RRC ID |
18186
|
著者 |
Ogura M, Takarada T, Nakamichi N, Kawagoe H, Sako A, Nakazato R, Yoneda Y.
|
タイトル |
Exacerbated vulnerability to oxidative stress in astrocytic C6 glioma cells with stable overexpression of the glutamine transporter slc38a1.
|
ジャーナル |
Neurochem Int
|
Abstract |
We have previously demonstrated the functional expression of glutamine (Gln) transporter (GlnT) believed to predominate in neurons for the neurotransmitter glutamate pool by rat neocortical astrocytes devoid of neuronal marker expression, with exacerbated vulnerability to oxidative stress after transient overexpression. To evaluate molecular mechanisms underlying the exacerbation, we established stable GlnT transfectants in rat astrocytic C6 glioma cells. In two different clones of stable transfectants with increased intracellular Gln levels, exposure to hydrogen peroxide (H(2)O(2)) and A23187, but not to tunicamycin or 2,4-dinitrophenol, led to significant exacerbation of the cytotoxicity compared to cells with empty vector (EV). Stable GlnT overexpression led to a significant increase in heme oxygenase-1 protein levels in a manner sensitive to H(2)O(2), whereas H(2)O(2) was significantly more effective in increasing NO(2) accumulation and reactive oxygen species (ROS) generation in stable GlnT transfectants than in EV cells. Moreover, exposure to A23187 led to a more effective increase in the generation of ROS in stable GlnT transfectants than in stable EV transfectants. These results suggest that GlnT may play a role in the mechanisms underlying the determination of cellular viability in astrocytes through modulation of intracellular ROS generation.
|
巻・号 |
58(4)
|
ページ |
504-11
|
公開日 |
2011-3-1
|
DOI |
10.1016/j.neuint.2011.01.007
|
PII |
S0197-0186(11)00009-X
|
PMID |
21219957
|
MeSH |
Amino Acid Transport System A / genetics
Amino Acid Transport System A / metabolism*
Animals
Blotting, Northern
Blotting, Western
Brain Neoplasms / metabolism*
Cell Line, Tumor
Chromatography, High Pressure Liquid
Glioma / metabolism*
Hydrogen Peroxide / pharmacology
Nitric Oxide / biosynthesis
Oxidative Stress*
Rats
Rats, Wistar
Reactive Oxygen Species / metabolism
|
IF |
3.881
|
引用数 |
16
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
NEUROSCIENCES
|
リソース情報 |
ヒト・動物細胞 |
C6(RCB2854) |