title: NAPOR-3 RNA binding protein is required for apoptosis in hippocampus.
abstract: NAPOR-3 is a central nervous system RNA binding protein that is associated with downstream mRNA targets and has been demonstrated to be selectively overexpressed during apoptotic cell death. In this study, we first examined the regional distribution of NAPOR-3 mRNA in the adult rat brain by in situ hybridization: the transcript was abundantly expressed in many brain regions, mostly in gray matter, including the CA1-CA4 regions and dentate gyrus of the hippocampus, the piriform cortex and the cerebellar granule cell layer. We then investigated the role of NAPOR-3 in neuronal cell death by monitoring its mRNA and protein expression levels using semiquantitative RT-PCR and Western blotting, respectively. NAPOR-3 was overexpressed in rat organotypic slices exposed to staurosporine and to oxygen-glucose deprivation (OGD), an in vitro model of apoptotic cerebral ischemia, but not when exposed to glutamate toxicity. Our results also demonstrate that NAPOR-3 gene overexpression is an early step in the chain of signaling events leading to apoptosis, taking place upstream of caspase-3 activation. Finally, antisense-mediated downregulation of NAPOR-3 gene expression protected hippocampal cultures against OGD-induced apoptosis and prevented caspase-3 activation. Our results demonstrate that NAPOR-3 gene overexpression is necessary for the execution of OGD-induced programmed cell death.
authors.affiliation: Department of Anatomy, Histology and Forensic Medicine-Anatomy Section, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. apacini@unifi.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pacini
authors.forename: Annarita
authors.initials: A
authors.lastname: Toscano
authors.forename: Valentina
authors.initials: V
authors.lastname: Cesati
authors.forename: Andrea
authors.initials: A
authors.lastname: Cozzi
authors.forename: Elena
authors.initials: E
authors.lastname: Meli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Paternostro
authors.forename: Paolo
authors.initials: P
authors.lastname: Pacini
authors.forename: Domenico E
authors.initials: DE
authors.lastname: Pellegrini-Giampietro
mesh_terms: D000818:Animals; D017209:Apoptosis; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017403:In Situ Hybridization; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010101:Oxygen Consumption; D016601:RNA-Binding Proteins / Q000235:genetics*; D051381:Rats
chemical_list: D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D005947:Glucose