Paclobutrazol exposure induces apoptosis and impairs autophagy in hepatocytes via the AMPK/mTOR signaling pathway

J Biochem Mol Toxicol. 2021 Oct;35(10):e22874. doi: 10.1002/jbt.22874. Epub 2021 Aug 5.

Abstract

Paclobutrazol (PBZ), one of the most widely used plant growth retardants in vegetables, fruits, and traditional Chinese medicine ingredients, exposes people to adverse events. In this study, HepaRG hepatocytes were cultured and exposed to PBZ (360 μM) in vitro to determine its mechanism. Results showed that PBZ exposure inhibited cell viability in a time- and dose-dependent manner and increased the oxidative stress and apoptosis ratio in HepaRG cells. These data revealed that the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) has an important role in PBZ-induced cell apoptosis, which is mediated by impaired autophagy and blocked by the AMPK activator. In conclusion, PBZ exposure induces apoptosis and impairs autophagy in hepatocytes via the AMPK/mTOR signaling pathway.

Keywords: AKT/mTOR signaling pathway; apoptosis; autophagy; hepatocyte; paclobutrazol.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Catalase / metabolism
  • Cell Line, Transformed
  • Cell Survival / drug effects
  • Drugs, Chinese Herbal / adverse effects*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Humans
  • Malondialdehyde / metabolism
  • Ophiopogon / chemistry
  • Oxidative Stress / drug effects
  • Phytochemicals / adverse effects*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Superoxide Dismutase / metabolism
  • TOR Serine-Threonine Kinases / metabolism*
  • Triazoles / adverse effects*

Substances

  • Drugs, Chinese Herbal
  • Phytochemicals
  • Reactive Oxygen Species
  • Triazoles
  • Malondialdehyde
  • paclobutrazol
  • Catalase
  • Superoxide Dismutase
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases