title: Ryanodine receptor: a new therapeutic target to control diabetic cardiomyopathy.
abstract: Diabetes mellitus is a major risk factor for cardiovascular complications. Intracellular Ca(2+) release plays an important role in the regulation of muscle contraction. Sarcoplasmic reticulum Ca(2+) release is controlled by dedicated molecular machinery, composed of a complex of cardiac ryanodine receptors (RyR2s). Acquired and genetic defects in this complex result in a spectrum of abnormal Ca(2+) release phenotypes in heart. Cardiovascular dysfunction is a leading cause for mortality of diabetic individuals due, in part, to a specific cardiomyopathy, and to altered vascular reactivity. Cardiovascular complications result from multiple parameters, including glucotoxicity, lipotoxicity, fibrosis, and mitochondrial uncoupling. In diabetic subjects, oxidative stress arises from an imbalance between production of reactive oxygen and nitrogen species and capability of the system to readily detoxify reactive intermediates. To date, the etiology underlying diabetes-induced reductions in myocyte and cardiac contractility remains incompletely understood. However, numerous studies, including work from our laboratory, suggest that these defects stem in part from perturbation in intracellular Ca(2+) cycling. Since the RyR2s are one of the well-characterized redox-sensitive ion channels in heart, this article summarizes recent findings on redox regulation of cardiac Ca(2+) transport systems and discusses contributions of redox regulation to pathological cardiac function in diabetes.
authors.affiliation: Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey . belma.turan@medicine.ankara.edu.tr
authors.forename: Belma
authors.initials: B
authors.lastname: Turan
authors.forename: Guy
authors.initials: G
authors.lastname: Vassort
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D020013:Calcium Signaling / Q000187:drug effects; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D018384:Oxidative Stress; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D055550:Protein Stability; D012084:Renin-Angiotensin System; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013841:Thiazepines / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D002121:Calcium Channel Blockers; D047428:Protein Kinase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D013841:Thiazepines; C109183:K201 compound; D004958:Estradiol