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.
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.
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.
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.
Keywords: Advanced oxidation protein products; Apoptosis; Heme oxygenase-1; Nuclear factor E2-related factor 2; Preeclampsia.
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