TY - JOUR
T1 - Recombinant activity-dependent neuroprotective protein protects cells against oxidative stress
AU - Steingart, R. A.
AU - Gozes, I.
N1 - Funding Information:
We thank Dr. Douglas E. Brenneman and Mrs. Irit Spivak for critical reading of the manuscript. This study was supported by ISF, BSF, ISOA and Allon Therapeutics, Inc. Professor Illana Gozes is the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and heads, the Dr. Diana and Zelman Elton (Elbaum) Laboratory for Molecular Neuroendocrinology. Professor Illana Gozes serves as the Chief Scientific Officer at Allon Therapeutics Inc.
PY - 2006/6/27
Y1 - 2006/6/27
N2 - 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 β 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.
AB - 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 β 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.
KW - Activity-dependent neuroprotective protein (ADNP)
KW - Neuroprotection
KW - Oxidative stress
KW - P53
KW - Pheochromocytoma (PC12)
KW - β Amyloid 25-35
UR - http://www.scopus.com/inward/record.url?scp=33745223638&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2006.03.029
DO - 10.1016/j.mce.2006.03.029
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:33745223638
VL - 252
SP - 148
EP - 153
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -