Abstract
Although the cellular form of the prion protein (PrP C) is critical for the development of prion disease through its conformational conversion into the infectious form (PrP Sc), the physiological role of PrP C is less clear. Using alkaline single-cell gel electrophoresis (the Comet assay), we show that expression of PrP C protects human neuroblastoma SH-SY5Y cells against DNA damage under basal conditions and following exposure to reactive oxygen species, either hydroxyl radicals following exposure to Cu 2+ or Fe 2+ or singlet oxygen following exposure to the photosensitizer methylene blue and white light. Cells expressing either PrPΔoct which lacks the octapeptide repeats or the prion-disease-associated mutants A116V or PG14 had increased levels of DNA damage compared to cells expressing PrP C. In PrP Sc-infected mouse ScN2a cells there was a significant increase in DNA damage over noninfected N2a cells (median tail DNA 2.87 and 7.33%, respectively). Together, these data indicate that PrP C has a critical role to play in protecting cells against reactive-oxygen-species-mediated DNA damage; a function which requires the octapeptide repeats in the protein, is lost in disease-associated mutants of the protein or upon conversion to PrP Sc, and thus provide further support for the neuroprotective role for PrP C.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call