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- Title
Nitroxide—HMP—Protects Human Trophoblast HTR-8/SVneo Cells from H 2 O 2 -Induced Oxidative Stress by Reducing the HIF1A Signaling Pathway.
- Authors
Pintye, Diana; Sziva, Réka Eszter; Mastyugin, Maxim; Török, Marianna; Jacas, Sonako; Lo, Agnes; Salahuddin, Saira; Zsengellér, Zsuzsanna K.
- Abstract
Preeclampsia (PE) is a pregnancy-specific syndrome affecting 5–7% of patients. There is no effective treatment available. Early abnormal placental development is associated with oxidative stress (OS) and a release of reactive oxygen species (ROS) in the placenta. This phenomenon leads to downstream signaling, Hypoxia Inducible Factor 1A (HIF1A) stabilization and transcription of the anti-angiogenic factors soluble fms-like tyrosine kinase 1 (sFLT1) and soluble endoglin (sEng), which are known to cause endothelial and trophoblast dysfunction and cardinal features of PE: hypertension, proteinuria and, in severe cases, eclampsia. We tested whether 3-(Hydroxymethyl)-1-oxy-2,2,5,5-tetramethylpyrrolidine (HMP)—a nitroxide-type antioxidant molecule—can reduce placental OS and mitigate PE symptoms in vitro. We induced OS in human trophoblast (HTR-8/SVneo) cells with hydrogen peroxide (H2O2) and assessed whether modulating cell redox function with HMP reduces cell injury, mitochondrial stress and HIF1A and sFLT1 production. Pre-treatment with HMP reduced mitochondrial-derived ROS production, restored LC3B expression and reduced HIF1A and sFLT1 expression in H2O2-exposed HTR-8/SVneo trophoblast cells. HMP improved the mitochondrial electron chain enzyme activity, indicating that a reduction in OS alleviates mitochondrial stress and also reduces anti-angiogenic responses. In reducing placental trophoblast OS, HMP presents a potential novel therapeutic approach for the treatment of PE. Future investigation is warranted regarding the in vivo use of HMP.
- Subjects
TROPHOBLAST; OXIDATIVE stress; CELLULAR signal transduction; NITROXIDES; CELL physiology; PROTEIN-tyrosine kinases; PLACENTAL growth factor
- Publication
Antioxidants, 2023, Vol 12, Issue 8, p1578
- ISSN
2076-3921
- Publication type
Article
- DOI
10.3390/antiox12081578