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Involvement of PACAP/ADNP Signaling in the Resistance to Cell Death in Malignant Peripheral Nerve Sheath Tumor (MPNST) Cells

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Abstract

Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas able to grow under conditions of metabolic stress caused by insufficient nutrients or oxygen. Both pituitary adenylate cyclase-activating polypeptide (PACAP) and activity-dependent neuroprotective protein (ADNP) have glioprotective potential. However, whether PACAP/ADNP signaling is involved in the resistance to cell death in MPNST cells remains to be clarified. Here, we investigated the involvement of this signaling system in the survival response of MPNST cells against hydrogen peroxide (H2O2)-evoked death both in the presence of normal serum (NS) and in serum-starved (SS) cells. Results showed that ADNP levels increased time-dependently (6–48 h) in SS cells. Treatment with PACAP38 (10−9 to 10−5 M) dose-dependently increased ADNP levels in NS but not in SS cells. PAC1/VPAC receptor antagonists completely suppressed PACAP-stimulated ADNP increase and partially reduced ADNP expression in SS cells. NS-cultured cells exposed to H2O2 showed significantly reduced cell viability (~50 %), increased p53 and caspase-3, and DNA fragmentation, without affecting ADNP expression. Serum starvation significantly reduced H2O2-induced detrimental effects in MPNST cells, which were not further ameliorated by PACAP38. Altogether, these finding provide evidence for the involvement of an endogenous PACAP-mediated ADNP signaling system that increases MPNST cell resistance to H2O2-induced death upon serum starvation.

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Acknowledgments

These experiments were partially funded by Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN grant no. 2007SXKWSA) and were supported by the International PhD program in Neuropharmacology, University of Catania, Medical School. We thank Mr P. Asero for his technical support and Dr. F. Murabito for his administrative support. All authors declare that there are no competing interests.

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Authors and Affiliations

  1. Department of Bio-Medical Sciences, University of Catania, Via S.Sofia, 87, 95123, Catania, Italy

    Alessandro Castorina, Salvatore Giunta, Soraya Scuderi & Velia D’Agata

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  1. Alessandro Castorina
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  2. Salvatore Giunta
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  3. Soraya Scuderi
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  4. Velia D’Agata
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Correspondence to Velia D’Agata.

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Castorina, A., Giunta, S., Scuderi, S. et al. Involvement of PACAP/ADNP Signaling in the Resistance to Cell Death in Malignant Peripheral Nerve Sheath Tumor (MPNST) Cells. J Mol Neurosci 48, 674–683 (2012). https://doi.org/10.1007/s12031-012-9755-z

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  • DOI: https://doi.org/10.1007/s12031-012-9755-z

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