title: Luteolin improves cardiac dysfunction in heart failure rats by regulating sarcoplasmic reticulum Ca2+-ATPase 2a.
abstract: We previously found that luteolin (Lut) appeared to improve the contractility of cardiomyocytes during ischemia/reperfusion in rats. The enhancement was associated with the alteration in sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a). This finding prompted us to consider if the mechanism worked in heart failure (HF). We studied the regulation of SERCA2a by Lut in failing cardiomyocytes and intact heart of rats. Improvement of contractility and the mechanisms centered on SERCA2a were studied in isolated cardiomyocytes and intact heart. We found that Lut significantly improved contractility and Ca2+transients, ameliorated expression, activity and stability of SERCA2a and upregulated expression of small ubiquitin-related modifier (SUMO) 1, which is a newfound SERCA2a regulator. Lut also increased phosphorylation of protein kinase B (Akt), phospholaban (PLB) and sumoylation of SERCA2a, specificity protein 1 (Sp1). Transcriptions of SUMO1 and SERCA2a were concurrently increased. Inhibition of posphatidylinositol 3 kinase/Akt (PI3K/Akt) pathway and SERCA2a activity both markedly abolished Lut-induced benefits in vitro and in vivo. Lut upregulated the expression ratio of Bcl-2/Bax, caspase-3/cleaved-Caspase3. Meanwhile, Lut ameliorated the myocardium fibrosis of HF. These discoveries provide an important potential therapeutic strategy that Lut targeted SERCA2a SUMOylation related to PI3K/Akt-mediated regulations on rescuing the dysfunction of HF.
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China.
authors.forename: Tongda
authors.initials: T
authors.lastname: Xu
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wu
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Defeng
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Buchun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy*; D047311:Luteolin / Q000008:administration & dosage* / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: D002317:Cardiovascular Agents; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D047311:Luteolin