title: Polydatin protects cardiac function against burn injury by inhibiting sarcoplasmic reticulum Ca2+ leak by reducing oxidative modification of ryanodine receptors.
abstract: Our recent studies demonstrate that burn trauma induces leaky sarcoplasmic reticulum (SR) in heart due to excessively active ryanodine receptor (RyR) function. SR Ca(2+) leak causes partial depletion of SR Ca(2+) content and disturbances in intracellular Ca(2+) homeostasis, resulting in the pathogenesis of burn-generated cardiac dysfunction. This study investigated the role of polydatin, a resveratrol glucoside, in preventing SR leak and its therapeutic effect against burn-generated cardiac dysfunction. We found that polydatin treatment improved cardiac function impaired by burn injury of 30% of total body surface area. Parallel to the alterations in cardiac function, polydatin significantly increased the defective systolic Ca(2+) transient and contractility in burn-traumatized cardiomyocytes. Burn injury increased the occurrence of Ca(2+) sparks. The enhancement of Ca(2+) spark-mediated SR leak caused partial depletion of SR Ca(2+) content in burn-traumatized cardiomyocytes. Furthermore, we found that the content of free thiols (the number of reduced cysteines) in RyR2 in cardiomyocytes determined by the monobromobimane fluorescence of RyR2 was decreased markedly in burn-traumatized hearts. Polydatin treatment decreased intracellular reactive oxygen species levels and restored the amount of free thiols in RyR2 in burns. Concomitantly, polydatin corrected Ca(2+) spark-mediated SR leak and restored SR Ca(2+) load. The systolic Ca(2+) transient and cellular contractility were significantly increased by polydatin treatment. Taken together, the present findings provide the first evidence demonstrating that polydatin prevents enhanced Ca(2+) spark-mediated SR leak by reducing oxidative stress in RyR2 in burn-traumatized heart, leading to protection of cardiac function against burn injury.
authors.affiliation: Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Liu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Deng
authors.forename: Liqin
authors.initials: L
authors.lastname: Lan
authors.forename: Xiang
authors.initials: X
authors.lastname: Xue
authors.forename: Cuicui
authors.initials: C
authors.lastname: Zhang
authors.forename: Gaorui
authors.initials: G
authors.lastname: Cai
authors.forename: Xinping
authors.initials: X
authors.lastname: Luo
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002056:Burns / Q000188:drug therapy / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D005960:Glucosides / Q000008:administration & dosage*; D006335:Heart Injuries / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D005960:Glucosides; D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel; D013267:Stilbenes; D002118:Calcium; C058229:polydatin