期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 618, 期 1-3, 页码 9-14出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2009.07.013
关键词
Neuroprotection; Microtubule; Oxygen-glucose deprivation; Cytochrome c; Cortical neuron; Neuroprotective peptide
NAPVSIPQ (NAP), an 8 amino acid peptide derived from activity-dependent neuroprotective protein (ADNP), provides neuroprotection through interaction with microtubules. Previous results have demonstrated NAP protection against oxygen-glucose deprivation in hippocampal cells in culture. Furthermore, in vivo studies have shown that NAP reduces caspase 3 activation in rats subjected to permanent mid-cerebral artery occlusion (a rat model of stroke). Oxygen-glucose deprivation (ischemia) has been associated with microtubule breakdown and cytochrome c release from mitochondria leading to apoptosis. Here, NAP in concentrations ranging from 10(-14) M to 10(-8) M Completely blocked cytochrome c release in cortical neurons subjected to oxygen-glucose deprivation. Furthermore, quantitative microscopy coupled to microtubule immunocytochemistry suggested that NAP prevented microtubule degradation under oxidative stress. As cytochrome c release is a known initiator of the apoptotic pathway, it is suggested that NAP inhibits the early events of apoptosis. (C) 2009 Elsevier B.V. All rights reserved.
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