Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/18603
Title: Cholesterol depletion by methyl-β-cyclodextrin enhances cell proliferation and increases the number of desmin-positive cells in myoblast cultures
Authors: Portilho, Débora M.
Soares, Carolina P.
Morrot, Alexandre
Thiago, Leandro S.
Butler-Browne, Gillian
Savino, Wilson
Costa, Manoel L.
Mermelstein, Cláudia
Affilliation: Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Diferenciação Muscular e Citoesqueleto. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil / Université Paris 6. Institut de Myologie. Thérapie des Maladies du Muscle Strié. Paris, France.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Diferenciação Muscular e Citoesqueleto. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunologia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Puericultura e Pediatria Martagão Gesteira. Núcleo Interdisciplinar de Investigação em Saúde da Criança e do Adolescente. Rio de Janeiro, RJ, Brasil.
Université Paris 6. Institut de Myologie. Thérapie des Maladies du Muscle Strié. Paris, France
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Diferenciação Muscular e Citoesqueleto. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Diferenciação Muscular e Citoesqueleto. Rio de Janeiro, RJ, Brasil.
Abstract: Skeletal myogenesis comprises myoblast replication and differentiation into striated multinucleated myotubes. Agents that interfere with myoblast replication are important tools for the understanding of myogenesis. Recently, we showed that cholesterol depletion by methyl-β-cyclodextrin (MCD) enhances the differentiation step in chick-cultured myogenic cells, involving the activation of the Wnt/β-catenin signaling pathway. However, the effects of cholesterol depletion on myoblast replication have not been carefully studied. Here we show that MCD treatment increases cell proliferation in primary chick myogenic cell cultures. Treatment of myogenic cells with the anti-mitotic reagent cytosine arabinoside, immediately following cholesterol depletion, blocks the MCD-induced effects on proliferation. Cholesterol depletion induced an increase in the number of desmin-positive mononucleated cells, and an increase in desmin expression. MCD induces an increase in the expression of the cell cycle regulator p53 and the master switch gene MyoD1. Treatment with BIO, a specific inhibitor of GSK3β, induced effects similar to MCD on cell proliferation; while treatment with Dkk1, a specific inhibitor of the Wnt/β-catenin pathway, neutralized the effects of MCD. These findings indicate that rapid changes in the cholesterol content in cell membranes of myoblasts can induce cell proliferation, possibly by the activation of the Wnt/β-catenin signaling pathway.
Keywords: Methyl-B-cyclodextrin
Myogenesis
Cholesterol
Cell replication
Desmin
Muscle differentiation
keywords: Metil-B-ciclodextrina
Colesterol
Replicação de células
Desmin
Diferenciação muscular
Desenvolvimento Muscular 
DeCS: Desenvolvimento Muscular 
Issue Date: 2012
Publisher: Elsevier
Citation: PORTILHO, Débora M. et al. Cholesterol depletion by methyl-β-cyclodextrin enhances cell proliferation and increases the number of desmin-positive cells in myoblast cultures. European Journal of Pharmacology, n.694, p.1-12, 2012.
DOI: 10.1016/j.ejphar.2012.07.035
ISSN: 0014-2999
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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