Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells

Preeclampsia (PE) is a pregnancy disorder characterized by excessive trophoblast cell death. This study aims to explore the exact mechanism of the ubiquitination level of FUN14 domain containing 1 (FUNDC1) in mitophagy and injury in hypoxic trophoblast cells. In this study, HTR-8/SVneo trophoblast c...

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Autores principales: GuoQing Chen, Lu Chen, Yan Huang, XiongShan Zhu, YuanLan Yu
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Lenguaje:EN
Publicado: Taylor & Francis Group 2021
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Acceso en línea:https://doaj.org/article/e7b7debb99a64b45a4f2e00a99471e3c
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spelling oai:doaj.org-article:e7b7debb99a64b45a4f2e00a99471e3c2021-11-04T15:51:54ZIncreased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells2165-59792165-598710.1080/21655979.2021.1997132https://doaj.org/article/e7b7debb99a64b45a4f2e00a99471e3c2021-10-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1997132https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Preeclampsia (PE) is a pregnancy disorder characterized by excessive trophoblast cell death. This study aims to explore the exact mechanism of the ubiquitination level of FUN14 domain containing 1 (FUNDC1) in mitophagy and injury in hypoxic trophoblast cells. In this study, HTR-8/SVneo trophoblast cells were cultured under normoxic and hypoxic conditions and PE mouse model was established. We found low ubiquitination level of FUNDC1 in hypoxic trophoblast cells and placenta of pregnant women with PE. Proteasome inhibitor MG-132 and protease activator MF-094 were added into HTR-8/SVneo trophoblast cells. Proteasome inhibitor MG-132 decreased FUNDC1 ubiquitination level while protease activator MF-094 increased FUNDC1 ubiquitination level. Inhibition of FUNDC1 ubiquitination promoted mitophagy and mitochondrial membrane potential (Δψm) in normoxic trophoblast cells, increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased levels of glutathione (GSH) and superoxide dismutase (SOD). In addition, FUNDC1 ubiquitination alleviated cell injury in PE mice in vivo. In conclusion, increased FUNDC1 ubiquitination level inhibited mitophagy and Δψm changes in hypoxic trophoblast cells, and thus alleviated oxidative injury.GuoQing ChenLu ChenYan HuangXiongShan ZhuYuanLan YuTaylor & Francis Grouparticlepreeclampsiaubiquitinationfundc1mitophagytrophoblast cellscell injuryBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution DOAJ
collection DOAJ
language EN
topic preeclampsia
ubiquitination
fundc1
mitophagy
trophoblast cells
cell injury
Biotechnology
TP248.13-248.65
spellingShingle preeclampsia
ubiquitination
fundc1
mitophagy
trophoblast cells
cell injury
Biotechnology
TP248.13-248.65
GuoQing Chen
Lu Chen
Yan Huang
XiongShan Zhu
YuanLan Yu
Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells
description Preeclampsia (PE) is a pregnancy disorder characterized by excessive trophoblast cell death. This study aims to explore the exact mechanism of the ubiquitination level of FUN14 domain containing 1 (FUNDC1) in mitophagy and injury in hypoxic trophoblast cells. In this study, HTR-8/SVneo trophoblast cells were cultured under normoxic and hypoxic conditions and PE mouse model was established. We found low ubiquitination level of FUNDC1 in hypoxic trophoblast cells and placenta of pregnant women with PE. Proteasome inhibitor MG-132 and protease activator MF-094 were added into HTR-8/SVneo trophoblast cells. Proteasome inhibitor MG-132 decreased FUNDC1 ubiquitination level while protease activator MF-094 increased FUNDC1 ubiquitination level. Inhibition of FUNDC1 ubiquitination promoted mitophagy and mitochondrial membrane potential (Δψm) in normoxic trophoblast cells, increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased levels of glutathione (GSH) and superoxide dismutase (SOD). In addition, FUNDC1 ubiquitination alleviated cell injury in PE mice in vivo. In conclusion, increased FUNDC1 ubiquitination level inhibited mitophagy and Δψm changes in hypoxic trophoblast cells, and thus alleviated oxidative injury.
format article
author GuoQing Chen
Lu Chen
Yan Huang
XiongShan Zhu
YuanLan Yu
author_facet GuoQing Chen
Lu Chen
Yan Huang
XiongShan Zhu
YuanLan Yu
author_sort GuoQing Chen
title Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells
title_short Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells
title_full Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells
title_fullStr Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells
title_full_unstemmed Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells
title_sort increased fun14 domain containing 1 (fundc1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/e7b7debb99a64b45a4f2e00a99471e3c
work_keys_str_mv AT guoqingchen increasedfun14domaincontaining1fundc1ubiquitinationlevelinhibitsmitophagyandalleviatestheinjuryinhypoxiainducedtrophoblastcells
AT luchen increasedfun14domaincontaining1fundc1ubiquitinationlevelinhibitsmitophagyandalleviatestheinjuryinhypoxiainducedtrophoblastcells
AT yanhuang increasedfun14domaincontaining1fundc1ubiquitinationlevelinhibitsmitophagyandalleviatestheinjuryinhypoxiainducedtrophoblastcells
AT xiongshanzhu increasedfun14domaincontaining1fundc1ubiquitinationlevelinhibitsmitophagyandalleviatestheinjuryinhypoxiainducedtrophoblastcells
AT yuanlanyu increasedfun14domaincontaining1fundc1ubiquitinationlevelinhibitsmitophagyandalleviatestheinjuryinhypoxiainducedtrophoblastcells
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