The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure

Abstract Background Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in premature infants, characterized by alveolar dysplasia and pulmonary microvascular remodeling. In the present study, we have investigated the functional roles of ubiquitin proteasome pathway (UPP) in...

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Autores principales:	Yue Zhu, Huimin Ju, Hongyan Lu, Wei Tang, Junying Lu, Qiuxia Wang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Bronchopulmonary dysplasia Endoplasmic reticulum stress Ubiquitin proteasome pathway Alveolar epithelial type II cells Apoptosis Diseases of the respiratory system RC705-779
Acceso en línea:	https://doaj.org/article/9e28175e75da43d3b0e8a852f13ffd60
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spelling	oai:doaj.org-article:9e28175e75da43d3b0e8a852f13ffd602021-11-28T12:36:27ZThe function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure10.1186/s12890-021-01751-91471-2466https://doaj.org/article/9e28175e75da43d3b0e8a852f13ffd602021-11-01T00:00:00Zhttps://doi.org/10.1186/s12890-021-01751-9https://doaj.org/toc/1471-2466Abstract Background Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in premature infants, characterized by alveolar dysplasia and pulmonary microvascular remodeling. In the present study, we have investigated the functional roles of ubiquitin proteasome pathway (UPP) in BPD, and its relationship with endoplasmic reticulum stress (ERS) mediated type II alveolar epithelial cell (AECII) apoptosis. Methods A hyperoxia-induced BPD rat model was constructed and the pathologic changes of lung tissues were evaluated by hematoxylin–eosin staining. Cell apoptosis and protein expression were determined by TUNEL assay and Western blotting, respectively. Further reagent kit with specific fluorescent substrate was utilized to measure the activity of 20 s proteasome. Meanwhile, AECII were cultured in vitro and exposed to hyperoxia. AECII apoptosis were measured by flow cytometry. In contrast, MG132 treatment was induced to explore UPP during hyperoxia exposure on AECII apoptosis and ERS sensors expression. Results A significant increase in apoptosis and total ubiquitinated proteins expression were observed in BPD rats and AECII culture, and the change of UPP was associated with ERS. In order to confirm the role of UPP in AECII apoptosis of BPD, AECII cells were treated by MG132 with the concentration of 10 μmol/L under hyperoxia exposure. We found that the proteins expression of glucose-regulated protein 78 (GRP-78), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), as well as AECII apoptosis were increased following MG132 treatment. Furthermore, the relatively up-regulated in the levels of total ubiquitinated proteins expression and 20 s proteasome activity were correlated with increased ERS sensors expression. Conclusions Our findings indicate that UPP may participate in the ERS-induced AECII apoptosis under hyperoxia condition.Yue ZhuHuimin JuHongyan LuWei TangJunying LuQiuxia WangBMCarticleBronchopulmonary dysplasiaEndoplasmic reticulum stressUbiquitin proteasome pathwayAlveolar epithelial type II cellsApoptosisDiseases of the respiratory systemRC705-779ENBMC Pulmonary Medicine, Vol 21, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bronchopulmonary dysplasia Endoplasmic reticulum stress Ubiquitin proteasome pathway Alveolar epithelial type II cells Apoptosis Diseases of the respiratory system RC705-779
spellingShingle	Bronchopulmonary dysplasia Endoplasmic reticulum stress Ubiquitin proteasome pathway Alveolar epithelial type II cells Apoptosis Diseases of the respiratory system RC705-779 Yue Zhu Huimin Ju Hongyan Lu Wei Tang Junying Lu Qiuxia Wang The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure
description	Abstract Background Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in premature infants, characterized by alveolar dysplasia and pulmonary microvascular remodeling. In the present study, we have investigated the functional roles of ubiquitin proteasome pathway (UPP) in BPD, and its relationship with endoplasmic reticulum stress (ERS) mediated type II alveolar epithelial cell (AECII) apoptosis. Methods A hyperoxia-induced BPD rat model was constructed and the pathologic changes of lung tissues were evaluated by hematoxylin–eosin staining. Cell apoptosis and protein expression were determined by TUNEL assay and Western blotting, respectively. Further reagent kit with specific fluorescent substrate was utilized to measure the activity of 20 s proteasome. Meanwhile, AECII were cultured in vitro and exposed to hyperoxia. AECII apoptosis were measured by flow cytometry. In contrast, MG132 treatment was induced to explore UPP during hyperoxia exposure on AECII apoptosis and ERS sensors expression. Results A significant increase in apoptosis and total ubiquitinated proteins expression were observed in BPD rats and AECII culture, and the change of UPP was associated with ERS. In order to confirm the role of UPP in AECII apoptosis of BPD, AECII cells were treated by MG132 with the concentration of 10 μmol/L under hyperoxia exposure. We found that the proteins expression of glucose-regulated protein 78 (GRP-78), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), as well as AECII apoptosis were increased following MG132 treatment. Furthermore, the relatively up-regulated in the levels of total ubiquitinated proteins expression and 20 s proteasome activity were correlated with increased ERS sensors expression. Conclusions Our findings indicate that UPP may participate in the ERS-induced AECII apoptosis under hyperoxia condition.
format	article
author	Yue Zhu Huimin Ju Hongyan Lu Wei Tang Junying Lu Qiuxia Wang
author_facet	Yue Zhu Huimin Ju Hongyan Lu Wei Tang Junying Lu Qiuxia Wang
author_sort	Yue Zhu
title	The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure
title_short	The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure
title_full	The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure
title_fullStr	The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure
title_full_unstemmed	The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure
title_sort	function role of ubiquitin proteasome pathway in the er stress-induced aecii apoptosis during hyperoxia exposure
publisher	BMC
publishDate	2021
url	https://doaj.org/article/9e28175e75da43d3b0e8a852f13ffd60
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The function role of ubiquitin proteasome pathway in the ER stress-induced AECII apoptosis during hyperoxia exposure

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