Skip to main content
SpringerLink
Log in

Selenium restores defective beta-adrenergic receptor response of thoracic aorta in diabetic rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Increased oxidative stress is one of the basic contributors to the development of the cardiovascular complications in diabetes. Both endothelial and vascular smooth muscle cell dysfunctions are the main sign involved in the pathogenesis of diabetic cardiovascular dysfunction. Matrix metalloproteinases (MMPs) are expressed in the vasculature, and participate in tissue remodeling under pathological conditions such as increased oxidative stress, whereas little is known about effect of hyperglycemia on regulation of MMPs in vascular system. Therefore, we aimed to evaluate the effect of an antioxidant, sodium selenate treatment (0.3 mg/kg for 4 weeks) on function of streptozotocin-diabetic rat aorta. Sodium selenate treatment improved significantly impaired isoproterenol-induced relaxation responses and contraction responses of the aortic strips, and exhibited marked protection against diabetes-induced degenerative changes in the smooth muscle cell morphology. Biochemical data showed that sodium selenate treatment induced a significant regulation of MMP-2 activity and protein loss as well as normalization of increased levels of tissue nitrite and protein thiol oxidation. In addition, this treatment restored diabetes-induced increased levels of endothelin-1, PKC, and cAMP production in the aortic tissue. Taken together, our data demonstrate that these beneficial effects of sodium selenate treatment in diabetics are related to be not only inhibition of increased oxidative stress but also prevention of both receptor- and smooth muscle-mediated dysfunction of vasculature, in part, via regulation of MMP-2. Such an observation provides evidence for potential therapeutic usage of selenium compounds for the amelioration of vascular disorders in diabetes.

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
Fig. 4

Similar content being viewed by others

References

  1. Björkhem I, Henriksson-Freyschuss A, Breuer O, Diczfalusy U, Berglund L, Henriksson P (1991) The antioxidant butylated hydroxytoluene protects against atherosclerosis. Arterioscler Thromb 11:15–22

    PubMed  Google Scholar 

  2. Lu X, Liu S, Man RY (1994) Enhancement of endothelium dependent relaxation in the rat aortic ring by selenium supplement. Cardiovasc Res 28:345–348

    Article  CAS  PubMed  Google Scholar 

  3. Furchgott RF, Vanhoutt PM (1989) Endothelium-derived relaxing and contracting factors. FASEB J 3:2007–2018

    CAS  PubMed  Google Scholar 

  4. Hardman JG (1984) Cyclic nucleotides and regulation of vascular smooth muscle. J Cardiovasc Pharmacol 6:639–645

    Article  CAS  Google Scholar 

  5. Son SM (2007) Role of vascular reactive oxygen species in development of vascular abnormalities in diabetes. Diabetes Res Clin Prac 77:65–70

    Article  Google Scholar 

  6. Dollery CM, McEwan JR, Henney AM (1995) Matrix metalloproteinases and cardiovascular disease. Circ Res 77:863–868

    CAS  PubMed  Google Scholar 

  7. Limb GA, Matter K, Murphy G, Cambrey AD, Bishop PN, Morris GE, Khaw PT (2005) Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis. Am J Pathol 166:1555–1563

    CAS  PubMed  Google Scholar 

  8. Pustovrh MC, Jawerbaum A, Capobianco E, White V, Martínez N, López-Costa JJ, González E (2005) Oxidative stress promotes the increase of matrix metalloproteinases-2 and -9 activities in the feto-placental unit of diabetic rats. Free Radic Res 39:1285–1293

    Article  CAS  PubMed  Google Scholar 

  9. Moshal KS, Metreveli N, Tyagi SC (2008) Mitochondrial matrix metalloproteinase activation and dysfunction in hyperhomocysteinemia. Curr Vasc Pharmacol 6:84–92

    Article  CAS  PubMed  Google Scholar 

  10. McNeill JH, Delgatty HL, Battell ML (1991) Insulin like effects of sodium selenate in streptozocin-induced diabetic rats. Diabetes 40:1675–1678

    Article  CAS  PubMed  Google Scholar 

  11. Ayaz M, Can B, Ozdemir S, Turan B (2002) Protective effect of selenium treatment on diabetes-induced myocardial structural alterations. Biol Trace Elem Res 89:215–226

    Article  CAS  PubMed  Google Scholar 

  12. Ersöz G, Yakaryılmaz A, Turan B (2003) Effect of antioxidant treatment on platelet aggregation of streptozotocin-induced diabetic rats. Thromb Res 111:363–367

    Article  PubMed  Google Scholar 

  13. Kiersztan A, Baranska A, Hapka M, Lebiedzinska M, Winiarska K, Dudziak M, Bryla J (2009) Differential action of methylselenocysteine in control and alloxan-diabetic rabbits. Chem Biol Interact 177:161–171

    Article  CAS  PubMed  Google Scholar 

  14. Chew P, Yuen DY, Koh P, Stefanovic N, Febbraio MA, Kola I, Cooper ME, de Haan JB (2009) Site-specific antiatherogenic effect of the antioxidant ebselen in the diabetic apolipoprotein E-deficient mouse. Arterioscler Thromb Vasc Biol 29:823–830

    Article  CAS  PubMed  Google Scholar 

  15. Yaras N, Sariahmetoglu M, Bilginoglu A, Aydemir-Koksoy A, Onay-Besikci A, Turan B, Schulz R (2008) Protective action of doxycycline against diabetic cardiomyopathy in rats. Br J Pharmacol 155:1174–1184

    Article  CAS  PubMed  Google Scholar 

  16. Gurdal H, Can A, Ugur M (2005) The role of nitric oxide synthase in reduced vasocontractile responsiveness induced by prolonged alpha 1-adrenergic receptor stimulation in rat thoracic aorta. Br J Pharmacol 145:203–210

    Article  PubMed  Google Scholar 

  17. Gao CQ, Sawicki G, Suarez-Pinzon WL, Cson T, Wozniak M, Ferdinandy P, Schulz R (2003) Matrix metalloproteinase-2 mediates cytokine-induced myocardial contractile dysfunction. Cardiovasc Res 57:426–433

    Article  CAS  PubMed  Google Scholar 

  18. Tunctan B, Uludag O, Altug S, Abacioglu N (1998) Effects of nitric oxide synthase inhibition in lipopolysaccharide-induced sepsis in mice. Pharmacol Res 38:405–411

    Article  CAS  PubMed  Google Scholar 

  19. Bilginoglu A, Seymen A, Tuncay E, Zeydanli E, Aydemir-Koksoy A, Turan B (2009) Antioxidants but not doxycycline treatments restore depressed beta-adrenergic responses of the heart in diabetic rats. Cardiovasc Toxicol 9:21–29

    Article  CAS  PubMed  Google Scholar 

  20. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    Article  CAS  PubMed  Google Scholar 

  21. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H (2000) High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49:1939–1945

    Article  CAS  PubMed  Google Scholar 

  22. Ulusu NN, Turan B (2005) Beneficial effects of selenium on some enzymes of diabetic rat heart. Biol Trace Elem Res 103:207–216

    Article  CAS  PubMed  Google Scholar 

  23. Kamata K, Miyata N, Abiru T, Kasuya Y (1992) Functional changes in vascular smooth muscle and endothelium of arteries during diabetes mellitus. Life Sci 50:1379–1387

    Article  CAS  PubMed  Google Scholar 

  24. Lee TS, Saltsman KA, Ohashi H, King GL (1989) Activation of protein kinase C by elevation of glucose concentration: proposal for a mechanism in the development of diabetic vascular complications. Proc Natl Acad Sci USA 86:5141–5145

    Article  CAS  PubMed  Google Scholar 

  25. Chisolm GM, Steinberg D (2000) The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 28:1815–1826

    Article  CAS  PubMed  Google Scholar 

  26. Bendeck MP, Conte M, Zhang M, Nili N, Strauss BH, Farwell SM (2002) Doxycycline modulates smooth muscle cell growth, migration and matrix remodeling after arterial injury. Am J Pathol 160(3):1089–1095

    CAS  PubMed  Google Scholar 

  27. Clements RT, Sodha NR, Feng J, Boodhwani M, Liu Y, Mieno S, Khabbaz KR, Bianchi C, Sellke FW (2009) Impaired coronary microvascular dilation correlates with enhanced vascular smooth muscle MLC phosphorylation in diabetes. Microcirculation 16:193–206

    Article  CAS  PubMed  Google Scholar 

  28. Pierce GN, Dhalla NS (1985) Mechanisms of the defect of cardiac myofibrillar function during diabetes. Am J Physiol Endocrinol Metabo 248:E170–E175

    CAS  Google Scholar 

  29. Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS (1996) Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Investig 98:2572–2579

    Article  CAS  PubMed  Google Scholar 

  30. Uemura S, Matsushita H, Li W, Glassford AJ, Asagami T, Lee KH, Harrison DG, Tsao PS (2001) Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress. Circ Res 88:1291–1298

    Article  CAS  PubMed  Google Scholar 

  31. Portik-Dobos V, Anstadt MP, Hutchinson J, Bannan M, Ergul A (2002) Evidence for a matrix metalloproteinase induction/activation system in arterial vasculature and decreased synthesis and activity in diabetes. Diabetes 51:3063–3068

    Article  CAS  PubMed  Google Scholar 

  32. Elgebaly MM, Kelly A, Harris AK, Elewa H, Portik-Dobos V, Ketsawatsomkron P, Marrero M, Ergul A (2008) Impaired insulin-mediated vasorelaxation in a nonobese model of type 2 diabetes: role of endothelin-1. Can J Physiol Pharmacol 86(6):358–364

    Article  CAS  PubMed  Google Scholar 

  33. Fernandez-Patron C, Stewart KG, Zhang Y, Koivunen E, Radomsk MW, Davidge ST (2000) Vascular matrix metalloproteinase-2 dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction. Circ Res 87:670–676

    CAS  PubMed  Google Scholar 

  34. Matsumoto T, Kobayashi T, Kamata K (2008) Relationships among ET-1, PPAR, oxidative stress and endothelial dysfunction in diabetic animals. J Smooth Muscle Res 44(2):41–55

    Article  PubMed  Google Scholar 

  35. Skalska AB, Pietrzycka A, Stepniewski M (2009) Correlation of endothelin 1 plasma levels with plasma antioxidant capacity in elderly patients treated for hypertension. Clin Biochem 42:358–364

    Article  CAS  PubMed  Google Scholar 

  36. Raffetto JD, Khalil RA (2008) Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 75:346–359

    Article  CAS  PubMed  Google Scholar 

  37. Brenneisen P, Steinbrenner H, Sies H (2005) Selenium, oxidative stress and health aspects. Mol Aspects Med 26:256–267

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Drs. R. Schulz, C. Cansiz, and A. Koksoy for their scientific and technical contributions to this article. This work has been supported by grants from TUBITAK-SBAG-107S304, -SBAG-107S427 and COST BM0602 to Dr. B.Turan.

Author information

Authors and Affiliations

  1. Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey

    Esma N. Zeydanli, Ayca Bilginoglu, Evrim Tanriverdi & Belma Turan

  2. Department of Pharmacology, Faculty of Medicine, Ankara University, Ankara, Turkey

    Hakan Gurdal

Authors
  1. Esma N. Zeydanli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayca Bilginoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evrim Tanriverdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hakan Gurdal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Belma Turan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Belma Turan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zeydanli, E.N., Bilginoglu, A., Tanriverdi, E. et al. Selenium restores defective beta-adrenergic receptor response of thoracic aorta in diabetic rats. Mol Cell Biochem 338, 191–201 (2010). https://doi.org/10.1007/s11010-009-0353-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-009-0353-5

Keywords

Search

Navigation