Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells

Castorina, A; Giunta, S; Scuderi, S; D'Agata, V

Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells

Castorina, A

Giunta, S Scuderi, S D'Agata, V

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Publication Type:: Journal Article
Citation:: Journal of Molecular Neuroscience, 2012, 48 (3), pp. 674 - 683
Issue Date:: 2012-11-01

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Field	Value	Language
dc.contributor.author	Castorina, A https://orcid.org/0000-0001-7037-759X	en_US
dc.contributor.author	Giunta, S	en_US
dc.contributor.author	Scuderi, S	en_US
dc.contributor.author	D'Agata, V	en_US
dc.date.available	2012-03-16	en_US
dc.date.issued	2012-11-01	en_US
dc.identifier.citation	Journal of Molecular Neuroscience, 2012, 48 (3), pp. 674 - 683	en_US
dc.identifier.issn	0895-8696	en_US
dc.identifier.uri	http://hdl.handle.net/10453/115237
dc.description.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. © Springer Science+Business Media, LLC 2012.	en_US
dc.relation.ispartof	Journal of Molecular Neuroscience	en_US
dc.relation.isbasedon	10.1007/s12031-012-9755-z	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Tumor Cells, Cultured	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Hydrogen Peroxide	en_US
dc.subject.mesh	Neoplasm Proteins	en_US
dc.subject.mesh	Nerve Tissue Proteins	en_US
dc.subject.mesh	DNA, Neoplasm	en_US
dc.subject.mesh	Culture Media, Serum-Free	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Apoptosis	en_US
dc.subject.mesh	DNA Replication	en_US
dc.subject.mesh	Gene Expression Regulation, Neoplastic	en_US
dc.subject.mesh	Dose-Response Relationship, Drug	en_US
dc.subject.mesh	Nerve Sheath Neoplasms	en_US
dc.subject.mesh	Pituitary Adenylate Cyclase-Activating Polypeptide	en_US
dc.subject.mesh	Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I	en_US
dc.subject.mesh	Receptors, Vasoactive Intestinal Peptide, Type II	en_US
dc.subject.mesh	Real-Time Polymerase Chain Reaction	en_US
dc.title	Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	48	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1702 Cognitive Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	48	en_US

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. © Springer Science+Business Media, LLC 2012.

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http://hdl.handle.net/10453/115237