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PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway
A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273041/ https://www.ncbi.nlm.nih.gov/pubmed/34285767 http://dx.doi.org/10.1155/2021/9980444 |
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author | Zhang, Yanzhuo Lv, Zhe Liu, Yudong Cao, Huan Yang, Jianwang Wang, Baoshan |
author_facet | Zhang, Yanzhuo Lv, Zhe Liu, Yudong Cao, Huan Yang, Jianwang Wang, Baoshan |
author_sort | Zhang, Yanzhuo |
collection | PubMed |
description | A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by H(2)O(2) was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under H(2)O(2) and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence. |
format | Online Article Text |
id | pubmed-8273041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-82730412021-07-19 PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway Zhang, Yanzhuo Lv, Zhe Liu, Yudong Cao, Huan Yang, Jianwang Wang, Baoshan Oxid Med Cell Longev Research Article A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by H(2)O(2) was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under H(2)O(2) and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence. Hindawi 2021-06-02 /pmc/articles/PMC8273041/ /pubmed/34285767 http://dx.doi.org/10.1155/2021/9980444 Text en Copyright © 2021 Yanzhuo Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhang, Yanzhuo Lv, Zhe Liu, Yudong Cao, Huan Yang, Jianwang Wang, Baoshan PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway |
title | PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway |
title_full | PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway |
title_fullStr | PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway |
title_full_unstemmed | PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway |
title_short | PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway |
title_sort | pin1 protects hair cells and auditory hei-oc1 cells against senescence by inhibiting the pi3k/akt/mtor pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273041/ https://www.ncbi.nlm.nih.gov/pubmed/34285767 http://dx.doi.org/10.1155/2021/9980444 |
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