title: Reductive potential - a savior turns stressor in protein aggregation cardiomyopathy.
abstract: Redox homeostasis is essential for basal signaling of several physiological processes, but a unilateral shift towards an 'oxidative' or 'reductive' trait will alter intracellular redox milieu. Typically, such an event influences the structure and the native function of a cell or an organelle. Numerous experimental research and clinical trials over the last 6 decades have demonstrated that enhanced oxygen-derived free radicals constitute a major stimulus to trigger damage in several human diseases, including cardiovascular complications supporting the theory of oxidative stress (OS). However, until our key discovery, the dynamic interrelationship between "Reductive Stress (RS)" and cardiac health has been obscured by overwhelming OS studies (Rajasekaran et al., 2007). Notably, this seminal finding spurred considerable interest in investigations of other mechanistic insights, and thus far the results indicate a similar or stronger role for RS, as that of OS. In addition, from our own findings we strongly believe that constitutive activation of pathways that enable sustained generation of reducing equivalents of glutathione (GSH), reduced nicotinamide adenine dinucleotide phosphate (NADPH) will cause RS and impair the basal cellular signaling mechanisms operating through harmless pro-oxidative events, in turn, disrupting single and/or a combination of key cellular processes such as growth, maturation, differentiation, survival, death etc., that govern healthy cell physiology. Here, we have discussed the role of RS as a causal or contributing factor in relevant pathophysiology of a major cardiac disease of human origin.
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, United States.
authors.forename: Madhusudhanan
authors.initials: M
authors.lastname: Narasimhan
authors.affiliation: Cardiac Aging & Redox Signaling Laboratory, Division of Molecular & Cellular Pathology, Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294-2180, United States; Center for Free Radical Biology, The University of Alabama at Birmingham, Birmingham, AL 35294-2180, United States; Division of Cardiovascular Medicine, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, United States. Electronic address: rajnsr@uab.edu.
authors.forename: Namakkal S
authors.initials: NS
authors.lastname: Rajasekaran
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D009124:Muscle Proteins
keywords: Cardiomyopathy; GSH; Nrf2; Protein aggregation; Reductive stress; hR120GCryAB