新規PACAP誘導体のグリア細胞を介する脳保護効果

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  • Neuroprotective effects of a novel PACAP derivative depending on presence of glia cells

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Despite the neuroprotective properties of pituitary adenylate cyclase activating polypeptide (PACAP), its use as a drug is limited by its susceptibility to endopeptidases. In this experiment, we examined the neuroprotective effects of a novel PACAP derivative, ac-PACAP30 on brain neuronal death induced by a 1 mM glutamate (Glu) . Primary cultured rat cerebellar granule cells were prepared to the neuron rich cell group (neuron: glia=9: 1) and the neuron/glia cocultured cell group (neuron: glia=6: 4) . The concentrations between 1 and 1000fM of ac-PACAP30 were incubated with Glu contained Krebs-HEPES buffer for 20 hr at 37°C. Cell injury was assayed with a calcein-AM. Extracellular levels of IL-6 and GM-CSF were measured using rat ELISA kits, respectively. The significant inhibitions of ac-PACAP30 on the cell death induced by Glu were seen at more than 10 fM in the cocultured cells, but not the neuron rich cells. Further ac-PACAP30 given 30min after Glu treatment caused the significant neuroprotection. In the cocultured cells, but not the neuron-rich cell cultures, acPACAP30 significantly increased IL-6 and GM-CSF levels for 30min in stimulated condition, dose-dependently. These results indicate that ac-PACAP30 showed the strong neuroprotective property at its low concentration due to the increases of IL-6 and GM-CSF from astrocyte.

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  • 蘇生

    蘇生 24 (1), 10-16, 2005

    日本蘇生学会

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