Abstract
PARP-1 is a multifunctional enzyme that regulates DNA repair, chromatin remodeling, inflammation and cell survival. Our previous study revealed that PARP-1 is required for maintaining normal level of neural stem cell proliferation. In the present study, we present evidence indicating that PARP-1 regulates neural stem cell proliferation by upregulating the expression of platelet-derived growth factor receptor α (PDGFRα). PARP-1 knockout neural stem cells exhibited striking downregulation of PDGFRα expression. We found that PARP-1 promotes the transcription of PDGFRα independently of its enzymatic activity. Overexpression of PDGFRα in the PARP-1 knockout neural stem cells reversed the proliferation defect of the knockout cells. Conversely, knockdown or blocking antibody of PDGFRα suppressed the proliferation of neural stem cells. In addition, blockade of PDGFRα increased cell death rate. Consistent with the downregulation of PDGFRα in the absence of PARP-1, PDGF-AA promoted proliferation of wild-type neural stem cells but not that of PARP-1 knockout cells. These results suggest that PARP-1 can control the neural stem cell proliferation by regulating the expression of PDGFRα.
| Original language | English |
|---|---|
| Pages (from-to) | 986-992 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 526 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 11 Jun 2020 |
Bibliographical note
Publisher Copyright:© 2020 Elsevier Inc.
Keywords
- Neural stem cells
- Neurogenesis
- PARP-1
- PDGFRα