Possible involvement of extracellular ATP-P2Y purinoceptor signaling in ischemia-induced tolerance of astrocytes in culture.
Extracellular adenosine 5'-triphosphate (ATP) activates specific G protein-coupled purinoceptors (P2Y), and ATP-P2Y signaling pathways induces intracellular Ca(2+) mobilization resulting in changes in the gene expression of a variety of proteins in astrocytes. This study investigated whether the exposure of cultured astrocytes to sublethal ischemia produced resistance to subsequent lethal ischemic stress, and if so, whether the extracellular ATP-P2Y signaling pathways were responsible for the tolerance. Ischemia-like insults, sublethal oxygen-glucose deprivation (sOGD), produced tolerance to subsequent lethal OGD stress in cultured astrocytes. Early during reperfusion after sOGD, the amount of extracellular ATP and the expression of both P2Y(1) and P2Y(2) receptors were increased, leading to enhanced activation of the extracellular ATP-P2Y signaling pathways. The occurrence of intracellular spontaneous Ca(2+) oscillations was also increased. In addition, sOGD treatment enhanced the expression of the phosphorylated form of extracellular signal-regulated protein kinases 1 and 2 (p-ERK 1/2), and treatment with an inhibitor of ERK significantly attenuated the sOGD-induced ischemic tolerance of astrocytes.
Iwabuchi
Sadahiro
S
Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan.
Kawahara
Koichi
K
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002545:Brain Ischemia / Q000503:physiopathology*; D002470:Cell Survival; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose; D010100:Oxygen