Mitogen-activated protein kinases (MAPKs) mediate SIN-1/ glucose deprivation-induced death in rat primary astrocytes

oung Kwon Yoo; Ji Woong Choi; Min Sik Choi; Mi Kyoung Ryu; Gyu Hwan Park; Mi Jin Jeon; Kwang Ho Ko

doi:10.1007/BF02973881

Mitogen-activated protein kinases (MAPKs) mediate SIN-1/ glucose deprivation-induced death in rat primary astrocytes

Arch Pharm Res. 2005 Aug;28(8):942-7. doi: 10.1007/BF02973881.

Authors

oung Kwon Yoo¹, Ji Woong Choi, Min Sik Choi, Mi Kyoung Ryu, Gyu Hwan Park, Mi Jin Jeon, Kwang Ho Ko

Affiliation

¹ Department of Pharmacology, College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Korea.

PMID: 16178421
DOI: 10.1007/BF02973881

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 JNK1SAPK) signal pathway in the SIN-1/glucose deprivation-induced death of astrocytes was examined. A combined treatment with glucose deprivation and 50 microM 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 microM 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism
Animals
Anthracenes / pharmacology
Astrocytes / drug effects
Astrocytes / metabolism*
Astrocytes / pathology*
Brain Ischemia / metabolism
Brain Ischemia / prevention & control
Cell Culture Techniques
Cell Death / drug effects
Cells, Cultured
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology
Glucose / deficiency
Imidazoles / pharmacology
L-Lactate Dehydrogenase / analysis
L-Lactate Dehydrogenase / metabolism
MAP Kinase Signaling System / drug effects
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / metabolism*
Molsidomine / analogs & derivatives
Molsidomine / pharmacology
Nitric Oxide Donors / pharmacology
Peroxynitrous Acid* / biosynthesis
Pyridines / pharmacology
Rats
Rats, Sprague-Dawley
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Anthracenes
Enzyme Inhibitors
Flavonoids
Imidazoles
Nitric Oxide Donors
Pyridines
Peroxynitrous Acid
pyrazolanthrone
linsidomine
Adenosine Triphosphate
Molsidomine
L-Lactate Dehydrogenase
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Glucose
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one