PMID- 34351037
OWN - NLM
STAT- MEDLINE
DCOM- 20220203
LR  - 20220203
IS  - 1099-0461 (Electronic)
IS  - 1095-6670 (Linking)
VI  - 35
IP  - 10
DP  - 2021 Oct
TI  - Paclobutrazol exposure induces apoptosis and impairs autophagy in hepatocytes via 
      the AMPK/mTOR signaling pathway.
PG  - e22874
LID - 10.1002/jbt.22874 [doi]
AB  - 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 muM) 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.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Luo, Yun
AU  - Luo Y
AD  - Institute of Medicinal Plant Development, Peking Union Medical College and 
      Chinese Academy of Medical Sciences, Beijing, China.
AD  - Key Laboratory of Bioactive Substances and Resources Utilization of Chinese 
      Herbal Medicine, Ministry of Education, Beijing, China.
AD  - Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese 
      Medicine (Natural Medicine) and Translational Medicine, Beijing, China.
FAU - Lu, Shan
AU  - Lu S
AD  - Institute of Medicinal Plant Development, Peking Union Medical College and 
      Chinese Academy of Medical Sciences, Beijing, China.
AD  - Key Laboratory of Bioactive Substances and Resources Utilization of Chinese 
      Herbal Medicine, Ministry of Education, Beijing, China.
AD  - Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese 
      Medicine (Natural Medicine) and Translational Medicine, Beijing, China.
FAU - Sun, Xiao
AU  - Sun X
AD  - Institute of Medicinal Plant Development, Peking Union Medical College and 
      Chinese Academy of Medical Sciences, Beijing, China.
AD  - Key Laboratory of Bioactive Substances and Resources Utilization of Chinese 
      Herbal Medicine, Ministry of Education, Beijing, China.
AD  - Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese 
      Medicine (Natural Medicine) and Translational Medicine, Beijing, China.
FAU - Gao, Ye
AU  - Gao Y
AD  - Institute of Medicinal Plant Development, Peking Union Medical College and 
      Chinese Academy of Medical Sciences, Beijing, China.
FAU - Sun, Guibo
AU  - Sun G
AD  - Institute of Medicinal Plant Development, Peking Union Medical College and 
      Chinese Academy of Medical Sciences, Beijing, China.
AD  - Key Laboratory of Bioactive Substances and Resources Utilization of Chinese 
      Herbal Medicine, Ministry of Education, Beijing, China.
AD  - Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese 
      Medicine (Natural Medicine) and Translational Medicine, Beijing, China.
FAU - Yang, Meihua
AU  - Yang M
AD  - Institute of Medicinal Plant Development, Peking Union Medical College and 
      Chinese Academy of Medical Sciences, Beijing, China.
AD  - Key Laboratory of Bioactive Substances and Resources Utilization of Chinese 
      Herbal Medicine, Ministry of Education, Beijing, China.
FAU - Sun, Xiaobo
AU  - Sun X
AUID- ORCID: 0000-0003-4745-1709
AD  - Institute of Medicinal Plant Development, Peking Union Medical College and 
      Chinese Academy of Medical Sciences, Beijing, China.
AD  - Key Laboratory of Bioactive Substances and Resources Utilization of Chinese 
      Herbal Medicine, Ministry of Education, Beijing, China.
AD  - Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese 
      Medicine (Natural Medicine) and Translational Medicine, Beijing, China.
LA  - eng
GR  - 2017-I2M-1-013/CAMS Innovation Fund for Medical Sciences (CIFMS)/
PT  - Journal Article
DEP - 20210805
PL  - United States
TA  - J Biochem Mol Toxicol
JT  - Journal of biochemical and molecular toxicology
JID - 9717231
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Phytochemicals)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Triazoles)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 6PLV42R3ZA (paclobutrazol)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Catalase/metabolism
MH  - Cell Line, Transformed
MH  - Cell Survival/drug effects
MH  - Drugs, Chinese Herbal/*adverse effects
MH  - Hepatocytes/drug effects/*metabolism
MH  - Humans
MH  - Malondialdehyde/metabolism
MH  - Ophiopogon/chemistry
MH  - Oxidative Stress/drug effects
MH  - Phytochemicals/*adverse effects
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects
MH  - Superoxide Dismutase/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Triazoles/*adverse effects
OTO - NOTNLM
OT  - AKT/mTOR signaling pathway
OT  - apoptosis
OT  - autophagy
OT  - hepatocyte
OT  - paclobutrazol
EDAT- 2021/08/06 06:00
MHDA- 2022/02/04 06:00
CRDT- 2021/08/05 08:54
PHST- 2021/05/18 00:00 [revised]
PHST- 2020/12/02 00:00 [received]
PHST- 2021/07/24 00:00 [accepted]
PHST- 2021/08/06 06:00 [pubmed]
PHST- 2022/02/04 06:00 [medline]
PHST- 2021/08/05 08:54 [entrez]
AID - 10.1002/jbt.22874 [doi]
PST - ppublish
SO  - J Biochem Mol Toxicol. 2021 Oct;35(10):e22874. doi: 10.1002/jbt.22874. Epub 2021 
      Aug 5.