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StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation

Recent studies have demonstrated that human stearoylCoA desaturase-1 (SCD1), a Δ9-desaturase that converts saturated fatty acids (SFA) into monounsaturated fatty acids, controls the rate of lipogenesis, cell proliferation and tumorigenic capacity in cancer cells. However, the biological function of...

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Autores principales: Sinner, Debora I., Kim, Gretchun J., Henderson, Gregory C., Igal, R. Ariel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382174/
https://www.ncbi.nlm.nih.gov/pubmed/22745828
http://dx.doi.org/10.1371/journal.pone.0039787
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author Sinner, Debora I.
Kim, Gretchun J.
Henderson, Gregory C.
Igal, R. Ariel
author_facet Sinner, Debora I.
Kim, Gretchun J.
Henderson, Gregory C.
Igal, R. Ariel
author_sort Sinner, Debora I.
collection PubMed
description Recent studies have demonstrated that human stearoylCoA desaturase-1 (SCD1), a Δ9-desaturase that converts saturated fatty acids (SFA) into monounsaturated fatty acids, controls the rate of lipogenesis, cell proliferation and tumorigenic capacity in cancer cells. However, the biological function of stearoylCoA desaturase-5 (SCD5), a second isoform of human SCD that is highly expressed in brain, as well as its potential role in human disease, remains unknown. In this study we report that the constitutive overexpression of human SCD5 in mouse Neuro2a cells, a widely used cell model of neuronal growth and differentiation, displayed a greater n-7 MUFA-to-SFA ratio in cell lipids compared to empty-vector transfected cells (controls). De novo synthesis of phosphatidylcholine and cholesterolesters was increased whereas phosphatidylethanolamine and triacylglycerol formation was reduced in SCD5-expressing cells with respect to their controls, suggesting a differential use of SCD5 products for lipogenic reactions. We also observed that SCD5 expression markedly accelerated the rate of cell proliferation and suppressed the induction of neurite outgrowth, a typical marker of neuronal differentiation, by retinoic acid indicating that the desaturase plays a key role in the mechanisms of cell division and differentiation. Critical signal transduction pathways that are known to modulate these processes, such epidermal growth factor receptor (EGFR)Akt/ERK and Wnt, were affected by SCD5 expression. Epidermal growth factor-induced phosphorylation of EGFR, Akt and ERK was markedly blunted in SCD5-expressing cells. Furthermore, the activity of canonical Wnt was reduced whereas the non-canonical Wnt was increased by the presence of SCD5 activity. Finally, SCD5 expression increased the secretion of recombinant Wnt5a, a non-canonical Wnt, whereas it reduced the cellular and secreted levels of canonical Wnt7b. Our data suggest that, by a coordinated modulation of key lipogenic pathways and transduction signaling cascades, SCD5 participates in the regulation of neuronal cell growth and differentiation.
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spelling pubmed-33821742012-06-28 StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation Sinner, Debora I. Kim, Gretchun J. Henderson, Gregory C. Igal, R. Ariel PLoS One Research Article Recent studies have demonstrated that human stearoylCoA desaturase-1 (SCD1), a Δ9-desaturase that converts saturated fatty acids (SFA) into monounsaturated fatty acids, controls the rate of lipogenesis, cell proliferation and tumorigenic capacity in cancer cells. However, the biological function of stearoylCoA desaturase-5 (SCD5), a second isoform of human SCD that is highly expressed in brain, as well as its potential role in human disease, remains unknown. In this study we report that the constitutive overexpression of human SCD5 in mouse Neuro2a cells, a widely used cell model of neuronal growth and differentiation, displayed a greater n-7 MUFA-to-SFA ratio in cell lipids compared to empty-vector transfected cells (controls). De novo synthesis of phosphatidylcholine and cholesterolesters was increased whereas phosphatidylethanolamine and triacylglycerol formation was reduced in SCD5-expressing cells with respect to their controls, suggesting a differential use of SCD5 products for lipogenic reactions. We also observed that SCD5 expression markedly accelerated the rate of cell proliferation and suppressed the induction of neurite outgrowth, a typical marker of neuronal differentiation, by retinoic acid indicating that the desaturase plays a key role in the mechanisms of cell division and differentiation. Critical signal transduction pathways that are known to modulate these processes, such epidermal growth factor receptor (EGFR)Akt/ERK and Wnt, were affected by SCD5 expression. Epidermal growth factor-induced phosphorylation of EGFR, Akt and ERK was markedly blunted in SCD5-expressing cells. Furthermore, the activity of canonical Wnt was reduced whereas the non-canonical Wnt was increased by the presence of SCD5 activity. Finally, SCD5 expression increased the secretion of recombinant Wnt5a, a non-canonical Wnt, whereas it reduced the cellular and secreted levels of canonical Wnt7b. Our data suggest that, by a coordinated modulation of key lipogenic pathways and transduction signaling cascades, SCD5 participates in the regulation of neuronal cell growth and differentiation. Public Library of Science 2012-06-22 /pmc/articles/PMC3382174/ /pubmed/22745828 http://dx.doi.org/10.1371/journal.pone.0039787 Text en Sinner et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sinner, Debora I.
Kim, Gretchun J.
Henderson, Gregory C.
Igal, R. Ariel
StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation
title StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation
title_full StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation
title_fullStr StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation
title_full_unstemmed StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation
title_short StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation
title_sort stearoylcoa desaturase-5: a novel regulator of neuronal cell proliferation and differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382174/
https://www.ncbi.nlm.nih.gov/pubmed/22745828
http://dx.doi.org/10.1371/journal.pone.0039787
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