A human clonal cell line model of differentiating neurons

J. R. Perez-Polo, K. Werrbach-Perez, E. Tiffany-Castiglioni

    Research output: Contribution to journalArticle

    94 Citations (Scopus)

    Abstract

    The human neuroblastoma cell line SK-N-SH and its thrice-subcloned derivative, SY-5Y, are nearly diploid cell lines with high levels of dopamine β-hydroxylase, a key enzyme in adrenergic neurotransmitter synthesis. The SY-5Y subclone also displays a neuroblast-like morphology in cell culture and in the undifferentiated state does not have electrically excitable membranes. In this study the response of the SY-5Y cells to the nerve growth factor protein, NGF, is described. After 5 days in culture in the presence of NGF, the SY-5Y cells extended neurites, ceased multiplying, and aggregated into clumps similar to those observed in primary cultures of sympathetic ganglia treated with NGF. Ultrastructural analysis of the induced processes showed them to be neurites. Whereas NGF treatment inhibited the incorporation of [3H]thymidine into DNA and inhibited cellular proliferation, it stimulated incorporation of3H-amino acids into protein. Further analysis of these differentiated cells showed them to have developed electrically excitable membranes. Undifferentiated cells were selectively killed by 6-hydroxydopamine, whereas NGF treatment led to protection of the differentiated cells from 6-hydroxydopamine killing. Treatment of the SY-5Y clone with dibutyryl cyclic AMP induced neurite outgrowth and enhanced electrical excitability but did not lead to protection from 6-hydroxydopamine killing. The morphological response of the SY-5Y cells to dibutyryl cyclic AMP was quite different from that observed after NGF treatment. We propose the SY-5Y clone as a model for the study of the regulation of NGF-induced differentiation in neuronal cells.

    Original languageEnglish (US)
    Pages (from-to)341-355
    Number of pages15
    JournalDevelopmental Biology
    Volume71
    Issue number2
    DOIs
    StatePublished - 1979

    Fingerprint

    Nerve Growth Factor
    Neurons
    Cell Line
    Oxidopamine
    Bucladesine
    Neurites
    Clone Cells
    Sympathetic Ganglia
    Cytoprotection
    Membranes
    Mixed Function Oxygenases
    Diploidy
    Neuroblastoma
    Adrenergic Agents
    Thymidine
    Neurotransmitter Agents
    Dopamine
    Proteins
    Cell Culture Techniques
    Cell Proliferation

    ASJC Scopus subject areas

    • Developmental Biology

    Cite this

    Perez-Polo, J. R., Werrbach-Perez, K., & Tiffany-Castiglioni, E. (1979). A human clonal cell line model of differentiating neurons. Developmental Biology, 71(2), 341-355. https://doi.org/10.1016/0012-1606(79)90174-X

    A human clonal cell line model of differentiating neurons. / Perez-Polo, J. R.; Werrbach-Perez, K.; Tiffany-Castiglioni, E.

    In: Developmental Biology, Vol. 71, No. 2, 1979, p. 341-355.

    Research output: Contribution to journalArticle

    Perez-Polo, JR, Werrbach-Perez, K & Tiffany-Castiglioni, E 1979, 'A human clonal cell line model of differentiating neurons', Developmental Biology, vol. 71, no. 2, pp. 341-355. https://doi.org/10.1016/0012-1606(79)90174-X
    Perez-Polo, J. R. ; Werrbach-Perez, K. ; Tiffany-Castiglioni, E. / A human clonal cell line model of differentiating neurons. In: Developmental Biology. 1979 ; Vol. 71, No. 2. pp. 341-355.
    @article{7e4ab4d7b09a415fabd1babbeb375621,
    title = "A human clonal cell line model of differentiating neurons",
    abstract = "The human neuroblastoma cell line SK-N-SH and its thrice-subcloned derivative, SY-5Y, are nearly diploid cell lines with high levels of dopamine β-hydroxylase, a key enzyme in adrenergic neurotransmitter synthesis. The SY-5Y subclone also displays a neuroblast-like morphology in cell culture and in the undifferentiated state does not have electrically excitable membranes. In this study the response of the SY-5Y cells to the nerve growth factor protein, NGF, is described. After 5 days in culture in the presence of NGF, the SY-5Y cells extended neurites, ceased multiplying, and aggregated into clumps similar to those observed in primary cultures of sympathetic ganglia treated with NGF. Ultrastructural analysis of the induced processes showed them to be neurites. Whereas NGF treatment inhibited the incorporation of [3H]thymidine into DNA and inhibited cellular proliferation, it stimulated incorporation of3H-amino acids into protein. Further analysis of these differentiated cells showed them to have developed electrically excitable membranes. Undifferentiated cells were selectively killed by 6-hydroxydopamine, whereas NGF treatment led to protection of the differentiated cells from 6-hydroxydopamine killing. Treatment of the SY-5Y clone with dibutyryl cyclic AMP induced neurite outgrowth and enhanced electrical excitability but did not lead to protection from 6-hydroxydopamine killing. The morphological response of the SY-5Y cells to dibutyryl cyclic AMP was quite different from that observed after NGF treatment. We propose the SY-5Y clone as a model for the study of the regulation of NGF-induced differentiation in neuronal cells.",
    author = "Perez-Polo, {J. R.} and K. Werrbach-Perez and E. Tiffany-Castiglioni",
    year = "1979",
    doi = "10.1016/0012-1606(79)90174-X",
    language = "English (US)",
    volume = "71",
    pages = "341--355",
    journal = "Developmental Biology",
    issn = "0012-1606",
    publisher = "Academic Press Inc.",
    number = "2",

    }

    TY - JOUR

    T1 - A human clonal cell line model of differentiating neurons

    AU - Perez-Polo, J. R.

    AU - Werrbach-Perez, K.

    AU - Tiffany-Castiglioni, E.

    PY - 1979

    Y1 - 1979

    N2 - The human neuroblastoma cell line SK-N-SH and its thrice-subcloned derivative, SY-5Y, are nearly diploid cell lines with high levels of dopamine β-hydroxylase, a key enzyme in adrenergic neurotransmitter synthesis. The SY-5Y subclone also displays a neuroblast-like morphology in cell culture and in the undifferentiated state does not have electrically excitable membranes. In this study the response of the SY-5Y cells to the nerve growth factor protein, NGF, is described. After 5 days in culture in the presence of NGF, the SY-5Y cells extended neurites, ceased multiplying, and aggregated into clumps similar to those observed in primary cultures of sympathetic ganglia treated with NGF. Ultrastructural analysis of the induced processes showed them to be neurites. Whereas NGF treatment inhibited the incorporation of [3H]thymidine into DNA and inhibited cellular proliferation, it stimulated incorporation of3H-amino acids into protein. Further analysis of these differentiated cells showed them to have developed electrically excitable membranes. Undifferentiated cells were selectively killed by 6-hydroxydopamine, whereas NGF treatment led to protection of the differentiated cells from 6-hydroxydopamine killing. Treatment of the SY-5Y clone with dibutyryl cyclic AMP induced neurite outgrowth and enhanced electrical excitability but did not lead to protection from 6-hydroxydopamine killing. The morphological response of the SY-5Y cells to dibutyryl cyclic AMP was quite different from that observed after NGF treatment. We propose the SY-5Y clone as a model for the study of the regulation of NGF-induced differentiation in neuronal cells.

    AB - The human neuroblastoma cell line SK-N-SH and its thrice-subcloned derivative, SY-5Y, are nearly diploid cell lines with high levels of dopamine β-hydroxylase, a key enzyme in adrenergic neurotransmitter synthesis. The SY-5Y subclone also displays a neuroblast-like morphology in cell culture and in the undifferentiated state does not have electrically excitable membranes. In this study the response of the SY-5Y cells to the nerve growth factor protein, NGF, is described. After 5 days in culture in the presence of NGF, the SY-5Y cells extended neurites, ceased multiplying, and aggregated into clumps similar to those observed in primary cultures of sympathetic ganglia treated with NGF. Ultrastructural analysis of the induced processes showed them to be neurites. Whereas NGF treatment inhibited the incorporation of [3H]thymidine into DNA and inhibited cellular proliferation, it stimulated incorporation of3H-amino acids into protein. Further analysis of these differentiated cells showed them to have developed electrically excitable membranes. Undifferentiated cells were selectively killed by 6-hydroxydopamine, whereas NGF treatment led to protection of the differentiated cells from 6-hydroxydopamine killing. Treatment of the SY-5Y clone with dibutyryl cyclic AMP induced neurite outgrowth and enhanced electrical excitability but did not lead to protection from 6-hydroxydopamine killing. The morphological response of the SY-5Y cells to dibutyryl cyclic AMP was quite different from that observed after NGF treatment. We propose the SY-5Y clone as a model for the study of the regulation of NGF-induced differentiation in neuronal cells.

    UR - http://www.scopus.com/inward/record.url?scp=0018748555&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0018748555&partnerID=8YFLogxK

    U2 - 10.1016/0012-1606(79)90174-X

    DO - 10.1016/0012-1606(79)90174-X

    M3 - Article

    C2 - 499664

    AN - SCOPUS:0018748555

    VL - 71

    SP - 341

    EP - 355

    JO - Developmental Biology

    JF - Developmental Biology

    SN - 0012-1606

    IS - 2

    ER -