title: Antioxidant effects of hydrogen sulfide on left ventricular remodeling in smoking rats are mediated via PI3K/Akt-dependent activation of Nrf2.
abstract: There is growing evidence that oxidative stress plays critical roles in the pathogenesis of cardiac remodeling. In the present study, we established a rat model of passive smoking and investigated the antioxidant effects of hydrogen sulfide (H2S) on smoking-induced left ventricular remodeling. Cardiac structure and function were evaluated using 2-dimensional echocardiography. Myocardial fibrosis was detected by Masson's trichrome staining and immunohistochemistry. Oxidative stress was assessed by measuring malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities, and reactive oxygen species generation in the myocardium. Neonatal rat cardiomyocytes transfected with specific siRNA and exposed to cigarette smoke condensate and H2S donor sodium hydrosulfide were used to confirm the involvement of Nrf2 and PI3K/Akt signaling in the antioxidant effects of H2S. Our results indicated that H2S could protect against left ventricular remodeling in smoking rats via attenuation of oxidative stress. Moreover, H2S was also found to increase the phosphorylation of Akt and GSK3β and decrease the nuclear expression of Fyn, which consequently leads to nuclear translocation of Nrf2 and elevated expression of HO-1 and NQO1. In conclusion, H2S may exert antioxidant effects on left ventricular remodeling in smoking rats via PI3K/Akt-dependent activation of Nrf2 signaling.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China zhou-xiang@suda.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Liangping
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Jinning
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
authors.forename: Jianchang
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D019610:Cytoprotection; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005355:Fibrosis; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014162:Transfection; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012906:Smoke; D013440:Sulfides; D014028:Tobacco Smoke Pollution; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
keywords: Nrf2; PI3K/Akt; hydrogen sulfide; left ventricular remodeling; oxidative stress; smoking