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Glutathionylation of the L-type Ca(2+) Channel in Oxidative Stress-Induced Pathology of the Heart

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 modific...

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Detalles Bibliográficos
Autores principales: Johnstone, Victoria P. A., Hool, Livia C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227269/
https://www.ncbi.nlm.nih.gov/pubmed/25340983
http://dx.doi.org/10.3390/ijms151019203
Descripción
Sumario: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 Ca(2+) channel has been identified as a glutathionylation target that participates in the development of cardiac pathology. Ca(2+) influx via the L-type Ca(2+) 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 Ca(2+) influx amplifies the cross-talk between the mitochondria and the channel. Novel strategies utilising targeted peptide delivery to uncouple mitochondrial ROS and Ca(2+) flux via the L-type Ca(2+) channel following ischemia-reperfusion have delivered promising results, and have proven capable of restoring appropriate mitochondrial function in myocytes and in vivo.