Identification of functionally relevant proteins in neuronal cells through coupled microarray and siRNA screening: Role of a novel selenoprotein in calcium regulation and Neuroprotection
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1
Laboratory of Neuronal and Neuroendocrine Communication and differentiation, INSERM Unit 413, Laboratory of Cellular and Molecular Neuroendocrinology, France
Pangenomic microarray screening of differentiating neuronal cells may enable identifying new genes with essential functions in the CNS, during development and adulthood. Analysis of the transcriptome of sympathetic neuronal cells after differentiation with the neurotrophic factor PACAP, using a developmentally oriented gene microarray, revealed the alteration of the expression of several novel genes with unknown function. Among these, we have focused our attention on selenoprotein T (SelT) which belongs to a family of selenium-containing proteins. Selenoproteins are involved in the catalysis of a variety of redox reactions, including reduction of ROS under oxidative stress. We have used in vitro and in vivo gene knockout experiments to decipher the role of SelT in nerve cells. Using confocal microscopy and siRNA treatment, we first showed that SelT is an ER-resident protein involved in the PACAP-induced calcium increase in PC12 cells. We confirmed the association of increased SelT gene expression and cell differentiation in several tissues, including the brain. In addition, while SelT gene expression was almost undetectable in the adult brain, except in few immature cells, a dramatic increase in SelT mRNA and protein was observed in astrocytes following cerebral ischemia. This finding suggests that SelT may participate to the neuroprotective astroglial reaction. Finally, SelT gene ablation in mice is lethal in utero, indicating that the activity of this novel selenoprotein is crucial during early development. These data demonstrate the usefulness of gene expression profiling of neuronal cells in order to uncover novel genes with important activities in the brain such as SelT, a novel selenoprotein probably involved in the regulation of calcium and reactive oxygen species through a redox mechanism.
Supported by INSERM (U413), University of Rouen (EA 4310) and the Conseil Regional de Haute-Normandie.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Symposium 15 – NeuroGenomics, Discovering New Genes and Pathophysiological Mechanisms with Phosphoproteomics and Transcriptomics
Citation:
Anouar
Y
(2009). Identification of functionally relevant proteins in neuronal cells through coupled microarray and siRNA screening: Role of a novel selenoprotein in calcium regulation and Neuroprotection.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.063
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Received:
19 Nov 2009;
Published Online:
19 Nov 2009.
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Correspondence:
Youssef Anouar, Laboratory of Neuronal and Neuroendocrine Communication and differentiation, INSERM Unit 413, Laboratory of Cellular and Molecular Neuroendocrinology, Mont-Saint-Aignan, France, youssef.anouar@univ-rouen.fr