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AOPPs induce HTR-8/SVneo cell apoptosis by downregulating the Nrf-2/ARE/HO-1 anti-oxidative pathway: Potential implications for preeclampsia.
- Source :
-
Placenta [Placenta] 2021 Sep 01; Vol. 112, pp. 1-8. Date of Electronic Publication: 2021 Jun 17. - Publication Year :
- 2021
-
Abstract
- Introduction: Advanced oxidation protein products (AOPPs), which are novel markers of oxidant-mediated protein damage, are prevalent in numerous diseases. We previously demonstrated that AOPPs act as a new class of pathogenic mediators in preeclampsia by causing trophoblast damage and dysfunction. Herein, we explored whether AOPPs could regulate the Nrf-2/ARE/HO-1 anti-oxidative pathway to facilitate the progression of preeclampsia.<br />Methods: To investigate the pathophysiology of preeclampsia, we evaluated the effects of AOPPs on trophoblast damage, apoptotic proteins, and Nrf-2/ARE/HO-1 anti-oxidative pathway expression, as well as their underlying mechanisms.<br />Results: AOPPs directly increased the expression of apoptotic proteins and significantly inhibited the expression of Nrf-2/ARE/HO-1 pathway in trophoblasts. Nrf-2 silencing aggravated the AOPPs-induced cell apoptosis in vitro by activating p53 and caspase cascade, whereas Nrf-2 overexpression had the opposite effect. Moreover, Nrf-2 exerted cytoprotective effects by increasing HO-1.<br />Discussion: These findings suggest that AOPPs induce trophoblast apoptosis by triggering p53 and caspase activation via inhibition of the Nrf-2/ARE/HO-1 anti-oxidative pathway. Hence, Nrf-2/ARE/HO-1 pathway activation plays a protective role in AOPPs-induced cell apoptosis; thus, holding potential as a therapeutic target against preeclampsia.<br />Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antioxidant Response Elements
Apoptosis
Caspases metabolism
Cell Line
Female
Humans
Pre-Eclampsia etiology
Pregnancy
Tumor Suppressor Protein p53 metabolism
Advanced Oxidation Protein Products metabolism
Heme Oxygenase-1 metabolism
NF-E2-Related Factor 2 metabolism
Pre-Eclampsia metabolism
Trophoblasts physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-3102
- Volume :
- 112
- Database :
- MEDLINE
- Journal :
- Placenta
- Publication Type :
- Academic Journal
- Accession number :
- 34237527
- Full Text :
- https://doi.org/10.1016/j.placenta.2021.06.008