Lentiviral delivered siRNA against ICER protects primary cortical neurons from apoptosis caused by serum depriviation

• Autorzy: Klejman A. , Bieganska K. , Gierej D. , Kaczmarek L.
• Języki publikacji: EN

Abstrakty

EN

CREB activation and CREB-dependent signaling pathways are crucial for neuronal survival. The term ICER (inducible cAMP early repressor) refers to four protein isoforms that are all endogenous, inducible antagonists of CREB. It was previously shown, that all 4 ICER isoforms are induced upon pro-apoptotic treatment, and also that each of them separately evokes neuronal cell death in cortical culture transfected with these genes. The ICER proteins are believed to be strong repressors of Immediate Early Genes, which are involved in cell response to inter- and/or intra-cellular signals. Herein, we have applied the siRNA approach to silence ICER expression. Because ICERs are members of CREM family of proteins, sharing with them the gene sequence, only the small unique region for ICER was selected to design ICER-directed, specifi c siRNA. Indeed, we obtained functional siRNA capable of blocking ICERs but not affecting CREM proteins. With this tool, we have investigated if the ICER’s silencing protects neurons from apoptosis caused by either serum deprivation or excitotoxicity. Using the lentiviral vector, as a vehicle to deliver siRNA (shRNA) we have found that silencing of ICER mildly, although signifi cantly, protects primary cortical neurons from apoptosis caused by serum deprivation.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.316

Twórcy

autor

Klejman A.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Bieganska K.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Gierej D.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Kaczmarek L.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland