Glutathionylation of the L-type Ca2+ Channel in Oxidative Stress-Induced Pathology of the Heart

    Research output: Contribution to journalReview article

    7 Citations (Scopus)

    Abstract

    There is mounting evidence to suggest that protein glutathionylation is a key process contributing to the development of pathology. Glutathionylation occurs as a result of posttranslational modification of a protein and involves the addition of a glutathione moiety at cysteine residues. Such modification can occur on a number of proteins, and exerts a variety of functional consequences. The L-type Ca2+ channel has been identified as a glutathionylation target that participates in the development of cardiac pathology. Ca2+ influx via the L-type Ca2+ channel increases production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes during periods of oxidative stress. This induces a persistent increase in channel open probability, and the resulting constitutive increase in Ca2+ influx amplifies the cross-talk between the mitochondria and the channel. Novel strategies utilising targeted peptide delivery to uncouple mitochondrial ROS and Ca2+ flux via the L-type Ca2+ channel following ischemia-reperfusion have delivered promising results, and have proven capable of restoring appropriate mitochondrial function in myocytes and in vivo.
    Original languageEnglish
    Pages (from-to)19203-19225
    JournalInternation Journal of Molecular Sciences
    Volume15
    Issue number10
    DOIs
    Publication statusPublished - 22 Oct 2014

    Fingerprint

    Oxidative stress
    pathology
    Pathology
    Oxidative Stress
    Proteins
    Reactive Oxygen Species
    Mitochondria
    proteins
    Oxygen
    Post Translational Protein Processing
    Mountings
    Cardiac Myocytes
    Muscle Cells
    Peptides
    Reperfusion
    Glutathione
    Cysteine
    Ischemia
    ischemia
    muscle cells

    Cite this

    @article{4b4c611de77d4abdbf07e9ac24102627,
    title = "Glutathionylation of the L-type Ca2+ Channel in Oxidative Stress-Induced Pathology of the Heart",
    abstract = "There is mounting evidence to suggest that protein glutathionylation is a key process contributing to the development of pathology. Glutathionylation occurs as a result of posttranslational modification of a protein and involves the addition of a glutathione moiety at cysteine residues. Such modification can occur on a number of proteins, and exerts a variety of functional consequences. The L-type Ca2+ channel has been identified as a glutathionylation target that participates in the development of cardiac pathology. Ca2+ influx via the L-type Ca2+ channel increases production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes during periods of oxidative stress. This induces a persistent increase in channel open probability, and the resulting constitutive increase in Ca2+ influx amplifies the cross-talk between the mitochondria and the channel. Novel strategies utilising targeted peptide delivery to uncouple mitochondrial ROS and Ca2+ flux via the L-type Ca2+ channel following ischemia-reperfusion have delivered promising results, and have proven capable of restoring appropriate mitochondrial function in myocytes and in vivo.",
    author = "Vicky Johnstone and Livia Hool",
    year = "2014",
    month = "10",
    day = "22",
    doi = "10.3390/ijms151019203",
    language = "English",
    volume = "15",
    pages = "19203--19225",
    journal = "Internation Journal of Molecular Sciences",
    issn = "1422-0067",
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    Glutathionylation of the L-type Ca2+ Channel in Oxidative Stress-Induced Pathology of the Heart. / Johnstone, Vicky; Hool, Livia.

    In: Internation Journal of Molecular Sciences, Vol. 15, No. 10, 22.10.2014, p. 19203-19225.

    Research output: Contribution to journalReview article

    TY - JOUR

    T1 - Glutathionylation of the L-type Ca2+ Channel in Oxidative Stress-Induced Pathology of the Heart

    AU - Johnstone, Vicky

    AU - Hool, Livia

    PY - 2014/10/22

    Y1 - 2014/10/22

    N2 - There is mounting evidence to suggest that protein glutathionylation is a key process contributing to the development of pathology. Glutathionylation occurs as a result of posttranslational modification of a protein and involves the addition of a glutathione moiety at cysteine residues. Such modification can occur on a number of proteins, and exerts a variety of functional consequences. The L-type Ca2+ channel has been identified as a glutathionylation target that participates in the development of cardiac pathology. Ca2+ influx via the L-type Ca2+ channel increases production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes during periods of oxidative stress. This induces a persistent increase in channel open probability, and the resulting constitutive increase in Ca2+ influx amplifies the cross-talk between the mitochondria and the channel. Novel strategies utilising targeted peptide delivery to uncouple mitochondrial ROS and Ca2+ flux via the L-type Ca2+ channel following ischemia-reperfusion have delivered promising results, and have proven capable of restoring appropriate mitochondrial function in myocytes and in vivo.

    AB - There is mounting evidence to suggest that protein glutathionylation is a key process contributing to the development of pathology. Glutathionylation occurs as a result of posttranslational modification of a protein and involves the addition of a glutathione moiety at cysteine residues. Such modification can occur on a number of proteins, and exerts a variety of functional consequences. The L-type Ca2+ channel has been identified as a glutathionylation target that participates in the development of cardiac pathology. Ca2+ influx via the L-type Ca2+ channel increases production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes during periods of oxidative stress. This induces a persistent increase in channel open probability, and the resulting constitutive increase in Ca2+ influx amplifies the cross-talk between the mitochondria and the channel. Novel strategies utilising targeted peptide delivery to uncouple mitochondrial ROS and Ca2+ flux via the L-type Ca2+ channel following ischemia-reperfusion have delivered promising results, and have proven capable of restoring appropriate mitochondrial function in myocytes and in vivo.

    U2 - 10.3390/ijms151019203

    DO - 10.3390/ijms151019203

    M3 - Review article

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    SP - 19203

    EP - 19225

    JO - Internation Journal of Molecular Sciences

    JF - Internation Journal of Molecular Sciences

    SN - 1422-0067

    IS - 10

    ER -