Exacerbated vulnerability to oxidative stress in astrocytic C6 glioma cells with stable overexpression of the glutamine transporter slc38a1

Masato Ogura, Takeshi Takarada, Noritaka Nakamichi, Hirofumi Kawagoe, Aya Sako, Ryota Nakazato, Yukio Yoneda

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 (H2O 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 H2O2, whereas H2O2 was significantly more effective in increasing NO2 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.

Original languageEnglish
Pages (from-to)504-511
Number of pages8
JournalNeurochemistry International
Volume58
Issue number4
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

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Keywords

  • Astrocytes
  • Glutamine transporter
  • HO-1
  • Oxidative stress
  • Reactive oxygen species
  • slc38a1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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