title: The cardiac L-type calcium channel alpha subunit is a target for direct redox modification during oxidative stress-the role of cysteine residues in the alpha interacting domain.
abstract: Cardiovascular disease is the leading cause of death in the Western world. The incidence of cardiovascular disease is predicted to further rise with the increase in obesity and diabetes and with the aging population. Even though the survival rate from ischaemic heart disease has improved over the past 30 years, many patients progress to a chronic pathological condition, known as cardiac hypertrophy that is associated with an increase in morbidity and mortality. Reactive oxygen species (ROS) and calcium play an essential role in mediating cardiac hypertrophy. The L-type calcium channel is the main route for calcium influx into cardiac myocytes. There is now good evidence for a direct role for the L-type calcium channel in the development of cardiac hypertrophy. Cysteines on the channel are targets for redox modification and glutathionylation of the channel can modulate the function of the channel protein leading to the onset of pathology. The cysteine responsible for modification of L-type calcium channel function has now been identified. Detailed understanding of the role of cysteines as possible targets during oxidative stress may assist in designing therapy to prevent the development of hypertrophy and heart failure.
authors.affiliation: School of Anatomy, Physiology and Human Biology, University of Western Australia, Crawley, WA, Australia.
authors.forename: Padmapriya
authors.initials: P
authors.lastname: Muralidharan
authors.affiliation: School of Anatomy, Physiology and Human Biology, University of Western Australia, Crawley, WA, Australia.
authors.forename: Henrietta
authors.identifier: 0000-0003-0063-257X
authors.initials: H
authors.lastname: Cserne Szappanos
authors.affiliation: Harry Perkins Institute of Medical Research and Centre for Medical Research, University of Western Australia, Perth, WA, Australia.|School of Veterinary and Life Sciences, Murdoch University, Murdoch, WA, Australia.
authors.forename: Evan
authors.initials: E
authors.lastname: Ingley
authors.affiliation: School of Anatomy, Physiology and Human Biology, University of Western Australia, Crawley, WA, Australia.|Victor Chang Cardiac Research Institute, Sydney, NSW, Australia.
authors.forename: Livia C
authors.initials: LC
authors.lastname: Hool
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D006332:Cardiomegaly / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D003545:Cysteine; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020257:Ventricular Remodeling
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D017382:Reactive Oxygen Species; D003545:Cysteine
keywords: Cav1.2 protein; L-type calcium channel; cysteine; glutathionylation; heart; hypertrophy; oxidative stress; structure-function relationship