PXR Activation Relieves Deoxynivalenol-Induced Liver Oxidative Stress Via Malat1 LncRNA m⁶A Demethylation.

ABSTRACT: Deoxynivalenol (DON) is a prevalent toxin causing severe liver damage through hepatocellular oxidative stress. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, the unique role of the xenobiotic metabolism factor pregnane X receptor (PXR) in mediating DON-induced hepatocellular oxidative stress is investigated. Treatment with the PXR agonist 3-indole-propionic acid (IPA) alleviates DON-induced oxidative stress and liver injury both in vitro and in vivo. Mechanistically, it is discovered for the first time that PXR agonist IPA directly transactivates the m⁶A demethylase FTO expression, leading to site-specific demethylation and decreased abundance of YTHDC1-bound Malat1 lncRNA at single-nucleotide resolution. The diminished m⁶

SUBMITTER: Feng Y 

PROVIDER: S-EPMC11220637 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature