Résumé

Prion protein (PrP) is essentially known for its capacity to induce neurodegenerative prion diseases in mammals caused by a conformational change in its normal cellular isoform (PrPC) into an infectious and disease-associated misfolded form, called scrapie isoform (PrPSc). Although its sequence is highly conserved, less information is available on its physiological role under normal conditions. However, increasing evidence supports a role for PrPC in the cellular response to oxidative stress. In the present study, a new link between PrP and senescence is highlighted. The role of PrP in premature senescence induced by copper was investigated. WI-38 human fibroblasts were incubated with copper sulfate (CuSO4) to trigger premature senescence. This induced an increase of PrP mRNA level, an increase of protein abundance of the normal form of PrP and a nuclear localization of the protein. Knockdown of PrP expression using specific small interfering RNA (siRNA) gave rise to appearance of several biomarkers of senescence as a senescent morphology, an increase of senescence associated β-galactosidase activity and a decrease of the cellular proliferative potential. Overall these data suggest that PrP protects cells against premature senescence induced by copper.

langue originaleAnglais
Pages (de - à)106-113
Nombre de pages8
journalMechanisms of Ageing and Development
Volume170
Les DOIs
étatPublié - 1 mars 2018

Empreinte digitale

Fibroblasts
Copper
Protein Isoforms
Galactosidases
Copper Sulfate
Scrapie
Prion Diseases
Nuclear Proteins
Prion Proteins
Neurodegenerative Diseases
Small Interfering RNA
Communicable Diseases
Mammals
Oxidative Stress
Biomarkers
Messenger RNA
Proteins

Citer ceci

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title = "Role of Prion protein in premature senescence of human fibroblasts",
abstract = "Prion protein (PrP) is essentially known for its capacity to induce neurodegenerative prion diseases in mammals caused by a conformational change in its normal cellular isoform (PrPC) into an infectious and disease-associated misfolded form, called scrapie isoform (PrPSc). Although its sequence is highly conserved, less information is available on its physiological role under normal conditions. However, increasing evidence supports a role for PrPC in the cellular response to oxidative stress. In the present study, a new link between PrP and senescence is highlighted. The role of PrP in premature senescence induced by copper was investigated. WI-38 human fibroblasts were incubated with copper sulfate (CuSO4) to trigger premature senescence. This induced an increase of PrP mRNA level, an increase of protein abundance of the normal form of PrP and a nuclear localization of the protein. Knockdown of PrP expression using specific small interfering RNA (siRNA) gave rise to appearance of several biomarkers of senescence as a senescent morphology, an increase of senescence associated β-galactosidase activity and a decrease of the cellular proliferative potential. Overall these data suggest that PrP protects cells against premature senescence induced by copper.",
keywords = "Copper, Fibroblasts, Oxidative stress, Prion protein, Senescence",
author = "Emmanuelle Boilan and Virginie Winant and {\'E}lise Dumortier and Bena{\"i}ssa Elmoualij and Pascale Quatresooz and Osiewacz, {Heinz D.} and Florence Debacq-Chainiaux and Olivier Toussaint",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.mad.2017.08.002",
language = "English",
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pages = "106--113",
journal = "Mechanisms of Ageing and Development",
issn = "0047-6374",
publisher = "Elsevier Ireland Ltd",

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Role of Prion protein in premature senescence of human fibroblasts. / Boilan, Emmanuelle; Winant, Virginie; Dumortier, Élise; Elmoualij, Benaïssa ; Quatresooz, Pascale; Osiewacz, Heinz D.; Debacq-Chainiaux, Florence; Toussaint, Olivier.

Dans: Mechanisms of Ageing and Development, Vol 170, 01.03.2018, p. 106-113.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Role of Prion protein in premature senescence of human fibroblasts

AU - Boilan, Emmanuelle

AU - Winant, Virginie

AU - Dumortier, Élise

AU - Elmoualij, Benaïssa

AU - Quatresooz, Pascale

AU - Osiewacz, Heinz D.

AU - Debacq-Chainiaux, Florence

AU - Toussaint, Olivier

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Prion protein (PrP) is essentially known for its capacity to induce neurodegenerative prion diseases in mammals caused by a conformational change in its normal cellular isoform (PrPC) into an infectious and disease-associated misfolded form, called scrapie isoform (PrPSc). Although its sequence is highly conserved, less information is available on its physiological role under normal conditions. However, increasing evidence supports a role for PrPC in the cellular response to oxidative stress. In the present study, a new link between PrP and senescence is highlighted. The role of PrP in premature senescence induced by copper was investigated. WI-38 human fibroblasts were incubated with copper sulfate (CuSO4) to trigger premature senescence. This induced an increase of PrP mRNA level, an increase of protein abundance of the normal form of PrP and a nuclear localization of the protein. Knockdown of PrP expression using specific small interfering RNA (siRNA) gave rise to appearance of several biomarkers of senescence as a senescent morphology, an increase of senescence associated β-galactosidase activity and a decrease of the cellular proliferative potential. Overall these data suggest that PrP protects cells against premature senescence induced by copper.

AB - Prion protein (PrP) is essentially known for its capacity to induce neurodegenerative prion diseases in mammals caused by a conformational change in its normal cellular isoform (PrPC) into an infectious and disease-associated misfolded form, called scrapie isoform (PrPSc). Although its sequence is highly conserved, less information is available on its physiological role under normal conditions. However, increasing evidence supports a role for PrPC in the cellular response to oxidative stress. In the present study, a new link between PrP and senescence is highlighted. The role of PrP in premature senescence induced by copper was investigated. WI-38 human fibroblasts were incubated with copper sulfate (CuSO4) to trigger premature senescence. This induced an increase of PrP mRNA level, an increase of protein abundance of the normal form of PrP and a nuclear localization of the protein. Knockdown of PrP expression using specific small interfering RNA (siRNA) gave rise to appearance of several biomarkers of senescence as a senescent morphology, an increase of senescence associated β-galactosidase activity and a decrease of the cellular proliferative potential. Overall these data suggest that PrP protects cells against premature senescence induced by copper.

KW - Copper

KW - Fibroblasts

KW - Oxidative stress

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