Ape1/Ref-1 Stimulates GDNF/GFR alpha1-mediated Downstream Signaling and Neuroblastoma Proliferation.
10.4196/kjpp.2009.13.5.349
- Author:
Mi Young KANG
1
;
Kweon Young KIM
;
Young YOON
;
Yoonsung KANG
;
Hong Beum KIM
;
Cha Kyung YOUN
;
Dong Hui KIM
;
Mi Hwa KIM
Author Information
1. Department of Pharmacology, DNA Repair Center, Chosun University School of Medicine, Gwangju 501-759, Korea. 9766m@hanmail.net
- Publication Type:Original Article
- Keywords:
Ape1/Ref-1;
GFR alpha1;
GDNF;
Lipid raft;
Neuronal proliferation;
Signal pathway
- MeSH:
Animals;
Cell Proliferation;
Down-Regulation;
Glial Cell Line-Derived Neurotrophic Factor;
Mice;
Neuroblastoma;
Neuroglia;
Neurons;
RNA;
RNA, Small Interfering;
Signal Transduction
- From:The Korean Journal of Physiology and Pharmacology
2009;13(5):349-356
- CountryRepublic of Korea
- Language:English
-
Abstract:
We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor alpha1 (GFR alpha1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFRalpha1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR alpha1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFRalpha1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR alpha1-specific RNA experiments demonstrated that the downregulation of GFR alpha1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC gamma-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR alpha signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.
