Rg1 protects H9C2 cells from high glucose-/palmitate-induced injury via activation of AKT/GSK-3β/Nrf2 pathway.
Antioxidants
/ metabolism
Apoptosis
/ drug effects
Cytoprotection
/ drug effects
Drug Tapering
Ginsenosides
/ pharmacology
Glucose
/ adverse effects
Glycogen Synthase Kinase 3 beta
/ metabolism
Models, Biological
NF-E2-Related Factor 2
/ metabolism
Palmitates
/ adverse effects
Protective Agents
/ pharmacology
Proto-Oncogene Proteins c-akt
/ metabolism
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ drug effects
AKT/GSK-3β/Nrf2
H9C2 cells
diabetes
ginsenoside Rg1
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
09
03
2020
revised:
06
05
2020
accepted:
24
05
2020
pubmed:
18
6
2020
medline:
11
5
2021
entrez:
18
6
2020
Statut:
ppublish
Résumé
Our previous studies have assessed ginsenoside Rg1 (Rg1)-mediated protection in a type 1 diabetes rat model. To uncover the mechanism through which Rg1 protects against cardiac injury induced by diabetes, we mimicked diabetic conditions by culturing H9C2 cells in high glucose/palmitate. Rg1 had no toxic effect, and it alleviated the high glucose/palmitate damage in a dose-dependent manner, as indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release to the culture medium. Rg1 prevented high glucose/palmitate-induced cell apoptosis, assessed using cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling staining. Rg1 also reduced high glucose-/palmitate-induced reactive oxygen species formation and increased intracellular antioxidant enzyme activity. We found that Rg1 activates protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3β) pathway and antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, indicated by increased phosphorylation of AKT and GSK-3β, and nuclear translocation of Nrf2. We used phosphatidylinositol-3-kinase inhibitor Ly294002 to block the activation of the AKT/GSK-3β pathway and found that it partially reversed the protection by Rg1 and decreased Nrf2 pathway activation. The results suggest that Rg1 exerts a protective effect against high glucose and palmitate damage that is partially AKT/GSK-3β/Nrf2-mediated. Further studies are required to validate these findings using primary cardiomyocytes and animal models of diabetes.
Identifiants
pubmed: 32548942
doi: 10.1111/jcmm.15486
pmc: PMC7348154
doi:
Substances chimiques
Antioxidants
0
Ginsenosides
0
NF-E2-Related Factor 2
0
Palmitates
0
Protective Agents
0
Reactive Oxygen Species
0
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Glucose
IY9XDZ35W2
ginsenoside Rg1
PJ788634QY
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8194-8205Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
Circulation. 2006 Jan 31;113(4):544-54
pubmed: 16432057
J Cardiovasc Pharmacol. 2017 Sep;70(3):184-193
pubmed: 28678055
Cell Death Dis. 2018 May 22;9(6):598
pubmed: 29789524
BMC Complement Altern Med. 2016 May 26;16:146
pubmed: 27228978
J Cardiovasc Pharmacol. 2017 Dec;70(6):422-429
pubmed: 28654509
J Cell Biochem. 2012 Jun;113(6):1987-97
pubmed: 22253095
J Cell Mol Med. 2016 Apr;20(4):623-31
pubmed: 26869403
Diabetes. 2017 Feb;66(2):529-542
pubmed: 27903744
Korean J Intern Med. 2017 May;32(3):404-421
pubmed: 28415836
Oxid Med Cell Longev. 2016;2016:4690857
pubmed: 27313828
Am J Transl Res. 2018 Sep 15;10(9):2810-2821
pubmed: 30323868
Diabetes. 2007 Jul;56(7):1834-41
pubmed: 17473225
Diabetologia. 2014 Apr;57(4):660-71
pubmed: 24477973
Diabetes Metab J. 2014 Oct;38(5):337-45
pubmed: 25349820
Diabetes Metab Syndr Obes. 2019 Jul 10;12:1091-1103
pubmed: 31372019
J Cell Mol Med. 2020 Jul;24(14):8194-8205
pubmed: 32548942
Oxid Med Cell Longev. 2019 Nov 25;2019:2053149
pubmed: 31885775
Biochim Biophys Acta. 2012 Apr;1820(4):453-60
pubmed: 22178929
Theranostics. 2017 Sep 20;7(16):4001-4012
pubmed: 29109794
Int J Mol Sci. 2018 Nov 20;19(11):
pubmed: 30463294
Mol Med Rep. 2019 May;19(5):3633-3641
pubmed: 30864725
Circulation. 2016 Jun 14;133(24):2459-502
pubmed: 27297342
Circ Res. 2018 Feb 16;122(4):624-638
pubmed: 29449364
Diabetologia. 2018 Jan;61(1):21-28
pubmed: 28776083
Front Physiol. 2018 Feb 07;9:78
pubmed: 29467677
Redox Biol. 2018 Apr;14:609-617
pubmed: 29154192
Acta Pharmacol Sin. 2020 May;41(5):638-649
pubmed: 31768045
Front Immunol. 2018 Nov 05;9:2527
pubmed: 30455692
Cells. 2018 Dec 12;7(12):
pubmed: 30545139
Acta Cir Bras. 2019 Sep 12;34(7):e201900708
pubmed: 31531541
Redox Biol. 2018 May;15:405-417
pubmed: 29353218
Cell Stress Chaperones. 2019 Mar;24(2):441-452
pubmed: 30815818
Cell. 2017 Aug 10;170(4):605-635
pubmed: 28802037
Braz J Med Biol Res. 2017 Dec 11;51(2):e6611
pubmed: 29267498
PLoS One. 2015 Jun 15;10(6):e0129676
pubmed: 26075390
Diabetologia. 2012 Dec;55(12):3369-81
pubmed: 23001375
Physiol Genomics. 2018 Feb 1;50(2):77-97
pubmed: 29187515
Mol Cell Biochem. 2014 Jul;392(1-2):249-57
pubmed: 24671491
Int Immunopharmacol. 2020 Feb;79:106108
pubmed: 31881376
Free Radic Biol Med. 2016 Dec;101:401-412
pubmed: 27836781
J Cell Mol Med. 2016 Jul;20(7):1352-66
pubmed: 26991817
Cell Death Dis. 2018 Oct 23;9(11):1087
pubmed: 30352996
J Zhejiang Univ Sci B. 2015 May;16(5):344-54
pubmed: 25990051
J Virol. 2018 Nov 12;92(23):
pubmed: 30209179