Down-regulation of ARC contributes to vulnerability of hippocampal neurons to ischemia/hypoxia.
ARC is a caspase recruitment domain-containing molecule that plays an important role in the regulation of apoptosis. We examined ARC expression during neuronal cell death following ischemic injury in vivo and in vitro. After exposure to transient global ischemic conditions, the expression of ARC was substantially reduced in the CA1 region of hippocampus in a time-dependent manner with concomitant increase of TUNEL-positive cells. Quantitative analysis using Western blotting exhibited that most of ARC protein disappeared in the cultured hippocampal neurons exposed to hypoxia for 12 h and showing 60% cell viability. Forced expression of ARC in the primary cultures of hippocampal neurons or B103 neuronal cells significantly reduced hypoxia-induced cell death. Further, the C-terminal P/E rich region of ARC was effective to attenuate hypoxic insults. These results suggest that down-regulation of ARC expression in hippocampal neurons may contribute to neuronal death induced by ischemia/hypoxia.
Hong
Yeon-Mi
YM
Department of Life Science, Kwangju Institute of Science and Technology, Buk-gu, 500-712, Kwangju, South Korea.
Jo
Dong-Gyu
DG
Lee
Joo-Yong
JY
Chang
Jae-Woong
JW
Nam
Jung-Hyun
JH
Noh
Jee Yeon
JY
Koh
Jae-Young
JY
Jung
Yong-Keun
YK
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death; D015687:Cell Hypoxia; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D006624:Hippocampus / Q000166:cytology / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology*; D007700:Kinetics; D009124:Muscle Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats
D051017:Apoptosis Regulatory Proteins; D009124:Muscle Proteins; C491788:Nol3 protein, rat