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Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury

BACKGROUND: As a novel pathophysiological characteristic of obstructive sleep apnea, intermittent hypoxia (IH) contributes to human renal tubular epithelial cells impairment. The underlying pathological mechanisms remain unrevealed. The present study aimed to evaluate the influence of Bcl-2 19-kDa i...

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Autores principales: Zhang, Xiao-Bin, Chen, Gong-Ping, Huang, Mao-Hong, Chen, Xiang-Xing, Zhan, Feng-Fu, He, Xiu-Zhen, Cai, Ling, Zeng, Hui-Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295414/
https://www.ncbi.nlm.nih.gov/pubmed/35836356
http://dx.doi.org/10.12659/MSM.936760
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author Zhang, Xiao-Bin
Chen, Gong-Ping
Huang, Mao-Hong
Chen, Xiang-Xing
Zhan, Feng-Fu
He, Xiu-Zhen
Cai, Ling
Zeng, Hui-Qing
author_facet Zhang, Xiao-Bin
Chen, Gong-Ping
Huang, Mao-Hong
Chen, Xiang-Xing
Zhan, Feng-Fu
He, Xiu-Zhen
Cai, Ling
Zeng, Hui-Qing
author_sort Zhang, Xiao-Bin
collection PubMed
description BACKGROUND: As a novel pathophysiological characteristic of obstructive sleep apnea, intermittent hypoxia (IH) contributes to human renal tubular epithelial cells impairment. The underlying pathological mechanisms remain unrevealed. The present study aimed to evaluate the influence of Bcl-2 19-kDa interacting protein 3 (BNIP3)-mediated mitophagy on IH-induced renal tubular epithelial cell impairment. MATERIAL/METHODS: Human kidney proximal tubular (HK-2) cells were exposed to IH condition. IH cycles were as follows: 21% oxygen for 25 min, 21% descended to 1% for 35 min, 1% oxygen sustaining for 35 min, and 1% ascended to 21% for 25 min. The IH exposure lasted 24 h with 12 cycles of hypoxia and re-oxygenation. Both the siBNIP3 and BNIP3 vector were transfected to cells. Cell viability and apoptosis, mitochondrial morphology and function, and mitophagy were detected by cell counting kit-8, flow cytometry and TUNEL staining, transmission electron microscopy, western blotting, and immunofluorescence, respectively. RESULTS: In the IH-induced HK-2 cells, inhibition of BNIP3 further aggravated mitochondrial structure damage, and decreased mitophagy level, leading to increased cell apoptosis and decreased cell viability. While overexpression of BNIP3 enhanced mitophagy, which protected mitochondrial structure, it can decrease cell death in HK-2 cells exposed to IH. CONCLUSIONS: The present study showed that BNIP3-mediated mitophagy plays a protective role against IH-induced renal tubular epithelial cell impairment.
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spelling pubmed-92954142022-07-28 Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury Zhang, Xiao-Bin Chen, Gong-Ping Huang, Mao-Hong Chen, Xiang-Xing Zhan, Feng-Fu He, Xiu-Zhen Cai, Ling Zeng, Hui-Qing Med Sci Monit Lab/In Vitro Research BACKGROUND: As a novel pathophysiological characteristic of obstructive sleep apnea, intermittent hypoxia (IH) contributes to human renal tubular epithelial cells impairment. The underlying pathological mechanisms remain unrevealed. The present study aimed to evaluate the influence of Bcl-2 19-kDa interacting protein 3 (BNIP3)-mediated mitophagy on IH-induced renal tubular epithelial cell impairment. MATERIAL/METHODS: Human kidney proximal tubular (HK-2) cells were exposed to IH condition. IH cycles were as follows: 21% oxygen for 25 min, 21% descended to 1% for 35 min, 1% oxygen sustaining for 35 min, and 1% ascended to 21% for 25 min. The IH exposure lasted 24 h with 12 cycles of hypoxia and re-oxygenation. Both the siBNIP3 and BNIP3 vector were transfected to cells. Cell viability and apoptosis, mitochondrial morphology and function, and mitophagy were detected by cell counting kit-8, flow cytometry and TUNEL staining, transmission electron microscopy, western blotting, and immunofluorescence, respectively. RESULTS: In the IH-induced HK-2 cells, inhibition of BNIP3 further aggravated mitochondrial structure damage, and decreased mitophagy level, leading to increased cell apoptosis and decreased cell viability. While overexpression of BNIP3 enhanced mitophagy, which protected mitochondrial structure, it can decrease cell death in HK-2 cells exposed to IH. CONCLUSIONS: The present study showed that BNIP3-mediated mitophagy plays a protective role against IH-induced renal tubular epithelial cell impairment. International Scientific Literature, Inc. 2022-07-15 /pmc/articles/PMC9295414/ /pubmed/35836356 http://dx.doi.org/10.12659/MSM.936760 Text en © Med Sci Monit, 2022 https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Zhang, Xiao-Bin
Chen, Gong-Ping
Huang, Mao-Hong
Chen, Xiang-Xing
Zhan, Feng-Fu
He, Xiu-Zhen
Cai, Ling
Zeng, Hui-Qing
Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury
title Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury
title_full Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury
title_fullStr Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury
title_full_unstemmed Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury
title_short Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury
title_sort bcl-2 19-kda interacting protein 3 (bnip3)-mediated mitophagy attenuates intermittent hypoxia-induced human renal tubular epithelial cell injury
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295414/
https://www.ncbi.nlm.nih.gov/pubmed/35836356
http://dx.doi.org/10.12659/MSM.936760
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