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The Pharmaceutical Society of Korea (대한약학회)
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Mitogen-Activated Protein Kinases (MAPKs) Mediate SIN-1/ Glucose Deprivation-Induced Death in Rat Primary Astrocytes

  • Yoo Byoung-Kwon (Department of Pharmacology, College of Pharmacy, Seoul National University) ;
  • Choi Ji-Woong (Department of Pharmacology, College of Pharmacy, Seoul National University) ;
  • Choi Min-Sik (Department of Pharmacology, College of Pharmacy, Seoul National University) ;
  • Ryu Mi-Kyoung (Department of Pharmacology, College of Pharmacy, Seoul National University) ;
  • Park Gyu-Hwan (Department of Pharmacology, College of Pharmacy, Seoul National University) ;
  • Jeon Mi-Jin (Department of Pharmacology, College of Pharmacy, Seoul National University) ;
  • Ko Kwang-Ho (Department of Pharmacology, College of Pharmacy, Seoul National University)
  • Published : 2005.08.01
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Abstract

Peroxynitrite is a potent neurotoxic molecule produced from a reaction between NO and super-oxide 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 $50 {\mu}M$ 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 $20{\mu}M$ 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.

Keywords

References

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