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

Eur J Pharmacol. 2009 Sep 15;618(1-3):9-14. doi: 10.1016/j.ejphar.2009.07.013. Epub 2009 Jul 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / drug effects*
  • Cytochromes c / metabolism*
  • Glucose / deficiency
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Nerve Tissue Proteins / chemistry
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Oxygen / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Staining and Labeling


  • Nerve Tissue Proteins
  • Oligopeptides
  • Cytochromes c
  • Glucose
  • Oxygen