CircRNA_1156 Attenuates Neodymium Nitrate-Induced Hepatocyte Ferroptosis by Inhibiting the ACSL4/PKCβII Signaling Pathway

  • 0Institute of Chemical Safety Evaluation, State Environmental Protection Key Laboratory of Health Impact Assessment on New Environmental Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China.

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Summary

This summary is machine-generated.

CircRNA_1156 inhibits neodymium nitrate-induced ferroptosis in liver cells. This circular RNA protects against rare earth element compound hepatotoxicity by downregulating the ACSL4/PKCβII pathway.

Area Of Science

  • Biochemistry
  • Cell Biology
  • Toxicology

Background

  • Ferroptosis, a lipid peroxidation-driven cell death, contributes to liver disease pathogenesis.
  • Rare earth element compounds, like neodymium nitrate, can induce hepatotoxicity.
  • Circular RNAs (circRNAs) are emerging as critical regulators in cellular processes.

Purpose Of The Study

  • To investigate the role of circRNA_1156 in neodymium nitrate-induced ferroptosis in hepatocytes.
  • To elucidate the molecular mechanisms by which circRNA_1156 affects Nd(NO3)3-induced liver injury.
  • To explore circRNA_1156 as a potential therapeutic target for rare earth element compound hepatotoxicity.

Main Methods

  • In vitro studies using AML12 hepatocytes exposed to Nd(NO3)3.
  • In vivo studies involving chronic Nd(NO3)3 administration in animal models.
  • Assessment of cell viability, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) levels.
  • Analysis of ACSL4 and PKCβII expression, hepatic iron deposition, and mitochondrial damage.
  • Overexpression of circRNA_1156 to evaluate its protective effects.

Main Results

  • Nd(NO3)3 exposure reduced hepatocyte viability, increased oxidative stress markers (ROS, MDA), and depleted GSH.
  • Overexpression of circRNA_1156 reversed Nd(NO3)3-induced cellular damage and suppressed ACSL4/PKCβII expression.
  • In vivo, Nd(NO3)3 induced hepatic iron deposition, mitochondrial damage, and activated the ACSL4/PKCβII pathway.
  • CircRNA_1156 overexpression significantly ameliorated these in vivo adverse effects.

Conclusions

  • CircRNA_1156 acts as a novel inhibitor of neodymium nitrate-induced ferroptosis.
  • The protective mechanism involves the downregulation of the ACSL4/PKCβII pathway.
  • CircRNA_1156 holds therapeutic potential for treating liver injury caused by rare earth element compounds.