynitrite and nitrated proteins as end products. This process will deprive the maternal organism of NO, a crucial vasodilator molecule. Conclusion: Our data posit STOX1 as a genetic switch in the ROS/RNS balance and suggest an explanation for elevated blood pressure in preeclampsia.
• Keywords: JEG-3 cells
Labels: MiParea: Respiration
Organism: Human Tissue;cell: Endothelial;epithelial;mesothelial cell, Other cell lines
Coupling state: LEAK, ROUTINE, ET Pathway: ROX HRR: Oxygraph-2k