Changes in the spontaneous calcium oscillations for the development of the preconditioning-induced ischemic tolerance in neuron/astrocyte co-culture.
Spontaneous Ca(2+) oscillations are believed to contribute to the regulation of gene expression. Here we investigated whether and how the dynamics of Ca(2+) oscillations changed after sublethal preconditioning (PC) for PC-induced ischemic tolerance in neuron/astrocyte co-cultures. The frequency of spontaneous Ca(2+) oscillations significantly decreased between 4 and 8 h after the end of PC in both neurons and astrocytes. Treatment with 2-APB, an inhibitor of IP3 receptors, decreased the oscillatory frequency, induced ischemic tolerance and a down-regulation of glutamate transporter GLT-1 contributing to the increase in the extracellular glutamate during ischemia. The expression of GLT-1 is known to be up-regulated by PACAP. Treatment with PACAP38 increased the oscillatory frequency, and antagonized both the PC-induced down-regulation of GLT-1 and ischemic tolerance. These results suggested that the PC suppressed the spontaneous Ca(2+) oscillations regulating the gene expressions of various proteins, especially of astrocytic GLT-1, for the development of the PC-induced ischemic tolerance.
Tanaka
Motoki
M
Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan.
Kawahara
Koichi
K
Kosugi
Tatsuro
T
Yamada
Takeshi
T
Mioka
Tetsuo
T
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002470:Cell Survival; D018920:Coculture Techniques; D005576:Colforsin / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000502:physiology; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000633:toxicity; D019194:Ischemic Preconditioning; D009474:Neurons / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D051381:Rats
D027342:Excitatory Amino Acid Transporter 2; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D005576:Colforsin; D018698:Glutamic Acid; D005947:Glucose; D002118:Calcium