Calpain facilitates the neuron death induced by 3-nitropropionic acid and contributes to the necrotic morphology.

摘要: 3-Nitropropionic acid (3NP), an irreversible inhibitor of succinate dehydrogenase, has been used to model features neurodegenerative disorders including Huntington disease, as well acute neuronal insults such cerebral ischemia. 3NP induces rapid necrosis and delayed apoptosis in primary cultures rat hippocampal neurons. Low levels extracellular glutamate shift the cell death mechanism necrosis, whereas antagonism NMDA receptors results predominately apoptotic death. In present study, involvement cysteine proteases morphologic biochemical alterations accompanying 3NP-induced neuron was investigated. Immunoblots spectrin breakdown products indicated Ca(2+)-dependent protease (calpain) activation within 8 hours administration, caspase-3 not evident until 16 48 after treatment. The receptor antagonist MK-801 (dizocilpine) decreased calpain activity, but did alter activity. Similar MK-801, inhibitors (Z-Val-Phe.H Z-Leu-Phe-CONHEt) shifted morphology towards delayed, prevent, Together, indicate that following increased activity precedes activation, contributes necrotic morphology, facilitates accelerates