Mitogen-Activated Protein Kinases (MAPKs) Mediate SIN-1/Glucose Deprivation-Induced Death in Rat Primary Astrocytes

다국어 초록 (Multilingual Abstract)

Peroxynitrite is a potent neurotoxic molecule produced from a reaction between NO and superoxide
and induces NO-mediated inflammation under neuropathological conditions. Previously,
we reported that glucose deprivation induced ATP depletion and cell death in immunostimulated
astrocytes, which was mainly due to peroxynitrite. In this study, the role of MAPKs
(ERK1/2, p38MAPK, and JNK/SAPK) signal pathway in the SIN-1/glucose deprivation-induced
death of astrocytes was examined. A combined treatment with glucose deprivation and 50 μM
SIN-1, an endogenous peroxynitrite generator, rapidly and markedly increased the death in rat
primary astrocytes. Also, SIN-1/glucose deprivation resulted in the activation of MAPKs, which
was significantly blocked by the treatment with 20 μM MAPKs inhibitors (ERK1/2, PD98059;
p38MAPK, SB203580; JNK/SAPK, SP600125). Interestingly, SIN-1/glucose deprivation caused
the loss of intracellular ATP level, which was significantly reversed by MAPKs inhibitors. These
results suggest that the activation of MAPKs plays an important role in SIN-1/glucose deprivation-
induced cell death by regulating the intracellular ATP level.

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