Melatonin protects against streptozotocin-induced diabetic cardiomyopathy by the phosphorylation of vascular endothelial growth factor-A (VEGF-A)

Yasemin Behram Kandemir; íœnal Guntekin; Veysel Tosun; Necmettin Korucuk; Mehmet Nuri Bozdemir

doi:10.14715/cmb/2018.64.14.8

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Vol. 64 No. 14: Issue 14

Issue Published : December 3, 2018

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Melatonin protects against streptozotocin-induced diabetic cardiomyopathy by the phosphorylation of vascular endothelial growth factor-A (VEGF-A)

https://doi.org/10.14715/cmb/2018.64.14.8

Yasemin Behram Kandemir

Department of Anatomy, Harran University Faculty of Medicine, Åžanlıurfa, Turkey

íœnal Guntekin

Department of Cardiology, Akdeniz University Faculty of Medicine, Antalya, Turkey

Veysel Tosun

Department of Cardiology, Åžanlıurfa Education and Research Hospital, Åžanlıurfa, Turkey

Necmettin Korucuk

Department of Cardiology, Private Medical Park Hospital, Antalya, Turkey

Mehmet Nuri Bozdemir

Department of Emergency Medicine, Antalya Education and Research Hospital, Antalya, Turkey

Corresponding Author(s) : Yasemin Behram Kandemir

ya_behram@hotmail.com

Cellular and Molecular Biology, Vol. 64 No. 14: Issue 14
Article Published : November 30, 2018

Abstract

The aim of the present study is to investigate if the melatonin has any protective effect on diabetic cardiomyopathy and antioxidant enzymes via phosphorylation of vascular endothelial growth factor-A (VEGF-A). A total of 40 male Wistar rats were enrolled in the study. Rats were divided into four groups: group 1 (control, n=10), group 2 (DM, n=10), group 3 (melatonin, n=10), and group 4 (melatonin+DM, n=10). Melatonin was injected intraperitoneally at a dose of 50 mg/kg/day for 56 days to group 3 and group 4. We investigated expression and phosphorylation of the VEGF-A in coronary vessels of all groups. Staining intensities, biochemical, immunohistochemistry analysis, and transthoracic echocardiography were performed. In comparison to the group 1, DM induced a decrease in p-VEGF-A in coronary vessels of group 2. The lower constitutive phosphorylation of VEGF-A in the group 2 was also increased in coronary vessels after melatonin treatment (p<0.05). Diabetic rats developed myocardial hypertrophy with preserved cardiac function (p<0.05). Cardio-protective effect of melatonin may reduce the damages of diabetes mellitus on the heart muscle fibers and coronary vessels via the phosphorylation of VEGF-A. Melatonin-dependent phosphorylation of VEGF-A in coronary angiogenesis may be associated with the physiological as well as with the pathological cardiac hypertrophy.

Keywords

Diabetic cardiomyopathy Diabetes mellitus Echocardiography Melatonin Vascular endothelial growth factor-A.

Behram Kandemir, Y., Guntekin, íœnal, Tosun, V., Korucuk, N., & Bozdemir, M. N. (2018). Melatonin protects against streptozotocin-induced diabetic cardiomyopathy by the phosphorylation of vascular endothelial growth factor-A (VEGF-A). Cellular and Molecular Biology, 64(14), 47–52. https://doi.org/10.14715/cmb/2018.64.14.8

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References

Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. Jun 2003; 9(6): 669-676.
Tammela T, Enholm B, Alitalo K, Paavonen K. The biology of vascular endothelial growth factors. Cardiovasc Res. Feb 15 2005; 65(3): 550-563.
Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. May 2006; 7(5): 359-371.
Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. Mar 30 2007; 100(6): 782-794.
Stehle JH, Saade A, Rawashdeh O et al. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. J Pineal Res. Aug 2011; 51(1): 17-43.
Reiter RJ. Mechanisms of cancer inhibition by melatonin. J Pineal Res. Oct 2004; 37(3): 213-214.
Reiter RJ, Tan DX, Galano A. Melatonin: exceeding expectations. Physiology (Bethesda). Sep 2014; 29(5): 325-333.
Chuffa LG, Fioruci-Fontanelli BA, Mendes LO et al. Melatonin attenuates the TLR4-mediated inflammatory response through MyD88- and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer. BMC Cancer. Feb 06 2015; 15: 34.
Oka T, Akazawa H, Naito AT, Komuro I. Angiogenesis and cardiac hypertrophy: maintenance of cardiac function and causative roles in heart failure. Circ Res. Jan 31 2014; 114(3): 565-571.
Forman JP, Curhan GC, Schernhammer ES. Urinary melatonin and risk of incident hypertension among young women. J Hypertens. Mar 2010; 28(3): 446-451.
Eilken HM, Adams RH. Dynamics of endothelial cell behavior in sprouting angiogenesis. Curr Opin Cell Biol. Oct 2010; 22(5): 617-625.
Hoyer DP, Korkmaz Y, Gronke S et al. Differential expression of protein kinase C isoforms in coronary arteries of diabetic mice lacking the G-protein Galpha11. Cardiovasc Diabetol. Dec 29 2010; 9: 93.
Reuter H, Seuthe K, Korkmaz Y et al. The G protein Galpha11 is essential for hypertrophic signalling in diabetic myocardium. Int J Cardiol. Aug 20 2013; 167(4): 1476-1485.
Korkmaz Y, Lang H, Beikler T et al. Irreversible inflammation is associated with decreased levels of the alpha1-, beta1-, and alpha2-subunits of sGC in human odontoblasts. J Dent Res. Apr 2011; 90(4): 517-522.
Wasowicz W, Neve J, Peretz A. Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem. Dec 1993; 39(12): 2522-2526.

References

Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. Jun 2003; 9(6): 669-676.

Tammela T, Enholm B, Alitalo K, Paavonen K. The biology of vascular endothelial growth factors. Cardiovasc Res. Feb 15 2005; 65(3): 550-563.

Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. May 2006; 7(5): 359-371.

Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. Mar 30 2007; 100(6): 782-794.

Stehle JH, Saade A, Rawashdeh O et al. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. J Pineal Res. Aug 2011; 51(1): 17-43.

Reiter RJ. Mechanisms of cancer inhibition by melatonin. J Pineal Res. Oct 2004; 37(3): 213-214.

Reiter RJ, Tan DX, Galano A. Melatonin: exceeding expectations. Physiology (Bethesda). Sep 2014; 29(5): 325-333.

Chuffa LG, Fioruci-Fontanelli BA, Mendes LO et al. Melatonin attenuates the TLR4-mediated inflammatory response through MyD88- and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer. BMC Cancer. Feb 06 2015; 15: 34.

Oka T, Akazawa H, Naito AT, Komuro I. Angiogenesis and cardiac hypertrophy: maintenance of cardiac function and causative roles in heart failure. Circ Res. Jan 31 2014; 114(3): 565-571.

Forman JP, Curhan GC, Schernhammer ES. Urinary melatonin and risk of incident hypertension among young women. J Hypertens. Mar 2010; 28(3): 446-451.

Eilken HM, Adams RH. Dynamics of endothelial cell behavior in sprouting angiogenesis. Curr Opin Cell Biol. Oct 2010; 22(5): 617-625.

Hoyer DP, Korkmaz Y, Gronke S et al. Differential expression of protein kinase C isoforms in coronary arteries of diabetic mice lacking the G-protein Galpha11. Cardiovasc Diabetol. Dec 29 2010; 9: 93.

Reuter H, Seuthe K, Korkmaz Y et al. The G protein Galpha11 is essential for hypertrophic signalling in diabetic myocardium. Int J Cardiol. Aug 20 2013; 167(4): 1476-1485.

Korkmaz Y, Lang H, Beikler T et al. Irreversible inflammation is associated with decreased levels of the alpha1-, beta1-, and alpha2-subunits of sGC in human odontoblasts. J Dent Res. Apr 2011; 90(4): 517-522.

Wasowicz W, Neve J, Peretz A. Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem. Dec 1993; 39(12): 2522-2526.

Author biographies is not available.