Fig. 5: TCA cycle remodeling promotes PD by increasing H3K4me3 levels.

A Schematic diagram of TCA cycle metabolites regulating histone demethylation. The changing trends of some metabolic enzymes or metabolites are derived from manual annotation of metabolomics data or analysis results of in vitro experiments. B Volcano plot showing serum differential metabolites between early and late stages of PD. α-KG level (C), fumarate level (D), and α-KG/fumarate ratio (E) in PD cell model. The upper and lower boundary in the plot indicates the upper and lower quantiles, the line inside the plot the median; n = 15 biological replicates. F Representative images (left) and expression level analysis (right) of H3K4me2 and H3K4me3 protein expression in PD cell model. Data are mean ± SEM; n ≥ 4 biological replicates. G Representative images (left) and expression level analysis (right) of H3K4me2 and H3K4me3 protein expression in PD cell model treated with different concentrations of CPI-455. Data are mean ± SEM; n = 4 biological replicates. H Cell viability analysis of PD cell model treated with OICR-9429 at the indicated concentrations. Data are mean ± SEM; n = 4 biological replicates. I Schematic diagram of the establishment of the OICR-9429-treated PD cell model. J Representative images (left) and expression level analysis (right) of H3K4me2 and H3K4me3 protein expression in OICR-9429-treated PD cell model. Data are mean ± SEM; n = 5 biological replicates. K Bright field images of OICR-9429-treated PD cell model. L Representative images (left) and ratios (right) of TUNEL⁺ cells in the OICR-9429-treated PD cell model. Data are mean ± SEM; n = 5 biological replicates.