Differentially expressed genes in prion protein conversion induced by trivalent iron

Abstract

The conversion of the cellular prion protein (PrPc) to protease-resistant isoform is the key event in chronic neurodegenerative diseases including transmissible spongiform encephalopathies (TSEs). Increase of iron in prion related disease has been observed due to the prion protein-ferritin complex. The accumulation and conversion of recombinant PrP (rPrP) was specifically derived by Fe(III) but not by Fe(II). Fe(III)-mediated PK-resistant PrP (PrPres) conversion was conducted with a more complex cellular environment instead of a direct contact between rPrP and Fe(III). In this study, the differentially expressed genes that correlate with the prion degeneration by Fe(III) were identified using Affymetrix microarrays. In Fe(III)-treated environment, 97 genes were differentially expressed, 85 upregulated and 12 downregulated (≥1.5-fold change in expression). However, Fe(II)-treated environment produced moderately altered gene expression level and did not induce a dramatic alteration of gene expression profile. Moreover, functional grouping of identified genes indicated that the differentially regulated genes were highly associated with cell growth and maintenance, intra and extracellular transport environments. These findings show that Fe(III) might influence the expression of genes for PrP folding by redox mechanism. The identification of genes with altered expression patterns in neural cells may provide insight to the PrP conversion mechanisms in development and progression of prion related diseases.