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

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Abstract

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.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Sackler Medical School, Tel Aviv University, 69978, Tel Aviv, Israel

    Ruth A. Steingart & Illana Gozes

  2. Department of Molecular Microbiology and Biotechnology, Wise Faculty of Life Sciences, Tel-Aviv University, 69978, Tel Aviv, Israel

    Beka Solomon

  3. Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD

    Douglas E. Brenneman

  4. Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Mati Fridkin

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  1. Ruth A. Steingart
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  2. Beka Solomon
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  3. Douglas E. Brenneman
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  4. Mati Fridkin
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  5. Illana Gozes
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Steingart, R.A., Solomon, B., Brenneman, D.E. et al. VIP and peptides related to activity-dependent neurotrophic factor protect PC12 cells against oxidative stress. J Mol Neurosci 15, 137–145 (2000). https://doi.org/10.1385/JMN:15:3:137

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  • DOI: https://doi.org/10.1385/JMN:15:3:137

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