Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway.
10.1007/s11655-022-3687-4
- Author:
Zhi-Ying ZHANG
1
;
Chao LIU
2
;
Peng-Xiang WANG
3
;
Yi-Wei HAN
2
;
Yi-Wen ZHANG
2
;
Mei-Li HAO
2
;
Zi-Xu SONG
2
;
Xiao-Ying ZHANG
4
Author Information
1. Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi Province, 712082, China.
2. School of Finance Economics, Xizang Minzu University, Xianyang, Shaanxi Province, 712082, China.
3. School of Information Engineering, Xizang Minzu University, Xianyang, Shaanxi Province, 712082, China.
4. Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi Province, 712082, China. zzy20210726@163.com.
- Publication Type:Journal Article
- Keywords:
PI3K/AKT/mTOR;
autophagy;
cell apoptosis;
circHIPK;
dihydromyricetin
- MeSH:
Proto-Oncogene Proteins c-akt/metabolism*;
Signal Transduction;
Phosphatidylinositol 3-Kinases/metabolism*;
TOR Serine-Threonine Kinases/metabolism*;
Apoptosis;
Autophagy
- From:
Chinese journal of integrative medicine
2023;29(5):434-440
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy.
METHODS:H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells.
RESULTS:Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05).
CONCLUSION:Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.
