Stem cells alleviate OGD/R mediated stress response in PC12 cells following a co-culture : modulation of the apoptotic cascade through BDNF-TrkB signaling
© 2023. The Author(s), under exclusive licence to Cell Stress Society International..
Apoptosis mediated by endoplasmic reticulum (ER) stress plays a crucial role in several neurovascular disorders, including ischemia/reperfusion injury (I/R injury). Previous in vitro and in vivo studies have suggested that following I/R injury, ER stress is vital for mediating CCAT-enhancer-binding protein homologous protein (CHOP) and caspase-12-dependent apoptosis. However, its modulation in the presence of stem cells and the underlying mechanism of cytoprotection remains elusive. In vivo studies from our lab have reported that post-stroke endovascular administration of stem cells renders neuroprotection and regulates apoptosis mediated by ER stress. In the current study, a more robust in vitro validation has been undertaken to decipher the mechanism of stem cell-mediated cytoprotection. Results from our study have shown that oxygen-glucose deprivation/reoxygenation (OGD/R) potentiated ER stress and apoptosis in the pheochromocytoma 12 (PC12) cell line as evident by the increase of protein kinase R (PKR)-like ER kinase (p-PERK), p-Eukaryotic initiation factor 2α subunit (EIF2α), activation transcription factor 4 (ATF4), CHOP, and caspase 12 expressions. Following the co-culture of PC12 cells with MSCs, ER stress was significantly reduced, possibly via modulating the brain-derived neurotrophic factor (BDNF) signaling. Furthermore, inhibition of BDNF by inhibitor K252a abolished the protective effects of BDNF secreted by MSCs following OGD/R. Our study suggests that inhibition of ER stress-associated apoptotic pathway with MSCs co-culture following OGD/R may help to alleviate cellular injury and further substantiate the use of stem cells as a therapeutic modality toward neuroprotection following hypoxic injury or stroke in clinical settings.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Cell stress & chaperones - 28(2023), 6 vom: 16. Nov., Seite 1041-1051 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kaur, Harpreet [VerfasserIn] |
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| Links: |
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| Themen: |
Apoptosis |
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| Anmerkungen: |
Date Completed 16.02.2024 Date Revised 06.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12192-022-01319-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Apoptosis mediated by endoplasmic reticulum (ER) stress plays a crucial role in several neurovascular disorders, including ischemia/reperfusion injury (I/R injury). Previous in vitro and in vivo studies have suggested that following I/R injury, ER stress is vital for mediating CCAT-enhancer-binding protein homologous protein (CHOP) and caspase-12-dependent apoptosis. However, its modulation in the presence of stem cells and the underlying mechanism of cytoprotection remains elusive. In vivo studies from our lab have reported that post-stroke endovascular administration of stem cells renders neuroprotection and regulates apoptosis mediated by ER stress. In the current study, a more robust in vitro validation has been undertaken to decipher the mechanism of stem cell-mediated cytoprotection. Results from our study have shown that oxygen-glucose deprivation/reoxygenation (OGD/R) potentiated ER stress and apoptosis in the pheochromocytoma 12 (PC12) cell line as evident by the increase of protein kinase R (PKR)-like ER kinase (p-PERK), p-Eukaryotic initiation factor 2α subunit (EIF2α), activation transcription factor 4 (ATF4), CHOP, and caspase 12 expressions. Following the co-culture of PC12 cells with MSCs, ER stress was significantly reduced, possibly via modulating the brain-derived neurotrophic factor (BDNF) signaling. Furthermore, inhibition of BDNF by inhibitor K252a abolished the protective effects of BDNF secreted by MSCs following OGD/R. Our study suggests that inhibition of ER stress-associated apoptotic pathway with MSCs co-culture following OGD/R may help to alleviate cellular injury and further substantiate the use of stem cells as a therapeutic modality toward neuroprotection following hypoxic injury or stroke in clinical settings | ||
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