| First Author | Ku CC | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 4933 |
| PubMed ID | 32188872 | Mgi Jnum | J:303363 |
| Mgi Id | MGI:6512114 | Doi | 10.1038/s41598-020-61692-x |
| Citation | Ku CC, et al. (2020) Jdp2-deficient granule cell progenitors in the cerebellum are resistant to ROS-mediated apoptosis through xCT/Slc7a11 activation. Sci Rep 10(1):4933 |
| abstractText | The Jun dimerization protein 2 (Jdp2) is expressed predominantly in granule cell progenitors (GCPs) in the cerebellum, as was shown in Jdp2-promoter-Cre transgenic mice. Cerebellum of Jdp2-knockout (KO) mice contains lower number of Atoh-1 positive GCPs than WT. Primary cultures of GCPs from Jdp2-KO mice at postnatal day 5 were more resistant to apoptosis than GCPs from wild-type mice. In Jdp2-KO GCPs, the levels of both the glutamatecystine exchanger Sc7a11 and glutathione were increased; by contrast, the activity of reactive oxygen species (ROS) was decreased; these changes confer resistance to ROS-mediated apoptosis. In the absence of Jdp2, a complex of the cyclin-dependent kinase inhibitor 1 (p21(Cip1)) and Nrf2 bound to antioxidant response elements of the Slc7a11 promoter and provide redox control to block ROS-mediated apoptosis. These findings suggest that an interplay between Jdp2, Nrf2, and p21(Cip1) regulates the GCP apoptosis, which is one of critical events for normal development of the cerebellum. |
