Exploring the Impact of Sirt1 on Oxidative Stress and Inflammation in Alzheimers Disease Cell Models Through p53 Regulation: A Preliminary Study

Abstract

Objective: Sirtuin (Sirt), an NAD+-dependent deacetylase, is known for its regulatory role in cellular metabolism, aging, and disease. Evidence suggests that Sirt1 is linked to the pathogenesis of Alzheimers disease (AD). This study aims to elucidate how Sirt1 regulates p53, focusing on the AD cell models inflammatory response and oxidative stress. Methods: Cell experiments were divided into three groups: the Control group, the Model group, and the Resveratrol group. The Control group underwent regular media changes, while the Model group was exposed to a mixture of Amyloid-beta (Aβ) oligomers (0.55 μM) and IBO (0.6 μM) for 48 hours to create an AD model. The Resveratrol group was treated similarly to the Model group but was exposed to 10 μM resveratrol for 24 hours before assessment. Through immunoprecipitation, proteomic analysis, and Venn analysis, Sirt1s acetylation substrate was identified as p53. An AD cell model was established using BV2 microglial cells, and the effects of Sirt1 on oxidative stress and inflammation, mediated by p53 regulation, were determined using immunofluorescence, Enzyme-linked immunosorbent assay (ELISA), Western Blot (WB), and qPCR technologies. Results: This study identifies p53 as a substrate for Sirt1 acetylation, corroborated through immunoprecipitation experiments and proteomic analysis. In microglial cells, the activation level in the Model group was significantly higher than in the Control and Resveratrol groups (p < 0.01). ELISA results revealed a significant increase in the expression levels of various substances in the AD Model group compared to the Control group, with a notable decrease in superoxide dismutase (SOD) expression (p < 0.01). However, these were improved in the Resveratrol group. The analysis of WB and qPCR indicated that Sirt1 decreased significantly in the Model group, while E74-like factor 1 (Elf-1), Nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3), Acetylated p53 (acetyl-p53) and other indicators increased significantly (p < 0.01). Compared with the Model group, Sirt1 in the Resveratrol group increased significantly (p < 0.01), and the indicators such as Elf-1, NLRP3 decreased. There was no significant difference in the mRNA transcription level of p53 among the Control group, Model group and Resveratrol group (p > 0.05). Conclusions: The results of this study suggest that Sirt1 may affect the inflammatory response and oxidative stress in AD cell models by regulating p53.