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Glutathione Articles - Additional Usages
Hypoxia Increases The Dependence of Glioma Cells On
Glutathione
Toyin Adeyemi Ogunrinu and Harald Sontheimer
The Journal of Biological Chemistry 2010, 285, 37716-37724
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Glutathione (GSH) is an
essential antioxidant responsible for the maintenance of intracellular
redox-homeostasis. As tumors outgrow their blood supply and become
hypoxic, their redox-homeostasis is challenged by the production of
nitric oxide (NO) and reactive oxygen species (ROS). In gliomas, the
sustained import of L-cystine via the Lcystine/L-glutamate exchanger,
system xc-, is rate-limiting for the synthesis of GSH. We show that
hypoxia causes a significant increase in NO and ROS, yet without
affecting glioma cell growth. This is explained by a concomitant
increase in the utilization of GSH, which is
accompanied by an increase in the cell surface expression of xCT, the
catalytic subunit of system xc - and L-cystine uptake. Growth is
buthionine sulfoximine (BSO), an inhibitor of the enzyme required for
GSH synthesis or when cells are deprived of L-cystine. These findings
suggest that glioma cells show an increased requirement for GSH to
maintain growth under hypoxic conditions. Therefore, approaches that
limit GSH synthesis such as blocking system xc- may be considered as an
adjuvant to radiation or chemotherapy.
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