AOPPs induce HTR-8/SVneo cell apoptosis by downregulating the Nrf-2/ARE/HO-1 anti-oxidative pathway: Potential implications for preeclampsia
AOPPs induce HTR-8/SVneo cell apoptosis by downregulating the Nrf-2/ARE/HO-1 anti-oxidative pathway: Potential implications for preeclampsia
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DOI：
10.1016/j.placenta.2021.06.008
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发表时间：
2021-09-01
期刊：
影响因子：
3.8
通讯作者：
Zhong, Mei
中科院分区：
文献类型：
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作者：
Chen, Shuying;Yin, Qian;Zhong, Mei
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, Nrf2 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.
