Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m<sup>6</sup>A mRNA Methylation through Targeting the <i>Camk1db</i>/ERK Pathway in Zebrafish-Hepatocytes

Berberine (BBR) ameliorates cellular oxidative stress, apoptosis and autophagy induced by lipid metabolism disorder, however, the molecular mechanism associated with it is not well known. To study the mechanism, we started with m<sup>6</sup>A methylation modification to investigate its r...

Full description

Bibliographic Details
Main Authors: Meijuan Zhang, Jin Liu, Chengbing Yu, Shangshang Tang, Guangzhen Jiang, Jing Zhang, Hongcai Zhang, Jianxiong Xu, Weina Xu
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/12/2370
_version_ 1797461719312760832
author Meijuan Zhang
Jin Liu
Chengbing Yu
Shangshang Tang
Guangzhen Jiang
Jing Zhang
Hongcai Zhang
Jianxiong Xu
Weina Xu
author_facet Meijuan Zhang
Jin Liu
Chengbing Yu
Shangshang Tang
Guangzhen Jiang
Jing Zhang
Hongcai Zhang
Jianxiong Xu
Weina Xu
author_sort Meijuan Zhang
collection DOAJ
description Berberine (BBR) ameliorates cellular oxidative stress, apoptosis and autophagy induced by lipid metabolism disorder, however, the molecular mechanism associated with it is not well known. To study the mechanism, we started with m<sup>6</sup>A methylation modification to investigate its role in lipid deposition zebrafish hepatocytes (ZFL). The results showed that BBR could change the cellular m<sup>6</sup>A RNA methylation level, increase m<sup>6</sup>A levels of <i>Camk1db</i> gene transcript and alter <i>Camk1db</i> gene mRNA expression. Via knockdown of the <i>Camk1db</i> gene, <i>Camk1db</i> could promote cellular ERK phosphorylation levels. Berberine regulated the expression level of <i>Camk1db</i> mRNA by altering the M<sup>6</sup>A RNA methylation of the Camk1db gene, which further affected the synthesis of calmodulin-dependent protein kinase and activated ERK signaling pathway resulting in changes in downstream physiological indicators including ROS production, cell proliferation, apoptosis and autophagy. In conclusion, berberine could regulate cellular oxidative stress, apoptosis and autophagy by mediating <i>Camk1db</i> m<sup>6</sup>A methylation through the targeting of the <i>Camk1db</i>/ERK pathway in zebrafish-hepatocyte.
first_indexed 2024-03-09T17:24:21Z
format Article
id doaj.art-bce4b9253c4641189450d804082f0c05
institution Directory Open Access Journal
issn 2076-3921
language English
last_indexed 2024-03-09T17:24:21Z
publishDate 2022-11-01
publisher MDPI AG
record_format Article
series Antioxidants
spelling doaj.art-bce4b9253c4641189450d804082f0c052023-11-24T12:56:53ZengMDPI AGAntioxidants2076-39212022-11-011112237010.3390/antiox11122370Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m<sup>6</sup>A mRNA Methylation through Targeting the <i>Camk1db</i>/ERK Pathway in Zebrafish-HepatocytesMeijuan Zhang0Jin Liu1Chengbing Yu2Shangshang Tang3Guangzhen Jiang4Jing Zhang5Hongcai Zhang6Jianxiong Xu7Weina Xu8Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, ChinaShanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, ChinaShanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, ChinaShanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, ChinaKey Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing 210095, ChinaShanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, ChinaShanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, ChinaShanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, ChinaShanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, ChinaBerberine (BBR) ameliorates cellular oxidative stress, apoptosis and autophagy induced by lipid metabolism disorder, however, the molecular mechanism associated with it is not well known. To study the mechanism, we started with m<sup>6</sup>A methylation modification to investigate its role in lipid deposition zebrafish hepatocytes (ZFL). The results showed that BBR could change the cellular m<sup>6</sup>A RNA methylation level, increase m<sup>6</sup>A levels of <i>Camk1db</i> gene transcript and alter <i>Camk1db</i> gene mRNA expression. Via knockdown of the <i>Camk1db</i> gene, <i>Camk1db</i> could promote cellular ERK phosphorylation levels. Berberine regulated the expression level of <i>Camk1db</i> mRNA by altering the M<sup>6</sup>A RNA methylation of the Camk1db gene, which further affected the synthesis of calmodulin-dependent protein kinase and activated ERK signaling pathway resulting in changes in downstream physiological indicators including ROS production, cell proliferation, apoptosis and autophagy. In conclusion, berberine could regulate cellular oxidative stress, apoptosis and autophagy by mediating <i>Camk1db</i> m<sup>6</sup>A methylation through the targeting of the <i>Camk1db</i>/ERK pathway in zebrafish-hepatocyte.https://www.mdpi.com/2076-3921/11/12/2370berberinem<sup>6</sup>A methylation<i>Camk1db</i>ERKzebrafish hepatocytes (ZFL)
spellingShingle Meijuan Zhang
Jin Liu
Chengbing Yu
Shangshang Tang
Guangzhen Jiang
Jing Zhang
Hongcai Zhang
Jianxiong Xu
Weina Xu
Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m<sup>6</sup>A mRNA Methylation through Targeting the <i>Camk1db</i>/ERK Pathway in Zebrafish-Hepatocytes
Antioxidants
berberine
m<sup>6</sup>A methylation
<i>Camk1db</i>
ERK
zebrafish hepatocytes (ZFL)
title Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m<sup>6</sup>A mRNA Methylation through Targeting the <i>Camk1db</i>/ERK Pathway in Zebrafish-Hepatocytes
title_full Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m<sup>6</sup>A mRNA Methylation through Targeting the <i>Camk1db</i>/ERK Pathway in Zebrafish-Hepatocytes
title_fullStr Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m<sup>6</sup>A mRNA Methylation through Targeting the <i>Camk1db</i>/ERK Pathway in Zebrafish-Hepatocytes
title_full_unstemmed Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m<sup>6</sup>A mRNA Methylation through Targeting the <i>Camk1db</i>/ERK Pathway in Zebrafish-Hepatocytes
title_short Berberine Regulation of Cellular Oxidative Stress, Apoptosis and Autophagy by Modulation of m<sup>6</sup>A mRNA Methylation through Targeting the <i>Camk1db</i>/ERK Pathway in Zebrafish-Hepatocytes
title_sort berberine regulation of cellular oxidative stress apoptosis and autophagy by modulation of m sup 6 sup a mrna methylation through targeting the i camk1db i erk pathway in zebrafish hepatocytes
topic berberine
m<sup>6</sup>A methylation
<i>Camk1db</i>
ERK
zebrafish hepatocytes (ZFL)
url https://www.mdpi.com/2076-3921/11/12/2370
work_keys_str_mv AT meijuanzhang berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes
AT jinliu berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes
AT chengbingyu berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes
AT shangshangtang berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes
AT guangzhenjiang berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes
AT jingzhang berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes
AT hongcaizhang berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes
AT jianxiongxu berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes
AT weinaxu berberineregulationofcellularoxidativestressapoptosisandautophagybymodulationofmsup6supamrnamethylationthroughtargetingtheicamk1dbierkpathwayinzebrafishhepatocytes