BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Obestatin is present in saliva: alterations in obestatin and ghrelin levels of saliva and serum in ischemic heart disease

  • Ozbay, Yilmaz (Department of Cardiology, Firat University, School of Medicine (Firat Medical Center)) ;
  • Aydin, Suleyman (Department of Biochemistry and Clinical Biochemistry, School of Medicine (Firat Medical Center)) ;
  • Dagli, A. Ferda (Department of Pathology, School of Medicine (Firat Medical Center)) ;
  • Akbulut, Mehmet (Department of Cardiology, Firat University, School of Medicine (Firat Medical Center)) ;
  • Dagli, Necati (Department of Cardiology, Firat University, School of Medicine (Firat Medical Center)) ;
  • Kilic, Nermin (Department of Biochemistry and Clinical Biochemistry, School of Medicine (Firat Medical Center)) ;
  • Rahman, Ali (Department of Cardiovascular Surgery, School of Medicine (Firat Medical Center)) ;
  • Sahin, Ibrahim (Department of Biochemistry and Clinical Biochemistry, School of Medicine (Firat Medical Center)) ;
  • Polat, Veli (Department of Cardiology, Firat University, School of Medicine (Firat Medical Center)) ;
  • Ozercan, H. Ibrahim (Department of Pathology, School of Medicine (Firat Medical Center)) ;
  • Arslan, Nadi (Department of Cardiology, Firat University, School of Medicine (Firat Medical Center)) ;
  • Sensoy, Dogan (Kirli Health)
  • Published : 2008.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Ghrelin and obestatin are a single gene products and are a multiple functional peptides that regulates energy homeostasis, and food intake. In the present work, we studied the secretion of ghrelin and its co-secreted peptide obestatin in 44 patients with ischemic heart disease with that of 27 healthy matched controls. Here we first conducted using an immunohistochemistry assay to screen whether human salivary glands have any obestatin immunoreactivity. Then, serum and saliva obestatin and acylated ghrelin levels were determined by using Radioimmunoassay. Our immunohistochemical analysis demonstrated that obestatin was localized in the striated and excretory duct of human salivary gland. We also report for the first time that obestatin, like ghrelin, is present in human salivary gland and saliva. No evidence of the role of obestatin or ghrelin saliva levels in the context of ischemic heart disease was found. Salivary ghrelin and obestatin levels are correlated in controls with the blood levels. Determination of salivary values could represent a non-invasive alternative to serum ones that can be useful in clinical practice.

Keywords

References

  1. Barton, M. (2000) Endothelial dysfunction and atherosclerosis: endothelin receptor antagonists as novel therapeutics. Curr. Hypertens. Rep. 2, 84-91. https://doi.org/10.1007/s11906-000-0064-5
  2. Farmer, J. A. and Torre-Amione, G. (2002) Atherosclerosis and inflammation. Curr. Atheroscler. Rep. 4, 92-98. https://doi.org/10.1007/s11883-002-0031-5
  3. Baxter, G. F. (2004) Natriuretic peptides and myocardial ischaemia. Basic Res. Cardiol. 99, 90-93. https://doi.org/10.1007/s00395-004-0458-7
  4. Brooks, W. W., Conrad, C. H. and Morgan, J. P. (1995) Reperfusion induced arrhythmias following ischaemia in intact rat heart: role of intracellular calcium. Cardiovasc. Res. 29, 536-542. https://doi.org/10.1016/S0008-6363(96)88531-2
  5. Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H. and Kangawa, K. (1999) Ghrelin is a growth-hormone- releasing acylated peptide from stomach. Nature 402, 656-659. https://doi.org/10.1038/45230
  6. Nagaya, N., Kojima, M., Uematsu, M., Yamagishi, M., Hosoda, H., Oya, H., Hayashi, Y. and Kangawa, K. (2001) Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, 1483-1487. https://doi.org/10.1152/ajpregu.2001.280.5.R1483
  7. Li, L., Zhang, L. K., Pang, Y. Z., Pan, C. S., Qi, Y. F., Chen, L., Wang, X., Tang, C. S. and Zhang, J. (2006) Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats. Acta Pharmacol. Sin. 27, 527-535. https://doi.org/10.1111/j.1745-7254.2006.00319.x
  8. Lin, Y., Matsumura, K., Fukuhara, M., Kagiyama, S., Fujii, K. and Iida, M. (2004) Ghrelin acts at the nucleus of the solitary tract to decrease arterial pressure in rats. Hypertension 43, 977-982. https://doi.org/10.1161/01.HYP.0000122803.91559.55
  9. Aydin, S. (2007a) Discovery of ghrelin hormone: researches and clinical applications. Turk. J. Biochem. 32, 76-89.
  10. Aydin, S., Ozkan, Y., Caylak, E. and Aydin, S. (2006) Ghrelin and its biochemical functions. J. Med. Sci. 26, 272-283.
  11. Kojima, M. and Kangawa, K. (2005) Ghrelin: structure and function. Physiol. Rev. 85, 495-522. https://doi.org/10.1152/physrev.00012.2004
  12. Gnanapavan, S., Kola, B., Bustin, S. A., Morris, D. G., McGee, P., Fairclough, P., Bhattacharya, S., Carpenter, R., Grossman, A. B. and Korbonits, M. (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J. Clin. Endocrinol. Metab. 87, 2988. https://doi.org/10.1210/jc.87.6.2988
  13. Papotti M., Ghe C., Cassoni P., Catapano F., Deghenghi R., Ghigo E. and Muccioli G. (2000) Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab. 85, 3803-3807 https://doi.org/10.1210/jc.85.10.3803
  14. Baldanzi, G., Filigheddu, N., Cutrupi, S., Catapano, F., Bonissoni, S., Fubini, A., Malan, D., Baj, G., Granata, R., Broglio, F., Papotti, M., Surico, N., Bussolino, F., Isgaard, J., Deghenghi, R., Sinigaglia, F., Prat, M., Muccioli, G., Ghigo, E. and Graziani, A. (2002) Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J. Cell Biol. 159, 1029-1037. https://doi.org/10.1083/jcb.200207165
  15. Bedendi, I., Alloatti, G., Marcantoni, A., Malan, D., Catapano, F., Ghe, C., Deghenghi, R., Ghigo, E. and Muccioli, G. (2003) Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14- ghrelin. Eur. J. Pharmacol. 476, 87-95 https://doi.org/10.1016/S0014-2999(03)02083-1
  16. Kleinz, M. J., Maguire, J. J., Skepper, J. N. and Davenport, A. P. (2006) Functional and immunocytochemical evidence for a role of ghrelin and des-octanoyl ghrelin in the regulation of vascular tone in man. Cardiovasc. Res. 69, 227-235. https://doi.org/10.1016/j.cardiores.2005.09.001
  17. Tsubota, Y., Owada-Makabe, K., Yukawa K. and Maeda, M. (2005) Hypotensive effect of des-acyl ghrelin at nucleus tractus solitarii of rat. Neuroreport 16, 163-166. https://doi.org/10.1097/00001756-200502080-00019
  18. Zhang, J. V., Ren, P. G., Avsian-Kretchmer, O., Luo, C. W., Rauch, R., Klein, C. and Hsueh, A. J. (2005) Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 310, 996-999. https://doi.org/10.1126/science.1117255
  19. Pammer, J., Weninger,W., Mildner, M., Burian, M., Wojta, J. and Tschachler, E. (1998) Vascular endothelial growth factor is constitutively expressed in normal human salivary glands and is secreted in the saliva of healthy individuals. J. Pathol. 186, 186-191. https://doi.org/10.1002/(SICI)1096-9896(1998100)186:2<186::AID-PATH148>3.0.CO;2-J
  20. Aydin, S., Ozercan, I. H., Dagli, F., Aydin, S., Dogru, O., Celebi, S., Akin, O. and Guzel, S. P. (2005b) Ghrelin immunohistochemistry of gastric adenocarcinoma and mucoepidermoid carcinoma of salivary gland. Biotech. Histochem. 80, 163-168. https://doi.org/10.1080/10520290500387847
  21. Lantini, M. S. and Cossu, M. (1998) Immunocytochemical investigation of the subcellular distribution of some secretory products in human salivary glands. Eur. J. Morphol. 36 Suppl, 230-234.
  22. Groschl, M., Topf, H. G., Bohlender, J., Zenk, J., Klussmann, S., Dotsch, J., Rascher, W. and Rauh, M. (2005) Identification of ghrelin in human saliva: production by the salivary glands and potential role in proliferation of oral keratinocytes. Clin. Chem. 51, 997-1006. https://doi.org/10.1373/clinchem.2004.040667
  23. Aydin, S., Halifeoglu, I., Ozercan, I. H., Erman, F., Kilic, N., Aydin, S., Ilhan, N., Ilhan, N., Ozkan, Y., Akpolat, N., Sert, L. and Caylak, E. (2005a) A comparison of leptin and ghrelin levels in plasma and saliva of young healthy subjects. Peptides 26, 647-652. https://doi.org/10.1016/j.peptides.2004.11.008
  24. Groschl, M., Topf, H. G., Rauh M., Kurzai M., Rascher, W. and Köhler H. (2006) Postprandial response of salivary ghrelin and leptin to carbohydrate uptake. Gut 55, 433-434. https://doi.org/10.1136/gut.2005.082255
  25. Frascarelli, S., Ghelardoni, S., Ronca-Testoni, S. and Zucchi, R. (2003) Effect of ghrelin and synthetic growth hormone secretagogues in normal and ischemic rat heart. Basic Res. Cardiol. 98, 401-405. https://doi.org/10.1007/s00395-003-0434-7
  26. Iglesias, M. J., Salgado, A., Pineiro, R., Rodino, B. K., Otero, M. F., Grigorian, L., Gallego, R., Dieguez, C., Gualillo, O., Gonzalez-Juanatey, J. R. and Lago, F. (2007) Lack of effect of the ghrelin gene-derived peptide obestatin on cardiomyocyte viability and metabolism. J. Endocrinol. Invest. 30, 470-476. https://doi.org/10.1007/BF03346330
  27. Otto, B., Cuntz, U., Fruehauf, E., Wawarta, R., Folwaczny, C., Riepl, R. L., Heiman, M. L., Lehnert, P., Fichter, M. and Tschop, M. (2001) Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur. J. Endocrinol. 145, 669-673. https://doi.org/10.1530/eje.0.1450669
  28. Rigamonti, A. E., Pincelli, A. I., Corra, B., Viarengo, R., Bonomo, S. M., Galimberti, D., Scacchi, M., Scarpini, E., Cavagnini, F. and Muller, E. E. (2002) Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients. J. Endocrinol. 175, 1-5. https://doi.org/10.1677/joe.0.1750001
  29. Hosada, H., Doi, K., Nagaya, N., Okumura, H., Nakagawa, E., Enomoto, M., Ono, F. and Kangawa, K. (2004) Optimum collection and storage conditions for ghrelin measurements: octanoyl modification of ghrelin is rapidly hydrolyzed to deacyl ghrelin in blood samples. Clin. Chem. 50, 1077-1080. https://doi.org/10.1373/clinchem.2003.025841
  30. Hsu, S. M., Raine, L. and Fanger, H. (1981) Use of avidinbiotinperoxidase complex (ABC) in immunoperoxidase technique. J. Histochem. Cytochem. 29, 577-580. https://doi.org/10.1177/29.4.6166661
  31. Aydin, S. (2007b) A comparison of ghrelin, glucose, alpha- amylase and protein levels in saliva from diabetics. J. Biochem. Mol. Biol. 40, 29-35. https://doi.org/10.5483/BMBRep.2007.40.1.029

Cited by

  1. Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes vol.173, pp.14, 2016, https://doi.org/10.1111/bph.13502
  2. New insights into the molecular complexity of the ghrelin gene locus vol.20, pp.4, 2009, https://doi.org/10.1016/j.cytogfr.2009.07.006
  3. Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms vol.11, pp.1, 2012, https://doi.org/10.1186/1475-2840-11-129
  4. Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway 2017, https://doi.org/10.1111/jcmm.13277
  5. Cardiovascular actions of the ghrelin gene-derived peptides and growth hormone-releasing hormone vol.236, pp.5, 2011, https://doi.org/10.1258/ebm.2011.010365
  6. Circulating ghrelin/obestatin ratio in subjects with Helicobacter pylori infection vol.25, pp.5, 2009, https://doi.org/10.1016/j.nut.2008.11.002
  7. Diet-induced obesity suppresses ghrelin in rat gastrointestinal tract and serum vol.355, pp.1-2, 2011, https://doi.org/10.1007/s11010-011-0867-5
  8. Antioxidant Defense System after Single and Chronic Administration of Obestatin and Its Fragment (1-4) to Normal and Overweight Male Rats vol.159, pp.1, 2015, https://doi.org/10.1007/s10517-015-2884-y
  9. The ghrelin-obestatin system in health and disease vol.86, pp.12, 2014, https://doi.org/10.17116/terarkh20148612116-120
  10. The Acute Salivary Ghrelin Response to a Psychosocial Stress Is Enhanced in Symptomatic Patients with Bulimia Nervosa: A Pilot Study vol.66, pp.4, 2012, https://doi.org/10.1159/000341877
  11. Effect of obestatin on insulin, glucagon and somatostatin secretion in the perfused rat pancreas vol.152, pp.1-3, 2009, https://doi.org/10.1016/j.regpep.2008.08.003
  12. Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro vol.23, 2017, https://doi.org/10.12659/MSM.901361
  13. Obestatin: An Interesting but Controversial Gut Hormone vol.59, pp.2-4, 2011, https://doi.org/10.1159/000334106
  14. Nesfatin-1 and ghrelin levels in serum and saliva of epileptic patients: hormonal changes can have a major effect on seizure disorders vol.328, pp.1-2, 2009, https://doi.org/10.1007/s11010-009-0073-x
  15. Cardioprotective Effect of Ghrelin in Cardiopulmonary Bypass Involves a Reduction in Inflammatory Response vol.8, pp.1, 2013, https://doi.org/10.1371/journal.pone.0055021
  16. Human saliva cortisone and cortisol simultaneous analysis using reverse phase HPLC technique vol.405, pp.1-2, 2009, https://doi.org/10.1016/j.cca.2009.04.006
  17. The expanding roles of the ghrelin-gene derived peptide obestatin in health and disease vol.340, pp.1, 2011, https://doi.org/10.1016/j.mce.2011.03.018
  18. Effects of ghrelin on homocysteine-induced dysfunction and inflammatory response in rat cardiac microvascular endothelial cells vol.36, pp.6, 2012, https://doi.org/10.1042/CBI20110235
  19. Comparison of Serum and Salivary Ghrelin in Healthy Adults, Morbidly Obese, and Patients with Metastatic Carcinoma vol.21, pp.8, 2011, https://doi.org/10.1007/s11695-010-0161-8
  20. Presence of obestatin in breast milk: Relationship among obestatin, ghrelin, and leptin in lactating women vol.24, pp.7-8, 2008, https://doi.org/10.1016/j.nut.2008.03.020
  21. Decreased saliva/serum irisin concentrations in the acute myocardial infarction promising for being a new candidate biomarker for diagnosis of this pathology vol.56, 2014, https://doi.org/10.1016/j.peptides.2014.04.002
  22. Saliva diagnostics – Current views and directions vol.242, pp.5, 2017, https://doi.org/10.1177/1535370216681550
  23. Breast Milk Hormones and Their Protective Effect on Obesity vol.2009, pp.1, 2009, https://doi.org/10.1186/1687-9856-2009-327505
  24. Decreased gastric body mucosa obestatin expression in overweight and obese patients vol.31, pp.2, 2010, https://doi.org/10.1016/j.peptides.2009.11.001
  25. Metabolic hormones in saliva: origins and functions vol.19, pp.3, 2013, https://doi.org/10.1111/odi.12015
  26. Expression of obestatin and ghrelin in papillary thyroid carcinoma vol.323, pp.1-2, 2009, https://doi.org/10.1007/s11010-008-9969-0
  27. Obestatin attenuated doxorubicin-induced cardiomyopathy via enhancing long noncoding Mhrt RNA expression vol.81, 2016, https://doi.org/10.1016/j.biopha.2016.04.017
  28. Alteration in chromogranin A, obestatin and total ghrelin levels of saliva and serum in epilepsy cases vol.31, pp.5, 2010, https://doi.org/10.1016/j.peptides.2010.02.009
  29. The roles of salivary secretion, brain–gut peptides, and oral hygiene in obesity vol.7, pp.5, 2013, https://doi.org/10.1016/j.orcp.2013.05.001
  30. Ghrelin and obestatin expression in oral squamous cell carcinoma: an immunohistochemical and biochemical study vol.339, pp.1-2, 2010, https://doi.org/10.1007/s11010-009-0381-1
  31. Plasma ghrelin level and plasma ghrelin/obestatin ratio are related to intestinal metaplasia in elderly patients with functional dyspepsia vol.12, pp.4, 2017, https://doi.org/10.1371/journal.pone.0175231
  32. Obestatin affords cardioprotection to the ischemic-reperfused isolated rat heart and inhibits apoptosis in cultures of similarly stressed cardiomyocytes vol.299, pp.2, 2010, https://doi.org/10.1152/ajpheart.00800.2009
  33. Azioni biologiche e metaboliche di obestatin, un peptide della famiglia del gene ghrelin vol.14, pp.6, 2013, https://doi.org/10.1007/BF03346110