Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
Ischemic stroke induces neuronal damage by various causes such as glutamate excitotoxicity, oxidative stress and trophic factor deficiency. A large amount of glutamate accumulated in an extracellular space is a major factor to lead intracellular Ca2+ elevation through the N-methyl-D-aspartate (NMDA) receptor after ischemia and then causes neuronal death. Although it has been identified that several proteolytic enzymes are activated by elevated intracellular Ca2+, roles of proteolytic enzymes associated with NMDA-induced neuronal death are not fully understood. Here, we determined whether inhibitions of proteolytic enzymes affected on NMDA-induced damage in rat cortical neurons. Primary cultures of rat cortical neurons were prepared from embryonic day 16 in this study. For cell viability assay, mitochondrial activity was measured by a XTT assay 24 hours after NMDA treatment with or without inhibitors of proteolytic enzymes. Inhibitions of matrix metalloproteinase, gamma-secretase, protein convertase subtilisin / kexin type 9 and furin were examined whether these proteases were associated with neuronal damage. Importantly, the furin inhibitor significantly protected cortical neurons from NMDA-induced neuronal death in a dose-dependent manner. Moreover, calpain activation induced by NMDA treatment was markedly blocked by the furin inhibitor without affecting intracellular Ca2+ concentration. Thus, the calpain activation would be involved in downstream of furin under NMDA-induced toxicity in rat cortical neurons. These results demonstrate that the furin inhibition may provide a therapeutic approach against ischemic neuronal damage.
