title: Involvement of caspases and their upstream regulators in myocardial apoptosis in a rat model of selenium deficiency-induced dilated cardiomyopathy.
abstract: Keshan disease is an endemic dilated cardiomyopathy (DCM) which is closely related with selenium-deficient diet in China. In the previous study, we reported that the low selenium status plays a pivotal role in the myocardial apoptosis in the DCM rats, however, the underlying mechanism remains unclear. The present study aimed to determine whether the intrinsic, extrinsic pathways and the upstream regulators were involved in the myocardial apoptosis of selenium deficiency-induced DCM rats. Therefore, the rat model of endemic DCM was induced by a selenium-deficient diet for 12 weeks. Accompanied with significant dilation and impaired systolic function of left ventricle, an enhanced myocardial apoptosis was detected by TUNEL assay. Western blot analysis showed remarkably increased protein levels of cleaved caspase-3, caspase-8, caspase-9, and cytosolic cytochrome c released from the mitochondria. In addition, the immunoreactivities of p53 and Bax were significantly up-regulated, while the anti-apoptotic Bcl-2 family members Bcl-2 and Bcl-X(L) were down-regulated. Furthermore, appropriate selenium supplement for another 4 weeks could partially reverse all the above changes. In conclusion, the intrinsic, extrinsic pathways and the upstream regulators such as p53, Bax, Bcl-2, and Bcl-X(L )were all involved in selenium deficiency-induced myocardial apoptosis.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an, Shaanxi 710004, China; Department of Endemic Disease, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Shan
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an, Shaanxi 710004, China; Department of Endemic Disease, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Diao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an, Shaanxi 710004, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Henan Provincial People's Hospital, 7 Weiwu Road, Zhengzhou, Henan, 450003, China.
authors.forename: Suqin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Trace Elements and Endemic Disease of Ministry of Health, Xi'an Jiaotong University School of Medicine, 76 Yantaxi Road, Xi'an, Shaanxi 710061, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Trace Elements and Endemic Disease of Ministry of Health, Xi'an Jiaotong University School of Medicine, 76 Yantaxi Road, Xi'an, Shaanxi 710061, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an, Shaanxi 710004, China; Department of Endemic Disease, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, 157 Xiwu Road, Xi'an, Shaanxi 710004, China. Electronic address: weijin2yuan@outlook.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000209:etiology; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000209:etiology*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D053181:Caspase 8 / Q000737:chemistry / Q000378:metabolism; D053453:Caspase 9 / Q000737:chemistry / Q000378:metabolism; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D053938:DNA Fragmentation; D003677:Deficiency Diseases / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019587:Dietary Supplements; D004452:Echocardiography; D004769:Enterovirus Infections / Q000000981:diagnostic imaging / Q000209:etiology; D006321:Heart / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use
chemical_list: D051017:Apoptosis Regulatory Proteins; D010446:Peptide Fragments; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D012643:Selenium
keywords: Caspase; Keshan disease; Myocardial apoptosis; Selenium deficiency