DARPP-32의 인간 신경줄기세포 증식과 생존에서의 역할 규명

Abstract

To investigate the role of dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP-32), also known as protein phosphatase 1 regulatory subunit 1B (PPP1R1B), in cell proliferation and survival of human neural stem cells (hiNSCs) induced from human adipose-derived stem cells, DARPP-32 expression was knocked down by a lentiviral vector. Cell proliferation was relatively slower and doubling time was longer in the DARPP-32-knockdown hNSCs than in the scrambled control. Oxidative stress testing showed that DARPP-32 knockdown caused more cell death in hiNSCs after hydrogen peroxide (H2O2) treatment than in the scrambled control. The expressions of CTNNB1, CXCR4, and VCAM-1, which are related to cell proliferation, were lower in the DARPP-32-knockdown hiNSCs than in the scrambled control. In addition, DARPP-32 knockdown decreased the expression of Bcl-2 and increased the expression of Bax in response to H2O2 treatment. We also confirmed reduced expression of phosphorylated Akt (p-AKT) in DARPP-32-knockdown hiNSCs. In conclusion, these findings demonstrate the mechanisms by which DARPP-32 positively affects cell proliferation and survival in hiNSCs.