Emodin Ameliorates High Glucose-Induced Podocyte Apoptosis via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway.
10.1007/s11655-022-3540-9
- Author:
Hong LIU
1
;
Wei-Dong CHEN
1
;
Yang-Lin HU
1
;
Wen-Qiang YANG
2
;
Tao-Tao HU
1
;
Huan-Lan WANG
1
;
Yan-Min ZHANG
3
Author Information
1. Department of Nephrology, Wuhan No. 1 Hospital, Wuhan, 430022, China.
2. Department of Central Laboratory, Wuhan No. 1 Hospital, Wuhan, 430022, China.
3. Department of Nephrology, Wuhan No. 1 Hospital, Wuhan, 430022, China. hydzym@sina.com.
- Publication Type:Journal Article
- Keywords:
adenosine-monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathways;
autophagy;
diabetic nephropathy;
emodin;
podocyte apoptosis
- MeSH:
Emodin/pharmacology*;
AMP-Activated Protein Kinases/metabolism*;
Podocytes;
Caspase 3/metabolism*;
TOR Serine-Threonine Kinases/metabolism*;
Signal Transduction;
Apoptosis;
Sirolimus/pharmacology*;
Glucose/metabolism*;
Autophagy
- From:
Chinese journal of integrative medicine
2023;29(9):801-808
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the effect of emodin on high glucose (HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to induction of adenosine-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)-mediated autophagy in podocytes (MPC5 cells) in vitro.
METHODS:MPC5 cells were treated with different concentrations of HG (2.5, 5, 10, 20, 40, 80 and 160 mmol/L), emodin (2, 4, 8 µ mol/L), or HG (40 mmol/L) and emodin (4 µ mol/L) with or without rapamycin (Rap, 100 nmol/L) and compound C (10 µ mol/L). The viability and apoptosis of MPC5 cells were detected using cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy marker light chain 3 (LC3) I/II, and AMPK/mTOR signaling pathway-related proteins were determined by Western blot. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.
RESULTS:HG at 20, 40, 80 and 160 mmol/L dose-dependently induced cell apoptosis in MPC5 cells, whereas emodin (4 µ mol/L) significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage (P<0.01). Emodin (4 µ mol/L) significantly increased LC3-II protein expression levels and induced RFP-LC3-containing punctate structures in MPC5 cells (P<0.01). Furthermore, the protective effects of emodin were mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 µ mol/L) reversed emodin-induced autophagy activation.
CONCLUSION:Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway, which might provide a potential therapeutic option for diabetic nephropathy.
