Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells

Skeletal muscle differentiation involves myoblast alignment, elongation, and fusion into multinucleate myotubes, together with the induction of regulatory and structural muscle-specific genes. Here we show that two phosphatidylinositol 3-kinase inhibitors, LY294002 and wortmannin, blocked an essenti...

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Detalles Bibliográficos
Autores: Kaliman, Perla, Viñals Canals, Francesc, Testar, Xavier, Palacín Prieto, Manuel, Zorzano Olarte, Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:1996
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/177606
Acceso en línea:https://hdl.handle.net/2445/177606
Access Level:acceso abierto
Palabra clave:Diferenciació cel·lular
Inhibidors enzimàtics
Músculs
Proteïnes
Cell diferentiation
Enzyme inhibitors
Muscles
Proteins
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spelling Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cellsKaliman, PerlaViñals Canals, FrancescTestar, XavierPalacín Prieto, ManuelZorzano Olarte, AntonioDiferenciació cel·lularInhibidors enzimàticsMúsculsProteïnesCell diferentiationEnzyme inhibitorsMusclesProteinsSkeletal muscle differentiation involves myoblast alignment, elongation, and fusion into multinucleate myotubes, together with the induction of regulatory and structural muscle-specific genes. Here we show that two phosphatidylinositol 3-kinase inhibitors, LY294002 and wortmannin, blocked an essential step in the differentiation of two skeletal muscle cell models. Both inhibitors abolished the capacity of L6E9 myoblasts to form myotubes, without affecting myoblast proliferation, elongation, or alignment. Myogenic events like the induction of myogenin and of glucose carrier GLUT4 were also blocked and myoblasts could not exit the cell cycle, as measured by the lack of mRNA induction of p21 cyclin-dependent kinase inhibitor. Overexpresssion of MyoD in 10T1/2 cells was not sufficient to bypass the myogenic differentiation blockade by LY294002. Upon serum withdrawal, 10T1/2-MyoD cells formed myotubes and showed increased levels of myogenin and p21. In contrast, LY294002-treated cells exhibited none of these myogenic characteristics and maintained high levels of Id, a negative regulator of myogenesis. These data indicate that whereas phosphatidylinositol 3-kinase is not indispensable for cell proliferation or in the initial events of myoblast differentiation, i.e. elongation and alignment, it appears to be essential for terminal differentiation of muscle cells.American Society for Biochemistry and Molecular Biology2021202119962021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion6 p.application/pdfhttps://hdl.handle.net/2445/177606Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1074/jbc.271.32.19146Journal of Biological Chemistry, 1996, vol. 271, num. 32, p. 19146-19151https://doi.org/10.1074/jbc.271.32.19146(c) American Society for Biochemistry and Molecular Biology, 1996info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1776062026-05-29T05:05:01Z
dc.title.none.fl_str_mv Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells
title Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells
spellingShingle Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells
Kaliman, Perla
Diferenciació cel·lular
Inhibidors enzimàtics
Músculs
Proteïnes
Cell diferentiation
Enzyme inhibitors
Muscles
Proteins
title_short Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells
title_full Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells
title_fullStr Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells
title_full_unstemmed Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells
title_sort Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells
dc.creator.none.fl_str_mv Kaliman, Perla
Viñals Canals, Francesc
Testar, Xavier
Palacín Prieto, Manuel
Zorzano Olarte, Antonio
author Kaliman, Perla
author_facet Kaliman, Perla
Viñals Canals, Francesc
Testar, Xavier
Palacín Prieto, Manuel
Zorzano Olarte, Antonio
author_role author
author2 Viñals Canals, Francesc
Testar, Xavier
Palacín Prieto, Manuel
Zorzano Olarte, Antonio
author2_role author
author
author
author
dc.subject.none.fl_str_mv Diferenciació cel·lular
Inhibidors enzimàtics
Músculs
Proteïnes
Cell diferentiation
Enzyme inhibitors
Muscles
Proteins
topic Diferenciació cel·lular
Inhibidors enzimàtics
Músculs
Proteïnes
Cell diferentiation
Enzyme inhibitors
Muscles
Proteins
description Skeletal muscle differentiation involves myoblast alignment, elongation, and fusion into multinucleate myotubes, together with the induction of regulatory and structural muscle-specific genes. Here we show that two phosphatidylinositol 3-kinase inhibitors, LY294002 and wortmannin, blocked an essential step in the differentiation of two skeletal muscle cell models. Both inhibitors abolished the capacity of L6E9 myoblasts to form myotubes, without affecting myoblast proliferation, elongation, or alignment. Myogenic events like the induction of myogenin and of glucose carrier GLUT4 were also blocked and myoblasts could not exit the cell cycle, as measured by the lack of mRNA induction of p21 cyclin-dependent kinase inhibitor. Overexpresssion of MyoD in 10T1/2 cells was not sufficient to bypass the myogenic differentiation blockade by LY294002. Upon serum withdrawal, 10T1/2-MyoD cells formed myotubes and showed increased levels of myogenin and p21. In contrast, LY294002-treated cells exhibited none of these myogenic characteristics and maintained high levels of Id, a negative regulator of myogenesis. These data indicate that whereas phosphatidylinositol 3-kinase is not indispensable for cell proliferation or in the initial events of myoblast differentiation, i.e. elongation and alignment, it appears to be essential for terminal differentiation of muscle cells.
publishDate 1996
dc.date.none.fl_str_mv 1996
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177606
url https://hdl.handle.net/2445/177606
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1074/jbc.271.32.19146
Journal of Biological Chemistry, 1996, vol. 271, num. 32, p. 19146-19151
https://doi.org/10.1074/jbc.271.32.19146
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 1996
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 1996
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 6 p.
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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