title: Platelet-activating factor mediates the cytotoxicity induced by W7FW14F apomyoglobin amyloid aggregates in neuroblastoma cells.
abstract: W7FW14F apomyoglobin (W7FW14F ApoMb) amyloid aggregates induce cytotoxicity in SH-SY5Y human neuroblastoma cells through a mechanism not fully elucidated. Amyloid neurotoxicity process involves calcium dyshomeostasis and reactive oxygen species (ROS) production. Another key mediator of the amyloid neurotoxicity is Platelet-Activating Factor (PAF), an inflammatory phospholipid implicated in neurodegenerative diseases. Here, with the aim at evaluating the possible involvement of PAF signaling in the W7FW14F ApoMb-induced cytotoxicity, we show that the presence of CV3899, a PAF receptor (PAF-R) antagonist, prevented the detrimental effect of W7FW14F ApoMb aggregates on SH-SY5Y cell viability. Noticeably, we found that the activation of PAF signaling, following treatment with W7FW14F ApoMb, involves a decreased expression of the PAF acetylhydroase II (PAF-AH II). Interestingly, the reduced PAF-AH II expression was associated with a decreased acetylhydrolase (AH) activity and to an increased sphingosine-transacetylase activity (TA(S)) with production of N-acetylsphingosine (C2-ceramide), a well known mediator of neuronal caspase-dependent apoptosis. These findings suggest that an altered PAF catabolism takes part to the molecular events leading to W7FW14F ApoMb amyloid aggregates-induced cell death.
authors: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors: Ivana
authors: I
authors: Sirangelo
authors: Alfonso
authors: A
authors: Giovane
authors: Rosa
authors: R
authors: Maritato
authors: Nunzia
authors: N
authors: D'Onofrio
authors: Clara
authors: C
authors: Iannuzzi
authors: Antonio
authors: A
authors: Giordano
authors: Gaetano
authors: G
authors: Irace
authors: Maria Luisa
authors: ML
authors: Balestrieri
mesh_terms: D000682:Amyloid / Q000502:physiology*; D001059:Apoproteins / Q000502:physiology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D009211:Myoglobin / Q000502:physiology*; D009447:Neuroblastoma; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D066329:Protein Aggregates; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D000682:Amyloid; D001059:Apoproteins; D009211:Myoglobin; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D066329:Protein Aggregates; D043562:Receptors, G-Protein-Coupled; C010857:apomyoglobin; C039351:platelet activating factor receptor; C037913:CV 3988
keywords: AMYLOID AGGREGATES; AMYLOID CYTOTOXICITY; PAF