Affiliation:
1. College of Chemistry and Chemical Engineering Zhongkai University of Agriculture and Engineering Dongsha Street 24 Guangzhou 510225 Guangdong China
2. College of Light Industry and Food Technology, Zhongkai University of Agriculture and Engineering Dongsha Street 24 Guangzhou 510225 Guangdong China
3. School of Economics and Statistics, Guangdong Provincial Key Laboratory of Optoelectronic Materials and Sensor Components, Guangzhou Key Laboratory of Sensing Materials and Devices, Centre for Advanced Analytical Science Guangzhou University Guangzhou 510006 Guangdong China
Abstract
SummaryBetaine is a natural antioxidant lacking the ability to scavenge free radicals. Although it has been shown to exert antioxidant function by enhancing the expression of antioxidant enzymes, its mechanism has not yet been elucidated. This study explored the role and mechanism of the transcription factor NF‐E2‐associated factor 2 (Nrf2)‐Kelch‐like epichlorohydrin‐associated Protein 1 (Keap1) antioxidant reaction element (ARE) pathway in betaine‐mediated enhancement of antioxidant enzyme expression. Results derived from real‐time quantitative PCR, Western blot, quantitative methylation‐specific PCR, and inhibitors assay experiments showed that betaine activated the Nrf2‐Keap1‐ARE pathway, leading to an increase in the mRNA level of superoxide dismutase, glutathione peroxidase, and heme oxygenase‐1. The mechanism may involve betaine's promotion of DNA methyltransferase expression, resulting in increased methylation of Keap1 DNA promoter, which ultimately reduces the level of Keap1 mRNA. Therefore, betaine can directly activate the Nrf2‐Keap1‐ARE pathway by increasing the methylation level of Keap1 DNA promoter, thereby improving the expression of antioxidant enzymes. This study will contribute to unveiling a new antioxidant mechanism for betaine.
Funder
Basic and Applied Basic Research Foundation of Guangdong Province
National Natural Science Foundation of China