title: Resuscitation of a dead cardiomyocyte.
abstract: Although cardiac resuscitation can revive the whole body, the mechanisms are unclear. To this end, we propose that reviving a dead/dysfunctional cardiomyocyte will shed light on resuscitation mechanisms and pave the way to treat cardiac myopathies. The degradation of the myocyte cytoskeleton by the proteasome system which involves calpains, ubiquitin, caspases and matrix metalloproteases is the main focus of this review. The activation of calpains beyond the calpastatin-mediated inhibition due to extensive calcium harbor can lead to titin degradation, damage to the sarcomere and contractile dysfunction. The ubiquitin proteasome system can disturb the protein homeostasis within the cell and generate a dysfunctional myocyte. The matrix metalloproteases disrupt the collagen/elastin ratio and connexins to generate arrhythmias. The concept of cardiac resuscitation stems from protecting the myocyte cytoskeleton and keeping the protein homeostasis intact through management of the degradation machinery. In this regard, proteasome inhibitors for the degradation machinery have an elegant space. Recently exosomes have been identified potentially, as carriers of microRNAs or proteins that can modify the target cells. Exosomes loaded with the inhibitor "cargo" which comprises microRNAs, siRNAs or proteins to inhibit the degradation machinery can be a method of choice for cardiac resuscitation-a process difficult to execute.
authors: Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, Louisville, KY, 40202, USA.
authors: George H
authors: GH
authors: Kunkel
authors: Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, Louisville, KY, 40202, USA. p0chat03@louisville.edu.
authors: Pankaj
authors: P
authors: Chaturvedi
authors: Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, Louisville, KY, 40202, USA.
authors: Suresh C
authors: SC
authors: Tyagi
mesh_terms: D017209:Apoptosis; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012151:Resuscitation; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D006710:Homocysteine; D046988:Proteasome Endopeptidase Complex
keywords: Calpains; Cardiomyocytes; Homocysteine; Proteases; Resuscitation; Ubiquitin