title: Association of cardiac injury with iron-increased oxidative and nitrative modifications of the SERCA2a isoform of sarcoplasmic reticulum Ca(2+)-ATPase in diabetic rats.
abstract: The role of iron in the etiology of diabetes complications is not well established. Thus, this study was performed to test whether the iron-induced increase of oxidative/nitrative damage is involved in SERCA2a-related diabetic heart complication. Four randomly divided groups of rats were used: normal control group; iron overload group; diabetes group, and diabetic plus iron overload group. Iron supplementation stimulated cardiomyocyte hypertrophy and led to an increase in cardiac protein carbonyls, nitrotyrosine (3-NT) formation, and iNOS protein expression, thus resulting in abnormal myocardium calcium homeostasis of diabetic rats. The levels of SECA2a oxidation/nitration were significantly increased in the iron overload diabetic rats, along with a decrease in SECA2a expression and activity. In order to elucidate the possible role of iron in SERCA2a dysfunction, the effects of iron (Fe(3+) or hemin) on peroxynitrite (ONOO(-)) induced SERCA2a oxidation and nitration were further investigated in vitro. It was found that tyrosine nitration played more important role in SERCA2a inactivation than thiol oxidation. These results present a potential mechanism in which iron exacerbates the diabetes-induced oxidative/nitrative modification of SERCA2a, which may cause functional deficits in the myocyte associated with diabetic cardiac dysfunction. Our findings may help to further understand the role of iron in the pathogenesis of diabetic complications.
authors.affiliation: School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan 430074, PR China; Patent Examination Cooperation Hubei Center of the Patent Office, SIPO, Wuhan 430070, PR China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan 430074, PR China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan 430074, PR China; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, Wuhan 430074, PR China.
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Gao
authors.affiliation: School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan 430074, PR China; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, Wuhan 430074, PR China. Electronic address: lihailing86@hust.edu.cn.
authors.forename: Hailing
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D005033:Ethylmaleimide / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D019190:Iron Overload / Q000150:complications; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: C506948:Atp2a2 protein, rat; D007093:Imidazoles; D026361:Reactive Nitrogen Species; D007501:Iron; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D005033:Ethylmaleimide; C012160:N-acetylimidazole
keywords: Diabetic heart complications; Iron; SERCA2a; Tyrosine nitration