RRC ID 60795
Author Ku CC, Wuputra K, Kato K, Lin WH, Pan JB, Tsai SC, Kuo CJ, Lee KH, Lee YL, Lin YC, Saito S, Noguchi M, Nakamura Y, Miyoshi H, Eckner R, Nagata K, Wu DC, Lin CS, Yokoyama KK.
Title Jdp2-deficient granule cell progenitors in the cerebellum are resistant to ROS-mediated apoptosis through xCT/Slc7a11 activation.
Journal Sci Rep
Abstract 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 glutamate‒cystine 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 (p21Cip1) 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 p21Cip1 regulates the GCP apoptosis, which is one of critical events for normal development of the cerebellum.
Volume 10(1)
Pages 4933
Published 2020-3-18
DOI 10.1038/s41598-020-61692-x
PII 10.1038/s41598-020-61692-x
PMID 32188872
PMC PMC7080836
IF 3.998
Times Cited 2
DNA material pCMV_S-FLAG (RDB05956)