Journal
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
Volume 35, Issue 10, Pages -Publisher
WILEY
DOI: 10.1002/jbt.22874
Keywords
AKT; mTOR signaling pathway; apoptosis; autophagy; hepatocyte; paclobutrazol
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Funding
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2017-I2M-1-013]
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The study demonstrated that exposure to PBZ results in inhibition of cell viability, increased oxidative stress, and apoptosis in HepaRG hepatocytes. The mechanism involves the AMPK/mTOR signaling pathway, leading to impaired autophagy and ultimately cell apoptosis.
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 mu M) 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.
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