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Pretreatment With Argon Protects Human Cardiac Myocyte-Like Progenitor Cells from Oxygen Glucose Deprivation-Induced Cell Death by Activation of AKT and Differential Regulation of Mapkinases.
- Source :
-
Shock (Augusta, Ga.) [Shock] 2018 May; Vol. 49 (5), pp. 556-563. - Publication Year :
- 2018
-
Abstract
- Background: The noble gas argon induces cardioprotection in a rabbit model of myocardial ischemia and reperfusion. However, no studies in human primary cells or subjects have been performed so far. We used human cardiac myocyte-like progenitor cells (HCMs) to investigate the protective effect on the cellular level.<br />Methods: HCMs were pretreated with 30% or 50% argon before oxygen-glucose deprivation (OGD) and reperfusion. We evaluated apoptotic states by flow cytometry and the activation of mitogen-activated protein kinase (MAPKs) members extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), p38 MAPkinase, and protein kinase B (Akt) by Westernblot analysis and by activity assays of downstream transcription factors. Specific inhibitors were used to proof a significant participation of these pathways in the protection by argon. Beneficial effects were further assessed by TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay, lactate dehydrogenase (LDH), mitochondrial deoxyribonucleic acid (mtDNA), and cytokine release.<br />Results: Pretreatment with 30% or 50% argon for 90 min before OGD resulted in a significant protection of HCMs against apoptosis. This effect was reversed by the application of MAPK and Akt inhibitors during argon exposure. Argon 30% reduced the release of LDH by 33% and mtDNA by 45%. The release of interleukin 1β was reduced by 44% after OGD and more than 90% during reperfusion.<br />Conclusions: Pretreatment with argon protects HCMs from apoptosis under ischemic conditions via activation of Akt, Erk, and biphasic regulation of JNK. Argon gas is cheap and easily administrable, and might be a novel therapy to reduce myocardial ischemia-reperfusion injury.
- Subjects :
- Animals
Apoptosis drug effects
Extracellular Signal-Regulated MAP Kinases metabolism
Flow Cytometry
Humans
In Situ Nick-End Labeling
JNK Mitogen-Activated Protein Kinases metabolism
L-Lactate Dehydrogenase metabolism
Rabbits
Signal Transduction drug effects
Argon pharmacology
Myocytes, Cardiac cytology
Myocytes, Cardiac drug effects
Proto-Oncogene Proteins c-akt metabolism
Stem Cells cytology
Stem Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1540-0514
- Volume :
- 49
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 29658909
- Full Text :
- https://doi.org/10.1097/SHK.0000000000000998