NAPOR-3 RNA binding protein is required for apoptosis in hippocampus

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...

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Published in:Brain research. Molecular brain research. 2005-10, Vol.140 (1), p.34-44
Main Authors: Pacini, Alessandra, Toscano, Annarita, Cesati, Valentina, Cozzi, Andrea, Meli, Elena, Di Cesare Mannelli, Lorenzo, Paternostro, Ferdinando, Pacini, Paolo, Pellegrini-Giampietro, Domenico E.
Format: Article
Language:English
Subjects:
Animals
Antisense oligonucleotide
Apoptosis
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Glucose - metabolism
Hippocampus - cytology
Hippocampus - physiology
In Situ Hybridization
Ischemic injury
Nerve Tissue Proteins - genetics
Oxygen Consumption
Rat organotypic hippocampal slice
Rats
RNA-Binding Proteins - genetics
Vertebrates: nervous system and sense organs
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Summary: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.
ISSN:0169-328X
1872-6941
DOI:10.1016/j.molbrainres.2005.07.006