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  • Jdp2-deficient granule cell progenitors in the cerebellum are resistant to ROS-mediated apoptosis through xCT/Slc7a11 activation.

Jdp2-deficient granule cell progenitors in the cerebellum are resistant to ROS-mediated apoptosis through xCT/Slc7a11 activation.

Scientific reports (2020-03-20)
Chia-Chen Ku, Kenly Wuputra, Kohsuke Kato, Wen-Hsin Lin, Jia-Bin Pan, Shih-Chieh Tsai, Che-Jung Kuo, Kan-Hung Lee, Yan-Liang Lee, Ying-Chu Lin, Shigeo Saito, Michiya Noguchi, Yukio Nakamura, Hiroyuki Miyoshi, Richard Eckner, Kyosuke Nagata, Deng-Chyang Wu, Chang-Shen Lin, Kazunari K Yokoyama
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Amyloid Protein Non-Aβ Component, ≥80% (HPLC)
Sigma-Aldrich
Anti-ATH 1 Antibody, Chemicon®, from rabbit