title: Differentially expressed genes in iron-induced prion protein conversion.
abstract: The conversion of the cellular prion protein (PrPC) to the protease-resistant isoform is the key event in chronic neurodegenerative diseases, including transmissible spongiform encephalopathies (TSEs). Increased iron in prion-related disease has been observed due to the prion protein-ferritin complex. Additionally, the accumulation and conversion of recombinant PrP (rPrP) is specifically derived from Fe(III) but not Fe(II). Fe(III)-mediated PK-resistant PrP (PrPres) conversion occurs within a complex cellular environment rather than via direct contact between rPrP and Fe(III). In this study, differentially expressed genes correlated with prion degeneration by Fe(III) were identified using Affymetrix microarrays. Following Fe(III) treatment, 97 genes were differentially expressed, including 85 upregulated genes and 12 downregulated genes (≥1.5-fold change in expression). However, Fe(II) treatment produced moderate alterations in gene expression without inducing dramatic alterations in gene expression profiles. Moreover, functional grouping of identified genes indicated that the differentially regulated genes were highly associated with cell growth, cell maintenance, and intra- and extracellular transport. These findings showed that Fe(III) may influence the expression of genes involved in PrP folding by redox mechanisms. The identification of genes with altered expression patterns in neural cells may provide insights into PrP conversion mechanisms during the development and progression of prion-related diseases.
authors.affiliation: Laboratory of Immunology and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Minsun
authors.initials: M
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Laboratory of Immunology and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; Solomon Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, PCTB1004, 725 N Wolfe Street, Baltimore, MD, USA.
authors.forename: Bo-Ran
authors.initials: BR
authors.lastname: Choi
authors.affiliation: Laboratory of Immunology and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: hjwoo@snu.ac.kr.
authors.forename: Hee-Jong
authors.initials: HJ
authors.lastname: Woo
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007501:Iron / Q000494:pharmacology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018621:PrPC Proteins / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D018621:PrPC Proteins; D007501:Iron
keywords: Conversion; Gene expression; Iron; Microarray; Prion disease; Redox