Resveratrol-mediated Sirtuin 1 Negative Regulation of Deacetylation of Tet Methylcytosine Dioxygenase 2 in Parkinson’s Patients

Background: Resveratrol (RV) plays a crucial part in regulating the development of the nervous system. Tet methylcytosine dioxygenase 2 (TET2) has an important physiological significance in the nervous system. TET2 pertains to the deoxyribonucleic acid (DNA) hydroxylase family. Sirtuin 1 (SIRT1) plays a part in the development of Parkinson’s disease (PD) in patients. Objectives: This study will verify the effect of RV on SIRT1 activity and analyze whether this effect is related to changes in TET2 expression levels, further exploring its potential molecular mechanisms. Materials and Methods: The SH-SY5Y cells were divided into control, RV treatment, 1-methyl-4-phenylpyridinium (MPP+) treatment, and RV + MPP+ combination treatment groups. Neuron TET2 expression was tested in SH-SY5Y cells treated with SRT1720 or EX-527, and SIRT1 agonists and inhibitors were used to detect TET2 messenger ribonucleic acid (mRNA) levels. After treatment with EX-527 or RV, endogenous acetylated TET2 was measured by coimmunoprecipitation (CO-IP). After treatment with dissolved in dimethyl sulfoxide (DMSO) or EX-527 for 24 h, cells were collected after adding MG-132 to the culture medium to detect protein levels of polyubiquitination. Results: SIRT1 activity is negatively linked to TET2. RV activates endogenous SIRT1 and decreases TET2 levels and cyclindependent kinase inhibitor 2A (CDKN2A) DNA hypermethylation, thereby upregulating pRb. TET2 inhibitors have inhibitory effects on endogenous TET2 enzyme activity. Conclusion: RV alleviates MPP+-induced cell damage by activating SIRT1, confirming a negative correlation between SIRT1 activity and TET2 protein levels, and affects its stability by promoting TET2 deacetylation and ubiquitination degradation, regulating DNA methylation. In addition, SIRT1 regulates TET2 to inhibit cell cycle arrest, affecting neuronal growth and apoptosis. These findings provide a theoretical basis for new treatment methods based on the SIRT1/TET2 pathway, demonstrating the potential of RV in the treatment of PD and bringing new hope for improving patients’ quality of life.