PMID- 37232350
OWN - NLM
STAT- MEDLINE
DCOM- 20230530
LR  - 20230607
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 52
IP  - 1
DP  - 2023 Jul
TI  - Ginsenoside Rg1 regulates autophagy and endoplasmic reticulum stress via the 
      AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate alcohol‑induced myocardial 
      injury.
LID - 56 [pii]
LID - 10.3892/ijmm.2023.5259 [doi]
AB  - It has been reported that ginsenoside Rg1 (G‑Rg1) can alleviate alcoholic liver 
      injury, cardiac hypertrophy and myocardial ischemia, as well as reperfusion 
      injury. Therefore, the present study aimed to investigate the role of G‑Rg1 in 
      alcohol‑induced myocardial injury, as well as to elucidate its underlying 
      mechanisms of action. For this purpose, H9c2 cells were stimulated with ethanol. 
      Subsequently, H9c2 cell viability and apoptosis were determined using a Cell 
      Counting Kit‑8 assay and flow cytometric analysis, respectively. The levels of 
      lactate dehydrogenase and caspase‑3 in the H9c2 cell culture supernatant were 
      detected using corresponding assay kits. In addition, the expression of green 
      fluorescent protein (GFP)‑light chain 3 (LC3) and that of C/EBP homologous 
      protein (CHOP) were evaluated using GFP‑LC3 assay and immunofluorescence 
      staining, respectively. The expression levels of apoptosis‑, autophagy‑, 
      endoplasmic reticulum stress (ERS)‑ and adenosine 5'‑monophosphate‑activated 
      protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway‑related 
      proteins were detected using western blot analysis. The results revealed that 
      treatment with G‑Rg1 enhanced the viability and suppressed the apoptosis of 
      ethanol‑stimulated H9c2 cells. G‑Rg1 also attenuated autophagy and ERS in 
      ethanol‑stimulated H9c2 cells. In addition, the levels of phosphorylated 
      (p)‑protein kinase R (PKR)‑like ER kinase (PERK), p‑eukaryotic translation 
      initiation factor 2a, activating transcription factor 4 (ATF4), CHOP, caspase‑12 
      and p‑AMPK were downregulated, while the p‑mTOR level was upregulated in 
      ethanol‑stimulated H9c2 cells treated with G‑Rg1. Furthermore, the co‑treatment 
      of G‑Rg1‑treated ethanol‑stimulated H9c2 cells with AICAR, an AMPK agonist, or 
      CCT020312, a PERK agonist, inhibited cell viability and promoted cell apoptosis, 
      autophagy and ERS. Overall, the results of the present study suggest that G‑Rg1 
      suppresses autophagy and ERS via inhibiting the AMPK/mTOR and PERK/ATF4/CHOP 
      pathways to alleviate ethanol‑induced H9c2 cell injury.
FAU - Tian, Ge
AU  - Tian G
AD  - Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical 
      University, Jinzhou, Liaoning 121000, P.R. China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Cardiology, The First Affiliated Hospital of China Medical 
      University, Shenyang, Liaoning 110001, P.R. China.
FAU - Zhou, Lina
AU  - Zhou L
AD  - Department of Geriatrics, The First Affiliated Hospital of Jinzhou Medical 
      University, Jinzhou, Liaoning 121000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20230526
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 3K9958V90M (Ethanol)
RN  - PJ788634QY (ginsenoside Rg1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Activating Transcription Factor 4/genetics/metabolism
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Apoptosis
MH  - Autophagy
MH  - Endoplasmic Reticulum Stress
MH  - Ethanol
MH  - *Heart Injuries
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Animals
MH  - Rats
PMC - PMC10241156
OTO - NOTNLM
OT  - adenosine 5'‑monophosphate‑activated protein kinase/mammalian target of rapamycin
OT  - autophagy
OT  - endoplasmic reticulum stress
OT  - ginsenoside Rg1
OT  - myocardial injury
OT  - protein kinase R (PKR)‑like ER kinase
COIS- The authors declare that they have no competing interests.
EDAT- 2023/05/26 13:09
MHDA- 2023/05/29 06:42
PMCR- 2023/05/23
CRDT- 2023/05/26 06:23
PHST- 2023/01/31 00:00 [received]
PHST- 2023/04/26 00:00 [accepted]
PHST- 2023/05/29 06:42 [medline]
PHST- 2023/05/26 13:09 [pubmed]
PHST- 2023/05/26 06:23 [entrez]
PHST- 2023/05/23 00:00 [pmc-release]
AID - 56 [pii]
AID - ijmm-52-1-05259 [pii]
AID - 10.3892/ijmm.2023.5259 [doi]
PST - ppublish
SO  - Int J Mol Med. 2023 Jul;52(1):56. doi: 10.3892/ijmm.2023.5259. Epub 2023 May 26.