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Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways

Age-related hearing loss, also termed central presbycusis, is a progressive neurodegenerative disease; it is a devastating disorder that severely affects the quality of life of elderly individuals. Substantial evidence has indicated that oxidative stress and associated protein folding dysfunction ha...

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Autores principales: Cai, Hua, Han, Baoai, Hu, Yujuan, Zhao, Xueyan, He, Zuhong, Chen, Xubo, Sun, Haiying, Yuan, Jie, Li, Yongqin, Yang, Xiuping, Kong, Wen, Kong, Wei-Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015132/
https://www.ncbi.nlm.nih.gov/pubmed/31922237
http://dx.doi.org/10.3892/ijmm.2020.4453
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author Cai, Hua
Han, Baoai
Hu, Yujuan
Zhao, Xueyan
He, Zuhong
Chen, Xubo
Sun, Haiying
Yuan, Jie
Li, Yongqin
Yang, Xiuping
Kong, Wen
Kong, Wei-Jia
author_facet Cai, Hua
Han, Baoai
Hu, Yujuan
Zhao, Xueyan
He, Zuhong
Chen, Xubo
Sun, Haiying
Yuan, Jie
Li, Yongqin
Yang, Xiuping
Kong, Wen
Kong, Wei-Jia
author_sort Cai, Hua
collection PubMed
description Age-related hearing loss, also termed central presbycusis, is a progressive neurodegenerative disease; it is a devastating disorder that severely affects the quality of life of elderly individuals. Substantial evidence has indicated that oxidative stress and associated protein folding dysfunction have a marked influence on neurodegenerative diseases. In this study, we aimed to cells to investigate whether metformin protects against age-related pathologies and to elucidate the underlying mechanisms; specifically, we focused on the role of unfolded protein response (UPR) via the AMPK/ERK1/2 signaling pathways. For this purpose, the biguanide compound, metformin, a medication widely used in the treatment of type 2 diabetes, was administered to rats in a model of mimetic aging. In addition, senescent PC12 were treated with metformin. Although it has been well established that UPR signaling is activated in response to cellular stress and is associated with the pathogenesis of neuronal deterioration, the detailed functions of the UPR in the auditory cortex remain unclear. We found that metformin treatment markedly affected the UPR and the AMPK/ERK1/2 signaling pathway, and maintained the auditory brainstem response (ABR) threshold during the aging process. The results indicated that the regulation of the UPR and AMPK/ERK1/2 signaling pathway by metformin significantly attenuated hearing loss, cell apoptosis and age-related neurodegeneration. Reversing these harmful effects through the use of metformin suggests its involvement in restoring the antioxidant status and protein homeostasis related to the underlying pathology of presbycusis. The findings of this study may provide a better approach for the treatment of age-related neurodegeneration diseases.
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spelling pubmed-70151322020-02-15 Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways Cai, Hua Han, Baoai Hu, Yujuan Zhao, Xueyan He, Zuhong Chen, Xubo Sun, Haiying Yuan, Jie Li, Yongqin Yang, Xiuping Kong, Wen Kong, Wei-Jia Int J Mol Med Articles Age-related hearing loss, also termed central presbycusis, is a progressive neurodegenerative disease; it is a devastating disorder that severely affects the quality of life of elderly individuals. Substantial evidence has indicated that oxidative stress and associated protein folding dysfunction have a marked influence on neurodegenerative diseases. In this study, we aimed to cells to investigate whether metformin protects against age-related pathologies and to elucidate the underlying mechanisms; specifically, we focused on the role of unfolded protein response (UPR) via the AMPK/ERK1/2 signaling pathways. For this purpose, the biguanide compound, metformin, a medication widely used in the treatment of type 2 diabetes, was administered to rats in a model of mimetic aging. In addition, senescent PC12 were treated with metformin. Although it has been well established that UPR signaling is activated in response to cellular stress and is associated with the pathogenesis of neuronal deterioration, the detailed functions of the UPR in the auditory cortex remain unclear. We found that metformin treatment markedly affected the UPR and the AMPK/ERK1/2 signaling pathway, and maintained the auditory brainstem response (ABR) threshold during the aging process. The results indicated that the regulation of the UPR and AMPK/ERK1/2 signaling pathway by metformin significantly attenuated hearing loss, cell apoptosis and age-related neurodegeneration. Reversing these harmful effects through the use of metformin suggests its involvement in restoring the antioxidant status and protein homeostasis related to the underlying pathology of presbycusis. The findings of this study may provide a better approach for the treatment of age-related neurodegeneration diseases. D.A. Spandidos 2020-03 2020-01-08 /pmc/articles/PMC7015132/ /pubmed/31922237 http://dx.doi.org/10.3892/ijmm.2020.4453 Text en Copyright: © Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Cai, Hua
Han, Baoai
Hu, Yujuan
Zhao, Xueyan
He, Zuhong
Chen, Xubo
Sun, Haiying
Yuan, Jie
Li, Yongqin
Yang, Xiuping
Kong, Wen
Kong, Wei-Jia
Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways
title Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways
title_full Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways
title_fullStr Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways
title_full_unstemmed Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways
title_short Metformin attenuates the D-galactose-induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways
title_sort metformin attenuates the d-galactose-induced aging process via the upr through the ampk/erk1/2 signaling pathways
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015132/
https://www.ncbi.nlm.nih.gov/pubmed/31922237
http://dx.doi.org/10.3892/ijmm.2020.4453
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