Cargando…

Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway

Oxidative stress has been identified as a major cause of cellular injury in a variety of neurodegenerative disorders. This study aimed to investigate the cytoprotective effects of piceatannol on hydrogen peroxide (H(2)O(2))-induced pheochromocytoma-12 (PC-12) cell damage and explore the underlying m...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Jie, Mai, Peishi, Yang, Zihui, Wang, Zongwei, Yang, Wei, Wang, Ziyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10346636/
https://www.ncbi.nlm.nih.gov/pubmed/37447299
http://dx.doi.org/10.3390/nu15132973
_version_ 1785073359887794176
author Liu, Jie
Mai, Peishi
Yang, Zihui
Wang, Zongwei
Yang, Wei
Wang, Ziyuan
author_facet Liu, Jie
Mai, Peishi
Yang, Zihui
Wang, Zongwei
Yang, Wei
Wang, Ziyuan
author_sort Liu, Jie
collection PubMed
description Oxidative stress has been identified as a major cause of cellular injury in a variety of neurodegenerative disorders. This study aimed to investigate the cytoprotective effects of piceatannol on hydrogen peroxide (H(2)O(2))-induced pheochromocytoma-12 (PC-12) cell damage and explore the underlying mechanisms. Our findings indicated that piceatannol pre-treatment significantly attenuated H(2)O(2)-induced PC-12 cell death. Furthermore, piceatannol effectively improved mitochondrial content and mitochondrial function, including enhancing mitochondrial reactive oxygen species (ROS) elimination capacity and increasing mitochondrial transcription factor (TFAM), peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitochondria Complex IV expression. Meanwhile, piceatannol treatment inhibited mitochondria-mediated autophagy as demonstrated by restoring mitochondrial membrane potential, reducing autophagosome formation and light chain 3B II/I (LC3B II/I) and autophagy-related protein 5 (ATG5) expression level. The protein expression level of SIRT3 was significantly increased by piceatannol in a concentration-dependent manner. However, the cytoprotective effect of piceatannol was dramatically abolished by sirtuin 3 (SIRT3) inhibitor, 3-(1H-1,2,3-Triazol-4-yl) pyridine (3-TYP), which led to an exacerbated mitochondrial dysfunction and autophagy in PC-12 cells under oxidative stress. In addition, the autophagy activator (rapamycin) abrogated the protective effects of piceatannol on PC-12 cell death. These findings demonstrated that piceatannol could alleviate PC-12 cell oxidative damage and mitochondrial dysfunction by inhibiting autophagy via the SIRT3 pathway.
format Online
Article
Text
id pubmed-10346636
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103466362023-07-15 Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway Liu, Jie Mai, Peishi Yang, Zihui Wang, Zongwei Yang, Wei Wang, Ziyuan Nutrients Article Oxidative stress has been identified as a major cause of cellular injury in a variety of neurodegenerative disorders. This study aimed to investigate the cytoprotective effects of piceatannol on hydrogen peroxide (H(2)O(2))-induced pheochromocytoma-12 (PC-12) cell damage and explore the underlying mechanisms. Our findings indicated that piceatannol pre-treatment significantly attenuated H(2)O(2)-induced PC-12 cell death. Furthermore, piceatannol effectively improved mitochondrial content and mitochondrial function, including enhancing mitochondrial reactive oxygen species (ROS) elimination capacity and increasing mitochondrial transcription factor (TFAM), peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitochondria Complex IV expression. Meanwhile, piceatannol treatment inhibited mitochondria-mediated autophagy as demonstrated by restoring mitochondrial membrane potential, reducing autophagosome formation and light chain 3B II/I (LC3B II/I) and autophagy-related protein 5 (ATG5) expression level. The protein expression level of SIRT3 was significantly increased by piceatannol in a concentration-dependent manner. However, the cytoprotective effect of piceatannol was dramatically abolished by sirtuin 3 (SIRT3) inhibitor, 3-(1H-1,2,3-Triazol-4-yl) pyridine (3-TYP), which led to an exacerbated mitochondrial dysfunction and autophagy in PC-12 cells under oxidative stress. In addition, the autophagy activator (rapamycin) abrogated the protective effects of piceatannol on PC-12 cell death. These findings demonstrated that piceatannol could alleviate PC-12 cell oxidative damage and mitochondrial dysfunction by inhibiting autophagy via the SIRT3 pathway. MDPI 2023-06-30 /pmc/articles/PMC10346636/ /pubmed/37447299 http://dx.doi.org/10.3390/nu15132973 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Jie
Mai, Peishi
Yang, Zihui
Wang, Zongwei
Yang, Wei
Wang, Ziyuan
Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway
title Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway
title_full Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway
title_fullStr Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway
title_full_unstemmed Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway
title_short Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway
title_sort piceatannol protects pc-12 cells against oxidative damage and mitochondrial dysfunction by inhibiting autophagy via sirt3 pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10346636/
https://www.ncbi.nlm.nih.gov/pubmed/37447299
http://dx.doi.org/10.3390/nu15132973
work_keys_str_mv AT liujie piceatannolprotectspc12cellsagainstoxidativedamageandmitochondrialdysfunctionbyinhibitingautophagyviasirt3pathway
AT maipeishi piceatannolprotectspc12cellsagainstoxidativedamageandmitochondrialdysfunctionbyinhibitingautophagyviasirt3pathway
AT yangzihui piceatannolprotectspc12cellsagainstoxidativedamageandmitochondrialdysfunctionbyinhibitingautophagyviasirt3pathway
AT wangzongwei piceatannolprotectspc12cellsagainstoxidativedamageandmitochondrialdysfunctionbyinhibitingautophagyviasirt3pathway
AT yangwei piceatannolprotectspc12cellsagainstoxidativedamageandmitochondrialdysfunctionbyinhibitingautophagyviasirt3pathway
AT wangziyuan piceatannolprotectspc12cellsagainstoxidativedamageandmitochondrialdysfunctionbyinhibitingautophagyviasirt3pathway