Recombinant activity-dependent neuroprotective protein protects cells against oxidative stress.
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.
Steingart
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RA
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Gozes
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D000682:Amyloid / Q000633:toxicity; D000818:Animals; D003001:Cloning, Molecular; D018398:Homeodomain Proteins / Q000235:genetics / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015678:Viral Structural Proteins / Q000235:genetics / Q000494:pharmacology
C492178:ADNP protein, human; D000682:Amyloid; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; C502892:VP22 protein, Pseudorabies virus; D015678:Viral Structural Proteins