Nitric oxide produced during sublethal ischemia is crucial for the preconditioning-induced down-regulation of glutamate transporter GLT-1 in neuron/astrocyte co-cultures.
In the brain, prior sublethal ischemia (preconditioning, PC) produces tolerance of neurons to subsequent lethal ischemia. This study aims at elucidating whether and how nitric oxide (NO) produced during PC is involved in the PC-induced ischemic tolerance of neurons in neuron/astrocyte co-cultures. The rise in the extracellular concentration of glutamate during ischemia caused by the reversed uptake of glutamate (Glu) by the astrocytic Glu transporter GLT-1 was markedly suppressed by the prior PC treatment, but the suppression was reversed by treatment with an inhibitor of nitric oxide synthase (NOS) during PC. Immunocytochemical and Western blot analyses demonstrated that the expression of GLT-1 was down-regulated after the PC insult, and this down-regulation was also antagonized by treatment with NOS inhibitors during PC. Here we show that nNOS-derived NO produced during PC was crucial for the down-regulation of astrocytic GLT-1, and this down-regulation coincided with an increased survival rate of neurons.
Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814, Japan.
Takeshi
T
Yamada
Koichi
K
Kawahara
Tatsuro
T
Kosugi
Motoki
M
Tanaka
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D004789:Enzyme Activation; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D019194:Ischemic Preconditioning; D007527:Isoenzymes / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats
D027342:Excitatory Amino Acid Transporter 2; D007527:Isoenzymes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase