Effects of sensitive to apoptosis gene protein on cell proliferation, neuroblast differentiation, and oxidative stress in the mouse dentate gyrus.
Sensitive to apoptosis gene (SAG) protein is a redox-inducible protein that protects cells against apoptosis induced by redox agents. In this study, we observed effects of SAG on cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus (DG) using Ki67 and doublecortin (DCX), respectively. For easy penetration into neurons, Tat-SAG expression vector was constructed by ligation with SAG and expression vector, Tat, in-frame with six histidine open-reading frames to generate the expression vector, and cloned into E. coli DH5α cells. One or 5 mg/kg Tat-SAG fusion protein (Tat-SAG) was intraperitoneally administered to mice once a day for 3 weeks. The administration of Tat-SAG significantly increased the number of 5-bromodeoxyuridine positive cells, Ki67 positive cells and DCX immunoreactive neuroblast in the mouse DG: Especially, in the 5 mg/kg Tat-SAG-treated mice, DCX positive neuroblasts showed a well-developed arborization of tertiary dendrites in the DG. On the other hand, we examined that the administration of Tat-SAG significantly reduced the DNA damage and lipid peroxidation judging from 8-hydroxy-2'-deoxyguanosine and 4-hydroxynonenal immunohistochemistry: The decrease was much more distinct in the 5 mg/kg Tat-SAG-treated mice than 1 mg/kg Tat-SAG-treated mice. This result suggests that SAG significantly increases cell proliferation, neuroblast differentiation and oxidative stress in normal states.
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
Dae Young
DY
Yoo
Bich Na
BN
Shin
In Hye
IH
Kim
Dae Won
DW
Kim
Ki-Yeon
KY
Yoo
Woosuk
W
Kim
Choong Hyun
CH
Lee
Jung Hoon
JH
Choi
Yeo Sung
YS
Yoon
Soo Young
SY
Choi
Moo-Ho
MH
Won
In Koo
IK
Hwang
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D004249:DNA Damage; D017931:DNA Primers; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D000089662:Doublecortin Protein; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology*; D018384:Oxidative Stress
D002352:Carrier Proteins; D017931:DNA Primers; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; C573100:SAG protein, mouse