NAP protects against cytochrome c release: Inhibition of the initiation of apoptosis

Ilona Zemlyak, Robert Sapolsky, Illana Gozes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalEuropean Journal of Pharmacology
Volume618
Issue number1-3
DOIs
StatePublished - 15 Sep 2009

Funding

FundersFunder number
Allon Therapeutics Inc.
United States-Israel Binational Science Foundation

    Keywords

    • Cortical neuron
    • Cytochrome c
    • Microtubule
    • Neuroprotection
    • Neuroprotective peptide
    • Oxygen-glucose deprivation

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