Environmental BPDE induced human trophoblast cell apoptosis by up-regulating lnc-HZ01/p53 positive feedback loop.

Autor: Huang X; Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China., Ma C; Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China., Huang W; Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China., Dai M; Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China., Yang J; Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China., Xu X; Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China., Deng Y; Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China., Yang Y; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China., Zhang H; Department of Toxicology, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China. Electronic address: zhanghd29@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2022 Jun 01; Vol. 237, pp. 113564. Date of Electronic Publication: 2022 Apr 25.
DOI: 10.1016/j.ecoenv.2022.113564
Abstrakt: Human trophoblast cell apoptosis may induce miscarriage. Trophoblast cells are sensitive to environmental BaP-7,8-dihydrodiol-9,10-epoxide (BPDE). However, how BPDE induces human trophoblast cell apoptosis is still largely elusive. In this work, we used BPDE-treated human trophoblast cells and villous tissues collected from recurrent miscarriage and health control groups to explore the underlying mechanism of BPDE-induced human trophoblast cell apoptosis. Continued with our recent work, we found that lncRNA HZ01 (lnc-HZ01) could induce human trophoblast cell apoptosis. In mechanism, lnc-HZ01 up-regulated p53 expression level by suppressing its MDM2-mediated proteasomal degradation. Meanwhile, we found that p53 acted as lnc-HZ01 transcription factor and promoted lnc-HZ01 transcription. Thus, lnc-HZ01 and p53 composed a positive feedback loop in human trophoblast cells. In normal trophoblast cells, relatively low levels of lnc-HZ01 and p53 suppressed p53/caspase-3 apoptosis pathway, giving normal pregnancy. Upon BPDE exposure, BPDE up-regulated the expression levels of lnc-HZ01 and p53, triggered this positive feedback loop, activated the p53/caspase-3 apoptosis pathway, and then induced miscarriage. Collectively, we discovered new mechanism by which lnc-HZ01 regulated BPDE-induced human trophoblast cell apoptosis, providing scientific basis for the diagnosis and treatment of unexplained recurrent miscarriage.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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