NR AXTR
AU Nordström,E.K.; Kristensson,K.
TI Involvement of the MEK1/2-ERK1/2 Signaling Pathway in Formation of Prions from Different Strains
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.38
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The MEK1/2-ERK1/2 signaling pathway plays a major role in cell proliferation and differentiation and is activated by growth factors, hormones and neurotransmitters. The cascade cooperates in the transmission of extracellular signals to their intracellular targets via sequential activation of protein kinases. We have previously shown that stimulation of the MEK1/2-ERK1/2 pathway leads to increased formation of PrPsc. Furthermore, we have shown that inhibition of MEK1/2 using specific inhibitors (U0126, PD098059, SL327) clears gonadotropin-releasing hormone-secreting neuronal cells (GT1-1 cells), infected with the RML strain of scrapie, from PrPsc.
In order to examine if the activity of MEK1/2 and ERK1/2 is affected by a scrapie infection, we inoculated GT1-1 cells with brain homogenate from mice infected with the scrapie strains RML, 22L and Me7. Inoculation of GT1-1 cells with RML and 22L resulted in persistently infected cells, while inoculation with Me7 did not lead to accumulation of proteinase K resistant PrPsc. Cells were harvested every other passage after infection and the levels of activated (phosphorylated) MEK1/2 and ERK1/2 was analyzed by Western blot. Furthermore, we wanted to investigate if MEK1/2 inhibitors could be effective in curing GT1-1 cells infected with other scrapie strains and preliminary results indicate that the levels of PrPsc in GT1-1 cells infected with 22L can be decreased by treatment with the MEK1/2 inhibitor U0126. In this project we will characterize the involvement of MEK1/2-ERK1/2 in formation of PrPsc from different scrapie strains and thus increase the basic knowledge about the metabolism of prions.
This research was supported by LSSG-CT-2006-037654.
AD E. Nordström, K. Kristensson, Karolinska Institutet, Neuroscience, Sweden
SP englisch
PO Schottland