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Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism.
- Source :
-
Scientific reports [Sci Rep] 2020 Nov 26; Vol. 10 (1), pp. 20653. Date of Electronic Publication: 2020 Nov 26. - Publication Year :
- 2020
-
Abstract
- Human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are self-renewing human pluripotent stem cells (hPSCs) that can differentiate to a wide range of specialized cells. Notably, hPSCs enhance their undifferentiated state and self-renewal properties in hypoxia (5% O <subscript>2</subscript> ). Although thoroughly analyzed, hypoxia implication in hPSCs death is not fully determined. In order to evaluate the effect of chemically mimicked hypoxia on hPSCs cell survival, we analyzed changes in cell viability and several aspects of apoptosis triggered by CoCl <subscript>2</subscript> and dimethyloxalylglycine (DMOG). Mitochondrial function assays revealed a decrease in cell viability at 24 h post-treatments. Moreover, we detected chromatin condensation, DNA fragmentation and CASPASE-9 and 3 cleavages. In this context, we observed that P53, BNIP-3, and NOXA protein expression levels were significantly up-regulated at different time points upon chemical hypoxia induction. However, only siRNA-mediated downregulation of NOXA but not HIF-1α, HIF-2α, BNIP-3, and P53 did significantly affect the extent of cell death triggered by CoCl <subscript>2</subscript> and DMOG in hPSCs. In conclusion, chemically mimicked hypoxia induces hPSCs cell death by a NOXA-mediated HIF-1α and HIF-2α independent mechanism.
- Subjects :
- Caspase 3 genetics
Caspase 9 genetics
Cell Death genetics
Cell Survival genetics
DNA Fragmentation
Down-Regulation genetics
Humans
Membrane Proteins genetics
Mitochondria genetics
Signal Transduction genetics
Tumor Suppressor Protein p53 genetics
Up-Regulation genetics
Apoptosis genetics
Basic Helix-Loop-Helix Transcription Factors genetics
Cell Hypoxia genetics
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Pluripotent Stem Cells metabolism
Proto-Oncogene Proteins c-bcl-2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33244167
- Full Text :
- https://doi.org/10.1038/s41598-020-77792-7