Role of DARPP-32 in the Proliferation and Survival of Human Neural Stem Cells
이주희, 장미숙,
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이주희 ( Lee Ju-Hee ) - Seoul National University School of Dentistry Department of Oral Anatomy
장미숙 ( Chang Mi-Sook ) - Seoul National University School of Dentistry Department of Oral Anatomy
KMID : 0355820200410010097
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.
키워드
Cell proliferation; Cell survival; DARPP-32; Neural stem cell; Oxidative stress
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