title: Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells.
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 (H(2)O(2))-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. PAC(1)/VPAC receptor antagonists completely suppressed PACAP-stimulated ADNP increase and partially reduced ADNP expression in SS cells. NS-cultured cells exposed to H(2)O(2) showed significantly reduced cell viability (~50 %), increased p53 and caspase-3, and DNA fragmentation, without affecting ADNP expression. Serum starvation significantly reduced H(2)O(2)-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 H(2)O(2)-induced death upon serum starvation.
authors.affiliation: Department of Bio-Medical Sciences, University of Catania, Via S.Sofia 87, 95123, Catania, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Castorina
authors.forename: Salvatore
authors.initials: S
authors.lastname: Giunta
authors.forename: Soraya
authors.initials: S
authors.lastname: Scuderi
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D009363:Neoplasm Proteins / Q000502:physiology*; D018317:Nerve Sheath Neoplasms / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology* / Q000502:physiology*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000037:antagonists & inhibitors / Q000502:physiology; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C579795:ADNP protein, rat; D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D006861:Hydrogen Peroxide