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.
authors.affiliation: School of Anatomy, Physiology and Human Biology, the University of Western Australia, Crawley 6009, WA, Australia. vicky.johnstone@uwa.edu.au.
authors.forename: Victoria P A
authors.initials: VP
authors.lastname: Johnstone
authors.affiliation: School of Anatomy, Physiology and Human Biology, the University of Western Australia, Crawley 6009, WA, Australia. livia.hool@uwa.edu.au.
authors.forename: Livia C
authors.initials: LC
authors.lastname: Hool
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D017382:Reactive Oxygen Species; D005978:Glutathione