Cholesterol oxides mediated changes in cytoskeletal organisation involves Rho GTPases

Henrique Girão, Paulo Pereira, José Ramalho, Roy Quinlan, Alan Prescott (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    The small GTPases Rho, Rac, and Cdc42 regulate the actin cytoskeleton in all eukaryotic cells. In this study we have evaluated the effect of cholesterol oxides (7-ketocholesterol and 25-hydroxycholesterol) on cell migration, cell adhesion, and cytoskeletal organisation of lens epithelial cells (LEC). Effects of cholesterol oxides on cytoskeleton were evaluated by immunofluorescence confocal microscopy. The 7-ketocholesterol induced cell arborisation, with bundling of vimentin and tubulin in the cell processes and formation of filopodia and stress fibres. Cells treated with 25-hydroxycholesterol showed a collapse of vimentin filaments towards the nucleus and formation of lamellipodia. In addition, cells treated with 7-ketocholesterol or 25-hydroxycholesterol showed decreased migration. The effects of cholesterol oxides on cytoskeletal proteins involve the activation of the small GTPases Rho, Rac, and Cdc42. Indeed, formation of both filopodia and stress fibres induced by 7-ketocholesterol is inhibited by overexpressing dominant negatives forms of Cdc42 and RhoA, respectively. Similarly, the collapse of vimentin intermediate filament network and the formation of lamellipodia, induced by 25-hydroxycholesterol, is inhibited by overexpressing dominant negatives forms of Rac1. The effects of cholesterol oxides described in this study for LEC are also observed for at least two other cell lines (H36CE and U373), suggesting that this may represent a general mechanism whereby cholesterol oxides induces cytoskeletal disorganisation.

    Original languageEnglish
    Pages (from-to)502-513
    Number of pages12
    JournalExperimental Cell Research
    Volume291
    Issue number2
    DOIs
    Publication statusPublished - 1 Dec 2003

    Fingerprint

    rho GTP-Binding Proteins
    Pseudopodia
    Oxides
    Cholesterol
    Vimentin
    Stress Fibers
    Monomeric GTP-Binding Proteins
    Lenses
    Epithelial Cells
    Cytoskeletal Proteins
    Intermediate Filaments
    Eukaryotic Cells
    Tubulin
    Cytoskeleton
    Actin Cytoskeleton
    Fluorescence Microscopy
    Cell Adhesion
    Confocal Microscopy
    Cell Movement
    Cell Line

    Keywords

    • Cell-cell adhesion
    • Cholesterol oxides
    • Cytoskeleton
    • Lens
    • Migration
    • Rho GTPases

    Cite this

    Girão, Henrique ; Pereira, Paulo ; Ramalho, José ; Quinlan, Roy ; Prescott, Alan. / Cholesterol oxides mediated changes in cytoskeletal organisation involves Rho GTPases. In: Experimental Cell Research. 2003 ; Vol. 291, No. 2. pp. 502-513.
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    Cholesterol oxides mediated changes in cytoskeletal organisation involves Rho GTPases. / Girão, Henrique; Pereira, Paulo; Ramalho, José; Quinlan, Roy; Prescott, Alan (Lead / Corresponding author).

    In: Experimental Cell Research, Vol. 291, No. 2, 01.12.2003, p. 502-513.

    Research output: Contribution to journalArticle

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