AOPPs induce HTR-8/SVneo cell apoptosis by downregulating the Nrf-2/ARE/HO-1 anti-oxidative pathway: Potential implications for preeclampsia. (1st September 2021)

• Record Type: Journal Article
• Authors: Chen, Shuying; Yin, Qian; Hu, Haoyue; Chen, Qian; Huang, Qitao; Zhong, Mei
• Is Part Of: Placenta. Volume 112(2021)
• Page Start: 1
• Page End: 8
• Publication Date: 2021-09-01
• Subjects: Apoptosis -- Advanced oxidation protein products -- Heme oxygenase-1 -- Nuclear factor E2-related factor 2 -- Preeclampsia; AGEs advanced glycation end-products -- AOPPs advanced oxidation protein products -- Copp cobalt protoporphyrin -- HO-1 heme oxygenase-1 -- NAC N-acetyl-l-cysteine -- Nrf-2 nuclear factor E2-related factor 2 -- PCOS polycystic ovary syndrome -- PE preeclampsia -- ROS reactive oxygen species -- Znpp zinc protoporphyrin; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2021.06.008
• Languages: English
• ISSNs: 0143-4004

Abstract

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. 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. Highlights: AOPPs directly increase the expression of apoptotic proteins. AOPPs significantly inhibit the expression of Nrf-2/ARE/HO-1 in trophoblasts. Knock-down of Nrf-2 aggravated AOPP-induced cell apoptosis in vitro via triggering p53 and caspase activation. AOPPs may induce cell apoptosis via Nrf-2/ARE/HO-1 inhibition. Nrf-2/ARE/HO-1 activation plays a protective role in AOPP-induced cell apoptosis.