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)