Skip to main content
SpringerLink
Log in

Selenium Deficiency Is Associated with Endoplasmic Reticulum Stress in a Rat Model of Cardiac Malfunction

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The relationship between selenium (Se) deficiency-induced cardiac malfunction and endoplasmic reticulum (ER) stress is poorly understood. In the present study, 18 weaning Sprague Dawley rats were randomly fed with three different Se diets, and myocardial glutathione peroxidase (GPx) activity was measured by an enzyme activity assay. Cardiac function was evaluated by hemodynamic parameters. ER stress markers immunoglobulin-binding protein (BiP)/glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were detected by western blotting. Our data showed that myocardial GPx activity and cardiac function were conspicuously impaired in Se-deficient rats. Expression of GRP78 and CHOP was significantly upregulated by treatment of Se deficiency. Improvements in myocardial GPx activity and cardiac function, as well as decreases in expression of GRP78 and CHOP, were observed after Se supplementation. Consequently, our data show that ER stress was involved in Se deficiency-induced cardiac dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Wang XZ, Lawson B, Brewer JW, Zinszner H, Sanjay A, Mi LJ, Boorstein R, Kreibich G, Hendershot LM, Ron D (1996) Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol Cell Biol 16(8):4273–4280

    PubMed  CAS  Google Scholar 

  2. Hetz C, Russelakis-Carneiro M, Maundrell K, Castilla J, Soto C (2003) Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. EMBO J 22(20):5435–5445

    Article  PubMed  CAS  Google Scholar 

  3. Hotamisligil GS (2005) Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes. Diabetes 54(Suppl 2):S73–S78

    Article  PubMed  CAS  Google Scholar 

  4. Xu J, Wang G, Wang Y, Liu Q, Xu W, Tan Y, Cai L (2009) Diabetes- and angiotensin II-induced cardiac endoplasmic reticulum stress and cell death: metallothionein protection. J Cell Mol Med 13(8A):1499–1512

    Article  PubMed  CAS  Google Scholar 

  5. Ceylan-Isik AF, Sreejayan N, Ren J (2011) Endoplasmic reticulum chaperon tauroursodeoxycholic acid alleviates obesity-induced myocardial contractile dysfunction. J Mol Cell Cardiol 50(1):107–116

    Article  PubMed  CAS  Google Scholar 

  6. Hamada H, Suzuki M, Yuasa S, Mimura N, Shinozuka N, Takada Y, Nishino T, Nakaya H, Koseki H, Aoe T (2004) Dilated cardiomyopathy caused by aberrant endoplasmic reticulum quality control in mutant KDEL receptor transgenic mice. Mol Cell Biol 24(18):8007–8017

    Article  PubMed  CAS  Google Scholar 

  7. Azfer A, Niu J, Rogers LM, Adamski FM, Kolattukudy PE (2006) Activation of endoplasmic reticulum stress response during the development of ischemic heart disease. Am J Physiol Heart Circ Physiol 291(3):H1411–H1420

    Article  PubMed  CAS  Google Scholar 

  8. Dally S, Monceau V, Corvazier E, Bredoux R, Raies A, Bobe R, del Monte F, Enouf J (2009) Compartmentalized expression of three novel sarco/endoplasmic reticulum Ca2+ ATPase 3 isoforms including the switch to ER stress, SERCA3f, in non-failing and failing human heart. Cell Calcium 45(2):144–154

    Article  PubMed  CAS  Google Scholar 

  9. Cheng WH, Ho YS, Valentine BA, Ross DA, Combs GF Jr, Lei XG (1998) Cellular glutathione peroxidase is the mediator of body selenium to protect against paraquat lethality in transgenic mice. J Nutr 128(7):1070–1076

    PubMed  CAS  Google Scholar 

  10. Xiang N, Zhao R, Zhong W (2009) Sodium selenite induces apoptosis by generation of superoxide via the mitochondrial-dependent pathway in human prostate cancer cells. Cancer Chemother Pharmacol 63(2):351–362

    Article  PubMed  CAS  Google Scholar 

  11. Ge K, Xue A, Bai J, Wang S (1983) Keshan disease—an endemic cardiomyopathy in China. Virchows Arch A Pathol Anat Histopathol 401(1):1–15

    Article  PubMed  CAS  Google Scholar 

  12. Yang J, Wang T, Wu C, Liu C (2010) Selenium level surveillance for the year 2007 of Keshan disease in endemic areas and analysis on surveillance results between 2003 and 2007. Biol Trace Elem Res 138(1–3):53–59

    Article  PubMed  CAS  Google Scholar 

  13. Wei HL, Pei JR, Jiang CX, Zhou LW, Lan T, Liu M, Wang T (2011) Analysis of glutathione peroxidase 1 gene polymorphism and Keshan disease in Heilongjiang Province, China. Genet Mol Res 10(4):2996–3001

    Article  PubMed  CAS  Google Scholar 

  14. Boldery R, Fielding G, Rafter T, Pascoe AL, Scalia GM (2007) Nutritional deficiency of selenium secondary to weight loss (bariatric) surgery associated with life-threatening cardiomyopathy. Heart Lung Circ 16(2):123–126

    Article  PubMed  Google Scholar 

  15. Saliba W, El Fakih R, Shaheen W (2010) Heart failure secondary to selenium deficiency, reversible after supplementation. Int J Cardiol 141(2):e26–e27

    Article  PubMed  CAS  Google Scholar 

  16. Al-Matary A, Hussain M, Ali J (2013) Selenium: a brief review and a case report of selenium responsive cardiomyopathy. BMC Pediatr 13:39

    Article  PubMed  Google Scholar 

  17. Cheng W, Fu YX, Porres JM, Ross DA, Lei XG (1999) Selenium-dependent cellular glutathione peroxidase protects mice against a pro-oxidant-induced oxidation of NADPH, NADH, lipids, and protein. FASEB J 13(11):1467–1475

    PubMed  CAS  Google Scholar 

  18. Liu ZW, Niu XL, Chen KL, Xing YJ, Wang X, Qiu C, Gao DF (2013) Selenium attenuates adriamycin-induced cardiac dysfunction via restoring expression of ATP-sensitive potassium channels in rats. Biol Trace Elem Res 153(1–3):220–228

    Article  PubMed  CAS  Google Scholar 

  19. Hirao A, Tahara Y, Kimura I, Shibata S (2009) A balanced diet is necessary for proper entrainment signals of the mouse liver clock. PLoS One 4(9):e6909

    Article  PubMed  Google Scholar 

  20. Roe ND, Ren J (2013) Oxidative activation of Ca(2+)/calmodulin-activated kinase II mediates ER stress-induced cardiac dysfunction and apoptosis. Am J Physiol Heart Circ Physiol 304(6):H828–H839

    Article  PubMed  CAS  Google Scholar 

  21. Metes-Kosik N, Luptak I, Dibello PM, Handy DE, Tang SS, Zhi H, Qin F, Jacobsen DW, Loscalzo J, Joseph J (2012) Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance. Mol Nutr Food Res 56(12):1812–1824

    Article  PubMed  CAS  Google Scholar 

  22. Tripp MJ, Whanger PD, Schmitz JA (1993) Calcium uptake and ATPase activity of sarcoplasmic reticulum vesicles isolated from control and selenium deficient lambs. J Trace Elem Electrolyte Health Dis 7(2):75–82

    CAS  Google Scholar 

  23. Wang YZ, Jia XA, Zhao JY, Xu GL (1993) Effects of selenium deficiency on Ca transport function of sarcoplasmic reticulum and lipid peroxidation in rat myocardium. Biol Trace Elem Res 36(2):159–166

    Article  PubMed  CAS  Google Scholar 

  24. Treiman M, Caspersen C, Christensen SB (1998) A tool coming of age: thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPases. Trends Pharmacol Sci 19(4):131–135

    Article  PubMed  CAS  Google Scholar 

  25. Li Y, Zhu W, Tao J, Xin P, Liu M, Li J, Wei M (2012) Fasudil protects the heart against ischemia-reperfusion injury by attenuating endoplasmic reticulum stress and modulating SERCA activity: the differential role for PI3K/Akt and JAK2/STAT3 signaling pathways. PLoS One 7(10):e48115

    Article  PubMed  CAS  Google Scholar 

  26. Uguz AC, Naziroglu M, Espino J, Bejarano I, Gonzalez D, Rodriguez AB, Pariente JA (2009) Selenium modulates oxidative stress-induced cell apoptosis in human myeloid HL-60 cells through regulation of calcium release and caspase-3 and -9 activities. J Membr Biol 232(1–3):15–23

    PubMed  CAS  Google Scholar 

  27. Yao HD, Wu Q, Zhang ZW, Zhang JL, Li S, Huang JQ, Ren FZ, Xu SW, Wang XL, Lei XG (2013) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of SE-deficient chicks. J Nutr 143(5):613–619

    Article  PubMed  CAS  Google Scholar 

  28. Talukder MA, Zweier JL, Periasamy M (2009) Targeting calcium transport in ischaemic heart disease. Cardiovasc Res 84(3):345–352

    Article  PubMed  CAS  Google Scholar 

  29. Lipskaia L, Chemaly ER, Hadri L, Lompre AM, Hajjar RJ (2010) Sarcoplasmic reticulum Ca(2+) ATPase as a therapeutic target for heart failure. Expert Opin Biol Ther 10(1):29–41

    Article  PubMed  CAS  Google Scholar 

  30. Kawase Y, Hajjar RJ (2008) The cardiac sarcoplasmic/endoplasmic reticulum calcium ATPase: a potent target for cardiovascular diseases. Nat Clin Pract Cardiovasc Med 5(9):554–565

    Article  PubMed  CAS  Google Scholar 

  31. Xin W, Lu X, Li X, Niu K, Cai J (2011) Attenuation of endoplasmic reticulum stress-related myocardial apoptosis by SERCA2a gene delivery in ischemic heart disease. Mol Med 17(3–4):201–210

    PubMed  CAS  Google Scholar 

  32. Knight SA, Sunde RA (1987) The effect of progressive selenium deficiency on anti-glutathione peroxidase antibody reactive protein in rat liver. J Nutr 117(4):732–738

    PubMed  CAS  Google Scholar 

  33. Lei XG, Cheng WH, McClung JP (2007) Metabolic regulation and function of glutathione peroxidase-1. Annu Rev Nutr 27:41–61

    Article  PubMed  CAS  Google Scholar 

  34. Sunde RA, Raines AM, Barnes KM, Evenson JK (2009) Selenium status highly regulates selenoprotein mRNA levels for only a subset of the selenoproteins in the selenoproteome. Biosci Rep 29(5):329–338

    Article  PubMed  CAS  Google Scholar 

  35. Moserova I, Kralova J (2012) Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways. PLoS One 7(3):e32972

    Article  PubMed  CAS  Google Scholar 

  36. Ermak G, Davies KJ (2002) Calcium and oxidative stress: from cell signaling to cell death. Mol Immunol 38(10):713–721

    Article  PubMed  CAS  Google Scholar 

  37. Bhandary B, Marahatta A, Kim HR, Chae HJ (2012) An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases. Int J Mol Sci 14(1):434–456

    Article  PubMed  Google Scholar 

  38. Bruce JI, Elliott AC (2007) Oxidant-impaired intracellular Ca2+ signaling in pancreatic acinar cells: role of the plasma membrane Ca2+-ATPase. Am J Physiol Cell Physiol 293(3):C938–C950

    Article  PubMed  CAS  Google Scholar 

  39. Malhotra JD, Kaufman RJ (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9(12):2277–2293

    Article  PubMed  CAS  Google Scholar 

  40. Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH (2003) Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nat Cell Biol 5(12):1051–1061

    Article  PubMed  CAS  Google Scholar 

  41. Szegezdi E, Duffy A, O'Mahoney ME, Logue SE, Mylotte LA, O'Brien T, Samali A (2006) ER stress contributes to ischemia-induced cardiomyocyte apoptosis. Biochem Biophys Res Commun 349(4):1406–1411

    Article  PubMed  CAS  Google Scholar 

  42. Thuerauf DJ, Marcinko M, Gude N, Rubio M, Sussman MA, Glembotski CC (2006) Activation of the unfolded protein response in infarcted mouse heart and hypoxic cultured cardiac myocytes. Circ Res 99(3):275–282

    Article  PubMed  CAS  Google Scholar 

  43. Severino A, Campioni M, Straino S, Salloum FN, Schmidt N, Herbrand U, Frede S, Toietta G, Di Rocco G, Bussani R, Silvestri F, Piro M, Liuzzo G, Biasucci LM, Mellone P, Feroce F, Capogrossi M, Baldi F, Fandrey J, Ehrmann M, Crea F, Abbate A, Baldi A (2007) Identification of protein disulfide isomerase as a cardiomyocyte survival factor in ischemic cardiomyopathy. J Am Coll Cardiol 50(11):1029–1037

    Article  PubMed  CAS  Google Scholar 

  44. Toko H, Takahashi H, Kayama Y, Okada S, Minamino T, Terasaki F, Kitaura Y, Komuro I (2010) ATF6 is important under both pathological and physiological states in the heart. J Mol Cell Cardiol 49(1):113–120

    Article  PubMed  CAS  Google Scholar 

  45. Sawada T, Minamino T, Fu HY, Asai M, Okuda K, Isomura T, Yamazaki S, Asano Y, Okada K, Tsukamoto O, Sanada S, Asanuma H, Asakura M, Takashima S, Kitakaze M, Komuro I (2010) X-box binding protein 1 regulates brain natriuretic peptide through a novel AP1/CRE-like element in cardiomyocytes. J Mol Cell Cardiol 48(6):1280–1289

    Article  PubMed  CAS  Google Scholar 

  46. Okada K, Minamino T, Tsukamoto Y, Liao Y, Tsukamoto O, Takashima S, Hirata A, Fujita M, Nagamachi Y, Nakatani T, Yutani C, Ozawa K, Ogawa S, Tomoike H, Hori M, Kitakaze M (2004) Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosis. Circulation 110(6):705–712

    Article  PubMed  Google Scholar 

  47. Isodono K, Takahashi T, Imoto H, Nakanishi N, Ogata T, Asada S, Adachi A, Ueyama T, Oh H, Matsubara H (2010) PARM-1 is an endoplasmic reticulum molecule involved in endoplasmic reticulum stress-induced apoptosis in rat cardiac myocytes. PLoS One 5(3):e9746

    Article  PubMed  Google Scholar 

  48. Fu HY, Okada K, Liao Y, Tsukamoto O, Isomura T, Asai M, Sawada T, Okuda K, Asano Y, Sanada S, Asanuma H, Asakura M, Takashima S, Komuro I, Kitakaze M, Minamino T (2010) Ablation of C/EBP homologous protein attenuates endoplasmic reticulum-mediated apoptosis and cardiac dysfunction induced by pressure overload. Circulation 122(4):361–369

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant no. 30972557).

Conflict of interest

The authors declare no competing interests.

Author information

Authors and Affiliations

  1. Department of Cardiology, Second Affiliated Hospital, Xi’an Jiaotong University, 157 Road Xiwu, Xi’an, Shaanxi, 710004, People’s Republic of China

    Su-Qin Wang, Xiao-Lin Niu, Zhong-Wei Liu & Deng-Feng Gao

  2. Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China

    Yan-He Zhu

Authors
  1. Su-Qin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Lin Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhong-Wei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan-He Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Deng-Feng Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiao-Lin Niu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, SQ., Niu, XL., Liu, ZW. et al. Selenium Deficiency Is Associated with Endoplasmic Reticulum Stress in a Rat Model of Cardiac Malfunction. Biol Trace Elem Res 156, 196–201 (2013). https://doi.org/10.1007/s12011-013-9834-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-013-9834-1

Keywords

Search

Navigation