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
Meijuan Zhang,
Jin Liu,
Chengbing Yu,
Shangshang Tang,
Guangzhen Jiang,
Jing Zhang,
Hongcai Zhang,
Jianxiong Xu,
Weina Xu
Affiliations
Meijuan Zhang
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, China
Jin Liu
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, China
Chengbing Yu
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, China
Shangshang Tang
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, China
Guangzhen Jiang
Key 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, China
Jing Zhang
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, China
Hongcai Zhang
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, China
Jianxiong Xu
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, China
Weina Xu
Shanghai Key Laboratory for Veterinary and Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Jiangchuan Road, Shanghai 200240, China
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 m6A methylation modification to investigate its role in lipid deposition zebrafish hepatocytes (ZFL). The results showed that BBR could change the cellular m6A RNA methylation level, increase m6A levels of Camk1db gene transcript and alter Camk1db gene mRNA expression. Via knockdown of the Camk1db gene, Camk1db could promote cellular ERK phosphorylation levels. Berberine regulated the expression level of Camk1db mRNA by altering the M6A 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 Camk1db m6A methylation through the targeting of the Camk1db/ERK pathway in zebrafish-hepatocyte.
