Recombinant activity-dependent neuroprotective protein protects cells against oxidative stress

Mol Cell Endocrinol. 2006 Jun 27;252(1-2):148-53. doi: 10.1016/j.mce.2006.03.029. Epub 2006 May 15.


Activity-dependent neuroprotective protein (ADNP) is essential for brain formation. Here, we investigated the potential neuroprotective effects of recombinant ADNP under stress conditions. The human ADNP cDNA was sub-cloned into a vector that contains VP22, a Herpes virus protein that may allow penetration of fused proteins through cellular membranes. When incubated with pheochromocytoma (PC12) cells, a neuronal model, VP22-ADNP was associated with the cells after a 25-min incubation period. Pre-incubation with VP22-ADNP enriched protein fractions protected against beta amyloid peptide toxicity and oxidative stress (H2O2) in PC12 cells. VP22 by itself was devoid of protective activity. Furthermore, the pro-apoptotic protein p53 increased by 3.5-fold from control levels in the presence of H2O2, while treatment with VP22-ADNP prior to H2O2 exposure significantly reduced the p53 protein levels. ADNP expression was previously shown to oscillate as a function of the estrus cycle in the mouse arcuate nucleus, these oscillations are now correlated with increased cellular protection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyloid / toxicity
  • Animals
  • Cloning, Molecular
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / pharmacology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / pharmacology
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • PC12 Cells
  • Rats
  • Recombinant Fusion Proteins / pharmacology
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / pharmacology


  • ADNP protein, human
  • Amyloid
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Recombinant Fusion Proteins
  • VP22 protein, Pseudorabies virus
  • Viral Structural Proteins