Abstract
Preconditioning (PC) is subtoxic insult that induces neuronal ischemic tolerance to subsequent, prolonged, lethal ischemia. Previous studies, including by us, have revealed that the production of nitric oxide (NO) during PC is increased, and this enhanced NO production is crucial to the development of PC-induced neuronal ischemic tolerance in neuron/astrocyte co-cultures. In addition, we have recently revealed that astrocytic glutamate transporter GLT-1 is transiently down-regulated after PC treatment, and the ischemia-induced rise of extracellular glutamate via reversed uptake of GLT-1 is significantly suppressed for the protection of neurons. This study aims at elucidating whether the increase of NO synthesis during PC is crucial for the PC-induced down-regulation of GLT-1. The present Western blotting analysis demonstrated that the PC-induced down-regulation of GLT-1 24 h after the PC insult was significantly suppressed by treatment with NG-methyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase (NOS), during the PC insult. In contrast, treatment of co-cultures with S-nitroso-N-acetyl-DL-penicillamine (SNAP), a donor of NO, significantly down-regulated the expression of astrocytic GLT-1. In conclusion, the present study suggested that NO produced during PC was critical to the PC-induced down-regulation of GLT-1 for the PC-induced neuronal ischemic tolerance [Jpn J Physiol 55 Suppl:S233 (2005)]
