VIP and peptides related to activity-dependent neurotrophic factor protect PC12 cells against oxidative stress

R. A. Steingart, B. Solomon, D. E. Brenneman, M. Fridkin, I. Gozes

Research output: Contribution to journalArticlepeer-review


Oxidative stress is a common associative mechanism that is part of the pathogenesis of many neurodegenerative diseases. Vasoactive intestinal peptide (VIP) is a principal neuropeptide associated with normal development and aging. We have previously reported that VIP induced the secretion of proteins from glial cells, including the novel survival-promoter: activity-dependent neurotrophic factor (ADNF). ADNF-9, a nine amino acid peptide derived from ADNF, protects neurons from death caused by various toxins. In the present study, we examined the neuroprotective effect of VIP against oxidative stress in a pheochromocytoma cell line (PC12). In addition, a lipophilic derivative of VIP, Stearyl-Nle17-VIP (SNV), and two femtomolar-acting peptides: ADNF-9 and a 70% homologous peptide to ADNF-9, NAP were tested as well. PC12 cells were treated with 100 μM H2O2 for 24 h resulting in a reduction in cell survival to 35-50% as compared to controls. Addition of VIP or SNV prior and during the exposure to 100 μM H2O2 increased cell survival to 80-90% of control values. Culture treatment with ADNF-9 or NAP in the presence of 100 μM H2O2 increased cell survival to 75-80% of control values. Messenger RNA expression analysis revealed that incubation with VIP resulted in a twofold increase in VIP mRNA, whereas NAP treatment did not cause any change in VIP expression, implicating different mechanisms of action. Furthermore, addition of an ADNF-9 antibody prevented the ability of VIP to protect against oxidative stress, suggesting that VIP protection is partially mediated via an ADNF-like protein.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalJournal of Molecular Neuroscience
Issue number3
StatePublished - 2000


FundersFunder number
Institute for the Study of Aging
US-Israel Binational Science Foundation
Bloom's Syndrome Foundation
Israel Science Foundation


    • ADNP-9
    • HO
    • NAP
    • PC12
    • RT-PCR
    • Rat
    • VIP


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