title: PKC delta and NADPH oxidase in AGE-induced neuronal death.
abstract: Advanced glycation end product (AGE) accumulation in brain is believed to contribute to neuronal death in several neurodegenerative diseases. Neurons exposed to AGEs undergo oxidative stress, but the molecular mechanisms able to induce ROS generation and cell death are not yet clear. In this work, we exposed SH-SY5Y neuroblastoma cells to glycated albumin, as a model of AGE-modified protein, and we observed that cells differentiated by retinoic acid died after AGE exposure, through anion superoxide and peroxide generation, while undifferentiated cells resulted resistant. Retinoic acid induced marked increase in p47phox expression and in catalytic activity of PKC delta: the upregulation of a pathway involving NADPH oxidase and PKC delta is likely to be responsible for neuronal susceptibility to AGE. This hypothesis is confirmed by the fact that pre-treatments of differentiated cells with DPI, an inhibitor of NADPH oxidase, or with rottlerin, an inhibitor of PKC delta, were able to prevent AGE-induced neuronal death.
authors.affiliation: Department of Experimental Medicine, General Pathology Section, University of Genoa, Via L.B. Alberti 2, 16132 Genoa, Italy. paonit@medicina.unige.it
authors.forename: Mariapaola
authors.initials: M
authors.lastname: Nitti
authors.forename: Anna L
authors.initials: AL
authors.lastname: Furfaro
authors.forename: Nicola
authors.initials: N
authors.lastname: Traverso
authors.forename: Patrizio
authors.initials: P
authors.lastname: Odetti
authors.forename: Daniela
authors.initials: D
authors.lastname: Storace
authors.forename: Damiano
authors.initials: D
authors.lastname: Cottalasso
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pronzato
authors.forename: Umberto M
authors.initials: UM
authors.lastname: Marinari
authors.forename: Cinzia
authors.initials: C
authors.lastname: Domenicotti
mesh_terms: D000704:Analysis of Variance; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C000593871:AGER protein, human; D017127:Glycation End Products, Advanced; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D014212:Tretinoin; D019255:NADPH Oxidases; D051745:Protein Kinase C-delta; D020928:Mitogen-Activated Protein Kinases