Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 43, Issue 6, Pages 959-967Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2007.06.004
Keywords
prion; DNA damage; reactive oxygen species; comet assay; copper
Funding
- MRC [G9824728] Funding Source: UKRI
- Medical Research Council [G9824728] Funding Source: researchfish
- Medical Research Council [G9824728] Funding Source: Medline
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Although the cellular form of the prion protein (PrPC) is critical for the development of prion disease through its conformational conversion into the infectious form (PrPSc), the physiological role of PrPC is less clear. Using alkaline single-cell gel electrophoresis (the Comet assay), we show that expression of PrPC 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 Cu2+ or Fe2+ or singlet oxygen following exposure to the photosensitizer methylene blue and white light. Cells expressing either PrP Delta oct which lacks the octapeptide repeats or the prion-disease-associated mutants A116V or PG14 had increased levels of DNA damage compared to cells expressing PrPc. In PrPSc-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 PrPc 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 PrPSc, and thus provide further support for the neuroprotective role for PrPc. (c) 2007 Published by Elsevier Inc.
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