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.

langueAnglais
journalMechanisms of Ageing and Development
Les DOIs
étatPublié - 2017

Empreinte digitale

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

mots-clés

    Citer ceci

    @article{455fd4a930cd43d8aa3c21a2554f2b4d,
    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 = "2017",
    doi = "10.1016/j.mad.2017.08.002",
    language = "English",
    journal = "Mechanisms of Ageing and Development",
    issn = "0047-6374",
    publisher = "Elsevier Ireland Ltd",

    }

    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, 2017.

    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 - 2017

    Y1 - 2017

    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

    KW - Prion protein

    KW - Senescence

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    U2 - 10.1016/j.mad.2017.08.002

    DO - 10.1016/j.mad.2017.08.002

    M3 - Article

    JO - Mechanisms of Ageing and Development

    T2 - Mechanisms of Ageing and Development

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    SN - 0047-6374

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