NR AWLE
AU Nouvel,V.; Picoli,C.; Lenuzza,N.; Aubry,F.; Charveriat,M.; Correia,E.; Reboul,M.; Guegan,N.; Bailly,Y.; Deslys,J.P.; Mouthon,F.
TI Prnp gene regulation during prion infection and cell differentiation
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions DIA-40
PT Konferenz-Poster
AB Prnp is considered as a housekeeping gene and the amount of PrPc during Prion infection is considered as constant during all the disease. However, an overexpression of PrPc is also described during neuronal differentiation via ERK1/2 pathway activation. Using a magnetic cell sorting, based on surface PrP level previously developed in the laboratory, we observed a different PrPc expression between infected cells versus controls. To understand this modification of metabolism of the normal PrP, we focused on the transcriptional regulation of Prnp during prion infection and in different states of cellular differentiation. We examined ERK1/2 and Notch pathways, already described as involved during prion infection. The studies were performed in different cell lines (GT-1, SN56) infected or not with the Chandler scrapie strain while cAMP and Notch inhibitor treatments were used for differentiation experiments. Notch inhibitor treatments decreased phosphorylated ERK 1/2 and phosphoSTAT in all cell lines and increased the level of PrPres in infected cells. Surprisingly the expression of HES5 (under phosphoSTAT transcriptional regulation) was decreased only in infected cells. Moreover, the expression of a GFP construct, under the control of different regulatory sequences of the murine prion promoter, appeared in preliminary experiments to react differently to Notch inhibitor treatments depending on the infected status of the cells. Thus, the metabolic pathways involved during prion infection could lead to variations of PrPc synthesis. Elucidation of the molecular mechanisms involved, and more precisely in Prnp promoter regulation, should offer a new insight to the comprehension of cellular susceptibility to Prion replication.
AD V. Nouvel, C. Picoli, N. Lenuzza, F. Aubry, M. Charveriat, E. Correia, M. Reboul, N. Guegan, J.-P. Deslys, F. Mouthon: CEA/DSV/DRM/GIDTIP, Fontenay-aux-Roses, France; Y. Bailly: Neurotransmission & Secretion Neuroendocrine, CNRS UPR2356, Strasbourg, France
SP englisch
PO Italien