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N-acetyl-cysteine blunts 6-hydroxydopamine- and L-buthionine-sulfoximine-induced apoptosis in human mesenchymal stromal cells
- Source :
- Molecular biology reports. 46(4)
- Publication Year :
- 2019
-
Abstract
- Parkinson disease (PD) is characterized by the loss of dopaminergic (DAergic) neurons linked to environmental toxicants that cause oxidative stress (OS). The aim of this investigation was to establish the molecular response of human mesenchymal stroma cells (MSCs) depleted of glutathione (GSH) by the specific inhibitor l-buthionine-sulfoximine (BSO) to 6-hydroxydopamine (6-OHDA) and/or N-acetylcysteine (NAC) co-treatment. We found that treatment with BSO (10 mM) plus 6-OHDA (200 μM) induced apoptosis in MSCs through an oxidative stress (OS) mechanism involving H2O2, reflected by the detection of dichlorofluorescein-positive (DCF+) cells and oxidation of DJ-1 Cys106-SH into DJ-1 Cys106-SO3; an almost complete reduction in glutathione peroxidase 1 (GPX1) expression; activation of the transcription factor c-JUN, the pro-apoptotic protein BAX and BH-3-only protein PUMA; loss of mitochondrial membrane potential (∆Ψm); activation of the protease caspase-3 (CASP3) and apoptosis-inducing factor (AIF); chromatin condensation; and DNA fragmentation. Strikingly, co-treatment of MSCs with NAC (5 mM) and BSO + 6-OHDA significantly reduced the expression of OS and cell death markers but were unable to restore the expression of GPX1 compared to the expression in untreated or treated cells with NAC only. These findings highlighted the importance of the maintenance of the GSH-dependent (e.g., GPX1, GSH synthesis) and -independent (e.g., ROS scavenger molecules and thiol reducing activity) antioxidant systems (e.g., NAC) in the protection of MSCs from detrimental stress stimuli, thereby increasing the survival of stromal cells.
- Subjects :
- 0301 basic medicine
GPX1
Programmed cell death
Stromal cell
Apoptosis
medicine.disease_cause
Antioxidants
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Glutathione Peroxidase GPX1
Genetics
medicine
Humans
Oxidopamine
Molecular Biology
Buthionine Sulfoximine
Membrane Potential, Mitochondrial
Hydroxydopamine
Glutathione Peroxidase
Cell Death
Mesenchymal stem cell
Mesenchymal Stem Cells
General Medicine
Glutathione
Hydrogen Peroxide
Cell biology
Acetylcysteine
Oxidative Stress
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Reactive Oxygen Species
Oxidation-Reduction
Oxidative stress
Subjects
Details
- ISSN :
- 15734978
- Volume :
- 46
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular biology reports
- Accession number :
- edsair.doi.dedup.....5698432b143301c4014fda68532732b9