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Quantitative comparison of ferritin iron and levels of ferritin, Tf, and TfR shows
signifi cant differences between cell lines. Thus, relative to M17 cells, PrP C cells show
an increase in ferritin iron and ferritin levels to 570 and 565%, and a decrease in Tf and
TfR levels to 70 and 75% respectively. A similar comparison of mutant cell lines rela-
tive to PrP C cells shows the following: PrP Δ51-89 cells show a decrease in ferritin iron
and ferritin to 7.0, 6.9%, and insignifi cant change in Tf and TfR levels. PrP Δ23-89 cells
show a similar decrease in ferritin iron and ferritin levels to 7.5 and 7.2%, an increase
in Tf to 120%, and insignifi cant change in TfR levels. PrP 102L -cells show a decrease
in ferritin iron and ferritin levels to 89 and 90%, and an increase in Tf and TfR levels
to 300 and 142% respectively. The PrP 231stop cells show a decrease in ferritin iron and
ferritin to 27 and 16%, and a decrease in Tf and TfR levels to 89 and 67% respectively.
Quantifi cation of PrP expression relative to M17 shows levels of 650, 710, 750, 610,
and 5% in PrP C , PrP Δ51-89 , PrP Δ23-89 , PrP 102L , and PrP 231stop cells respectively (Figure 4).
Figure 4. Quantitative analysis of the results in Figures 1-3. Quantitative evaluation after densitometry
of ferritin iron and levels of PrP, ferritin, Tf, and TfR in PrP C , PrP Δ 51-89 , PrP Δ 23-89 , PrP 102L , PrP 231stop -cells
relative to non-transfected M17 controls. Values are mean±SEM of 11 independent experiments. The
y-scale is linear but has been re-scaled after the break to illustrate the data clearly. For M17 vs. PrP C
*p<0.001, **p<0.01, and for PrP C vs. mutant cell lines # p<0.001, ## p<0.01).
Considering the tightly orchestrated and coordinated balance between cellular iron
levels and iron uptake and storage proteins [18, 21], these results indicate a mild iron
overload in PrP C -cells relative to M17-cells, and an indefi nable phenotype in mutant
cell lines since the iron uptake proteins Tf and TfR do not respond to ferritin iron
levels as expected. Since Tf and TfR levels are refl ective of the biologically available
intracellular LIP that is maintained within the physiological range by ferritin, these
results indicate a disconnect between ferritin iron and the cellular LIP, or a failure of
the iron regulatory loop involving the LIP, iron binding proteins 1 and 2, TfR, and fer-
ritin to induce appropriate response.
 
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