New insights into the molecular complexity of the ghrelin gene locus

Cytokine and Growth Factor Reviews

Volumn 20, Issue 4, 2009, Pages 297-304

  Seim, Inge ^a   Herington, Adrian C ^a   Chopin, Lisa K ^a  

^a QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

Author keywords

Alternative splicing; Crypteins; Ghrelin; ncRNA; Peptides

Indexed keywords

CRYPTEIN; GHRELIN; GHRELIN RECEPTOR; MESSENGER RNA; OBESTATIN; PREPROGHRELIN; PROOPIOMELANOCORTIN; PROTEIN PRECURSOR; UNCLASSIFIED DRUG;

5' UNTRANSLATED REGION; CARBOXY TERMINAL SEQUENCE; EXON; GENE EXPRESSION; GENE FUNCTION; GENE LOCUS; GENE STRUCTURE; GENETIC VARIABILITY; HUMAN; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN PROCESSING; PROTEIN RNA BINDING; REVIEW; RNA SPLICING; RNA TRANSCRIPTION; TRANSLATION REGULATION;

ALTERNATIVE SPLICING; ANIMALS; GHRELIN; HUMANS; MODELS, GENETIC; PROTEIN ISOFORMS; PROTEIN PRECURSORS; PROTEIN PROCESSING, POST-TRANSLATIONAL; RNA, ANTISENSE; TRANSCRIPTION, GENETIC;

EID: 69249229780     PISSN: 13596101     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2009.07.006     Document Type: Review

References (142)

1. Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., and Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402 (1999) 656-660
2. Howard A.D., Feighner S.D., Cully D.F., et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273 (1996) 974-977
3. Date Y., Kojima M., Hosoda H., et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 141 (2000) 4255-4261
4. Gnanapavan S., Kola B., Bustin S.A., et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87 (2002) 2988
5. Gronberg M., Tsolakis A.V., Magnusson L., Janson E.T., and Saras J. Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands. J Histochem Cytochem 56 (2008) 793-801
6. Volante M., Allia E., Gugliotta P., et al. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 87 (2002) 1300-1308
7. Ghelardoni S., Carnicelli V., Frascarelli S., Ronca-Testoni S., and Zucchi R. Ghrelin tissue distribution: comparison between gene and protein expression. J Endocrinol Invest 29 (2006) 115-121
8. Higgins S.C., Gueorguiev M., and Korbonits M. Ghrelin, the peripheral hunger hormone. Ann Med 39 (2007) 116-136
9. Leite-Moreira A.F., and Soares J.B. Physiological, pathological and potential therapeutic roles of ghrelin. Drug Discov Today 12 (2007) 276-288
10. Chen H.Y., Trumbauer M.E., Chen A.S., et al. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 145 (2004) 2607-2612
11. Cummings D.E., Frayo R.S., Marmonier C., Aubert R., and Chapelot D. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol Endocrinol Metab 287 (2004) E297-304
12. Cummings D.E., Purnell J.Q., Frayo R.S., Schmidova K., Wisse B.E., and Weigle D.S. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50 (2001) 1714-1719
13. Hewson A.K., and Dickson S.L. Systemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats. J Neuroendocrinol 12 (2000) 1047-1049
14. Lawrence C.B., Snape A.C., Baudoin F.M., and Luckman S.M. Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 143 (2002) 155-162
15. Tolle V., Bassant M.H., Zizzari P., et al. Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats. Endocrinology 143 (2002) 1353-1361
16. Toshinai K., Date Y., Murakami N., et al. Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 144 (2003) 1506-1512
17. Williams D.L., Grill H.J., Cummings D.E., and Kaplan J.M. Vagotomy dissociates short- and long-term controls of circulating ghrelin. Endocrinology 144 (2003) 5184-5187
18. Asakawa A., Inui A., Kaga T., et al. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 52 (2003) 947-952
19. Fujino K., Inui A., Asakawa A., Kihara N., Fujimura M., and Fujimiya M. Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats. J Physiol 550 (2003) 227-240
20. Inui A., Asakawa A., Bowers C.Y., et al. Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J 18 (2004) 439-456
21. Masuda Y., Tanaka T., Inomata N., et al. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 276 (2000) 905-908
22. Trudel L., Bouin M., Tomasetto C., et al. Two new peptides to improve post-operative gastric ileus in dog. Peptides 24 (2003) 531-534
23. Trudel L., Tomasetto C., Rio M.C., et al. Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat. Am J Physiol Gastrointest Liver Physiol 282 (2002) G948-952
24. Cassoni P., Allia E., Marrocco T., et al. Ghrelin and cortistatin in lung cancer: expression of peptides and related receptors in human primary tumors and in vitro effect on the H345 small cell carcinoma cell line. J Endocrinol Invest 29 (2006) 781-790
25. De Vriese C., and Delporte C. Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells. J Endocrinol 192 (2007) 199-205
26. Dixit V.D., Weeraratna A.T., Yang H., et al. Ghrelin and the growth hormone secretagogue receptor constitute a novel autocrine pathway in astrocytoma motility. J Biol Chem 281 (2006) 16681-16690
27. Duxbury M.S., Waseem T., Ito H., et al. Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness. Biochem Biophys Res Commun 309 (2003) 464-468
28. Jeffery P.L., Duncan R.P., Yeh A.H., et al. Expression of the ghrelin axis in the mouse: an exon 4-deleted mouse proghrelin variant encodes a novel C terminal peptide. Endocrinology 146 (2005) 432-440
29. Jeffery P.L., Herington A.C., and Chopin L.K. Expression and action of the growth hormone releasing peptide ghrelin and its receptor in prostate cancer cell lines. J Endocrinol 172 (2002) R7-11
30. Murata M., Okimura Y., Iida K., et al. Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J Biol Chem 277 (2002) 5667-5674
31. Waseem T., Javaid Ur R., Ahmad F., Azam M., and Qureshi M.A. Role of ghrelin axis in colorectal cancer: a novel association. Peptides 29 (2008) 1369-1376
32. Yeh A.H., Jeffery P.L., Duncan R.P., Herington A.C., and Chopin L.K. Ghrelin and a novel preproghrelin isoform are highly expressed in prostate cancer and ghrelin activates mitogen-activated protein kinase in prostate cancer. Clin Cancer Res 11 (2005) 8295-8303
33. Kanamoto N., Akamizu T., Hosoda H., et al. Substantial production of ghrelin by a human medullary thyroid carcinoma cell line. J Clin Endocrinol Metab 86 (2001) 4984-4990
34. Dixit V.D., Schaffer E.M., Pyle R.S., et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest 114 (2004) 57-66
35. Dixit V.D., and Taub D.D. Ghrelin and immunity: a young player in an old field. Exp Gerontol 40 (2005) 900-910
36. Koo G.C., Huang C., Camacho R., et al. Immune enhancing effect of a growth hormone secretagogue. J Immunol 166 (2001) 4195-4201
37. Li W.G., Gavrila D., Liu X., et al. Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation 109 (2004) 2221-2226
38. Zhao D., Zhan Y., Zeng H., Moyer M.P., Mantzoros C.S., and Pothoulakis C. Ghrelin stimulates interleukin-8 gene expression through protein kinase C-mediated NF-kappaB pathway in human colonic epithelial cells. J Cell Biochem 97 (2006) 1317-1327
39. Weikel J.C., Wichniak A., Ising M., et al. Ghrelin promotes slow-wave sleep in humans. Am J Physiol Endocrinol Metab 284 (2003) E407-415
40. Carlini V.P., Monzon M.E., Varas M.M., et al. Ghrelin increases anxiety-like behavior and memory retention in rats. Biochem Biophys Res Commun 299 (2002) 739-743
41. Nagaya N., Kojima M., Uematsu M., et al. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 280 (2001) R1483-1487
42. Nagaya N., Miyatake K., Uematsu M., et al. Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab 86 (2001) 5854-5859
43. Nagaya N., Uematsu M., Kojima M., et al. Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 104 (2001) 1430-1435
44. Tritos N.A., Kissinger K.V., Manning W.J., and Danias P.G. Association between ghrelin and cardiovascular indexes in healthy obese and lean men. Clin Endocrinol (Oxf) 60 (2004) 60-66
45. Caminos J.E., Tena-Sempere M., Gaytan F., et al. Expression of ghrelin in the cyclic and pregnant rat ovary. Endocrinology 144 (2003) 1594-1602
46. Gaytan F., Barreiro M.L., Caminos J.E., et al. Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors. J Clin Endocrinol Metab 89 (2004) 400-409
47. Gaytan F., Barreiro M.L., Chopin L.K., et al. Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in the cyclic human ovary. J Clin Endocrinol Metab 88 (2003) 879-887
48. Kawamura K., Sato N., Fukuda J., et al. Ghrelin inhibits the development of mouse preimplantation embryos in vitro. Endocrinology 144 (2003) 2623-2633
49. Tena-Sempere M., Barreiro M.L., Gonzalez L.C., et al. Novel expression and functional role of ghrelin in rat testis. Endocrinology 143 (2002) 717-725
50. Nakahara K., Hayashida T., Nakazato M., et al. Effect of chronic treatments with ghrelin on milk secretion in lactating rats. Biochem Biophys Res Commun 303 (2003) 751-755
51. Hosoda H., Kojima M., Matsuo H., and Kangawa K. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 279 (2000) 909-913
52. Hosoda H., Kojima M., Mizushima T., Shimizu S., and Kangawa K. Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing. J Biol Chem 278 (2003) 64-70
53. Pemberton C., Wimalasena P., Yandle T., Soule S., and Richards M. C-terminal pro-ghrelin peptides are present in the human circulation. Biochem Biophys Res Commun 310 (2003) 567-573
54. Zhang J.V., Ren P.G., Avsian-Kretchmer O., et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 310 (2005) 996-999
55. Hosoda H., Kojima M., Matsuo H., and Kangawa K. Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem 275 (2000) 21995-22000
56. Jeffery P.L., Herington A.C., and Chopin L.K. The potential autocrine/paracrine roles of ghrelin and its receptor in hormone-dependent cancer. Cytokine Growth Factor Rev 14 (2003) 113-122
57. Kineman R.D., Gahete M.D., and Luque R.M. Identification of a mouse ghrelin gene transcript that contains intron 2 and is regulated in the pituitary and hypothalamus in response to metabolic stress. J Mol Endocrinol 38 (2007) 511-521
58. Tanaka M., Hayashida Y., Nakao N., Nakai N., and Nakashima K. Testis-specific and developmentally induced expression of a ghrelin gene-derived transcript that encodes a novel polypeptide in the mouse. Biochim Biophys Acta 1522 (2001) 62-65
59. Autelitano D.J., Rajic A., Smith A.I., Berndt M.C., Ilag L.L., and Vadas M. The cryptome: a subset of the proteome, comprising cryptic peptides with distinct bioactivities. Drug Discov Today 11 (2006) 306-314
60. Pimenta D.C., and Lebrun I. Cryptides: buried secrets in proteins. Peptides 28 (2007) 2403-2410
61. Ueki N., Someya K., Matsuo Y., Wakamatsu K., and Mukai H. Cryptides: functional cryptic peptides hidden in protein structures. Biopolymers 88 (2007) 190-198
62. Nemeth E.F. The parathyroid polyhormone hypothesis revisited. Kidney Int Suppl (2006) S22-28
63. Raffin-Sanson M.L., de Keyzer Y., and Bertagna X. Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions. Eur J Endocrinol 149 (2003) 79-90
64. Wajnrajch M., Ten I., Gertner J., and Leibel R. Genomic organization of the GHRELIN gene. J Endocr Genet 1 (2000) 231-233
65. Kanamoto N., Akamizu T., Tagami T., et al. Genomic structure and characterization of the 5'-flanking region of the human ghrelin gene. Endocrinology 145 (2004) 4144-4153
66. Nakai N., Kaneko M., Nakao N., et al. Identification of promoter region of ghrelin gene in human medullary thyroid carcinoma cell line. Life Sci 75 (2004) 2193-2201
67. Seim I., Collet C., Herington A.C., and Chopin L.K. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. BMC Genomics 8 (2007) 298
68. Tanaka M., Hayashida Y., Iguchi T., Nakao N., Nakai N., and Nakashima K. Organization of the mouse ghrelin gene and promoter: occurrence of a short noncoding first exon. Endocrinology 142 (2001) 3697-3700
69. Seim I., Carter S.L., Herington A.C., and Chopin L.K. The proximal first exon architecture of the murine ghrelin gene is highly similar to its human orthologue. BMC Res Notes 2 (2009) 85
70. Petersenn S., Rasch A.C., Penshorn M., Beil F.U., and Schulte H.M. Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor. Endocrinology 142 (2001) 2649-2659
71. Gutierrez J.A., Solenberg P.J., Perkins D.R., et al. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci USA 105 (2008) 6320-6325
72. Yang J., Brown M.S., Liang G., Grishin N.V., and Goldstein J.L. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132 (2008) 387-396
73. Bang A.S., Soule S.G., Yandle T.G., Richards A.M., and Pemberton C.J. Characterisation of proghrelin peptides in mammalian tissue and plasma. J Endocrinol 192 (2007) 313-323
74. Bassil A.K., Haglund Y., Brown J., et al. Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract. Br J Pharmacol 150 (2007) 58-64
75. Chartrel N., Alvear-Perez R., Leprince J., et al. Comment on "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake". Science 315 (2007) 766 author reply 766
76. Lauwers E., Landuyt B., Arckens L., Schoofs L., and Luyten W. Obestatin does not activate orphan G protein-coupled receptor GPR39. Biochem Biophys Res Commun 351 (2006) 21-25
77. Nogueiras R., Pfluger P., Tovar S., et al. Effects of obestatin on energy balance and growth hormone secretion in rodents. Endocrinology 148 (2007) 21-26
78. Zizzari P., Longchamps R., Epelbaum J., and Bluet-Pajot M.T. Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents. Endocrinology 148 (2007) 1648-1653
79. Holst B., Egerod K.L., Schild E., et al. GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology 148 (2007) 13-20
80. Holst B., Holliday N.D., Bach A., Elling C.E., Cox H.M., and Schwartz T.W. Common structural basis for constitutive activity of the ghrelin receptor family. J Biol Chem 279 (2004) 53806-53817
81. Yasuda S., Miyazaki T., Munechika K., Yamashita M., Ikeda Y., and Kamizono A. Isolation of Zn2+ as an endogenous agonist of GPR39 from fetal bovine serum. J Recept Signal Transduct Res 27 (2007) 235-246
82. Pan W., Tu H., and Kastin A.J. Differential BBB interactions of three ingestive peptides: obestatin, ghrelin, and adiponectin. Peptides 27 (2006) 911-916
83. Anderwald-Stadler M., Krebs M., Promintzer M., et al. Plasma obestatin is lower at fasting and not suppressed by insulin in insulin-resistant humans. Am J Physiol Endocrinol Metab 293 (2007) E1393-1398
84. Beasley J.M., Ange B.A., Anderson C.A., Miller Iii E.R., Holbrook J.T., and Appel L.J. Characteristics associated with fasting appetite hormones (obestatin, ghrelin, and leptin). Obesity (Silver Spring) 17 (2009) 349-354
85. Butler M.G., and Bittel D.C. Plasma obestatin and ghrelin levels in subjects with Prader-Willi syndrome. Am J Med Genet A 143 (2007) 415-421
86. Fontenot E., DeVente J.E., and Seidel E.R. Obestatin and ghrelin in obese and in pregnant women. Peptides 28 (2007) 1937-1944
87. Gao X.Y., Kuang H.Y., Liu X.M., Ma Z.B., Nie H.J., and Guo H. Plasma obestatin levels in men with chronic atrophic gastritis. Peptides 29 (2008) 1749-1754
88. Gao X.Y., Kuang H.Y., Liu X.M., Wang X.Y., Pan Y.H., and Ma X.X. Decreased obestatin in plasma in metabolically obese, normal-weight men with normal glucose tolerance. Diabetes Res Clin Pract 79 (2008) e5-6
89. Ghanbari-Niaki A., Saghebjoo M., Rahbarizadeh F., Hedayati M., and Rajabi H. A single circuit-resistance exercise has no effect on plasma obestatin levels in female college students. Peptides 29 (2008) 487-490
90. Guo Z.F., Ren A.J., Zheng X., et al. Different responses of circulating ghrelin, obestatin levels to fasting, re-feeding and different food compositions, and their local expressions in rats. Peptides 29 (2008) 1247-1254
91. Guo Z.F., Zheng X., Qin Y.W., Hu J.Q., Chen S.P., and Zhang Z. Circulating preprandial ghrelin to obestatin ratio is increased in human obesity. J Clin Endocrinol Metab 92 (2007) 1875-1880
92. Harada T., Nakahara T., Yasuhara D., et al. Obestatin, acyl ghrelin, and des-acyl ghrelin responses to an oral glucose tolerance test in the restricting type of anorexia nervosa. Biol Psychiatry 63 (2008) 245-247
93. Huda M.S., Durham B.H., Wong S.P., et al. Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal. Int J Obes (Lond) 32 (2008) 129-135
94. Koca S.S., Ozgen M., Aydin S., Dag S., Evren B., and Isik A. Ghrelin and obestatin levels in rheumatoid arthritis. Inflammation 31 (2008) 329-335
95. Lippl F., Erdmann J., Lichter N., et al. Relation of plasma obestatin levels to bmi, gender, age and insulin. Horm Metab Res 40 (2008) 806-812
96. Manshouri M., Ghanbari-Niaki A., Kraemer R.R., and Shemshaki A. Time course alterations of plasma obestatin and growth hormone levels in response to short-term anaerobic exercise training in college women. Appl Physiol Nutr Metab 33 (2008) 1246-1249
97. Monteleone P., Serritella C., Martiadis V., Scognamiglio P., and Maj M. Plasma obestatin, ghrelin, and ghrelin/obestatin ratio are increased in underweight patients with anorexia nervosa but not in symptomatic patients with bulimia nervosa. J Clin Endocrinol Metab 93 (2008) 4418-4421
98. Nakahara T., Harada T., Yasuhara D., et al. Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa. Biol Psychiatry 64 (2008) 252-255
99. Ozbay Y., Aydin S., Dagli A.F., et al. Obestatin is present in saliva: alterations in obestatin and ghrelin levels of saliva and serum in ischemic heart disease. BMB Rep 41 (2008) 55-61
100. Park W.H., Oh Y.J., Kim G.Y., et al. Obestatin is not elevated or correlated with insulin in children with Prader-Willi syndrome. J Clin Endocrinol Metab 92 (2007) 229-234
101. Qi X., Li L., Yang G., et al. Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus. Clin Endocrinol (Oxf) 66 (2007) 593-597
102. Reinehr T., de Sousa G., and Roth C.L. Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight. Clin Endocrinol (Oxf) 68 (2008) 304-310
103. Roth C.L., Reinehr T., Schernthaner G.H., Kopp H.P., Kriwanek S., and Schernthaner G. Ghrelin and obestatin levels in severely obese women before and after weight loss after Roux-en-Y gastric bypass surgery. Obes Surg 19 (2009) 29-35
104. Sedlackova D., Dostalova I., Hainer V., et al. Simultaneous decrease of plasma obestatin and ghrelin levels after a high-carbohydrate breakfast in healthy women. Physiol Res 57 Suppl. 1 (2008) S29-37
105. Vicennati V., Genghini S., De Iasio R., Pasqui F., Pagotto U., and Pasquali R. Circulating obestatin levels and the ghrelin/obestatin ratio in obese women. Eur J Endocrinol 157 (2007) 295-301
106. Wang J., Chen C., and Wang R.Y. Influence of short- and long-term treadmill exercises on levels of ghrelin, obestatin and NPY in plasma and brain extraction of obese rats. Endocrine 33 (2008) 77-83
107. Zamrazilova H., Hainer V., Sedlackova D., et al. Plasma obestatin levels in normal weight, obese and anorectic women. Physiol Res 57 Suppl. 1 (2008) S49-55
108. Zou C.C., Liang L., Wang C.L., Fu J.F., and Zhao Z.Y. The change in ghrelin and obestatin levels in obese children after weight reduction. Acta Paediatr 98 (2009) 159-165
109. Granata R., Settanni F., Biancone L., et al. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3',5'-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. Endocrinology 148 (2007) 512-529
110. Camina J.P., Campos J.F., Caminos J.E., Dieguez C., and Casanueva F.F. Obestatin-mediated proliferation of human retinal pigment epithelial cells: regulatory mechanisms. J Cell Physiol 211 (2007) 1-9
111. Meszarosova M., Sirotkin A.V., Grossmann R., Darlak K., and Valenzuela F. The effect of obestatin on porcine ovarian granulosa cells. Anim Reprod Sci 108 (2008) 196-207
112. Pazos Y., Alvarez C.J., Camina J.P., and Casanueva F.F. Stimulation of extracellular signal-regulated kinases and proliferation in the human gastric cancer cells KATO-III by obestatin. Growth Factors 25 (2007) 373-381
113. Szentirmai E., and Krueger J.M. Obestatin alters sleep in rats. Neurosci Lett 404 (2006) 222-226
114. Carlini V.P., Schioth H.B., and Debarioglio S.R. Obestatin improves memory performance and causes anxiolytic effects in rats. Biochem Biophys Res Commun 352 (2007) 907-912
115. Samson W.K., White M.M., Price C., and Ferguson A.V. Obestatin acts in brain to inhibit thirst. Am J Physiol Regul Integr Comp Physiol 292 (2007) R637-643
116. Samson W.K., Yosten G.L., Chang J.K., Ferguson A.V., and White M.M. Obestatin inhibits vasopressin secretion: evidence for a physiological action in the control of fluid homeostasis. J Endocrinol 196 (2008) 559-564
117. Jeffery P.L., Murray R.E., Yeh A.H., et al. Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Endocr Relat Cancer 12 (2005) 839-850
118. Yang J., Zhao T.J., Goldstein J.L., and Brown M.S. Inhibition of ghrelin O-acyltransferase (GOAT) by octanoylated pentapeptides. Proc Natl Acad Sci USA 105 (2008) 10750-10755
119. Bednarek M.A., Feighner S.D., Pong S.S., et al. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem 43 (2000) 4370-4376
120. Tolle V., Zizzari P., Tomasetto C., Rio M.C., Epelbaum J., and Bluet-Pajot M.T. In vivo and in vitro effects of ghrelin/motilin-related peptide on growth hormone secretion in the rat. Neuroendocrinology 73 (2001) 54-61
121. Torsello A., Ghe C., Bresciani E., et al. Short ghrelin peptides neither displace ghrelin binding in vitro nor stimulate GH release in vivo. Endocrinology 143 (2002) 1968-1971
122. Dehlin E., Liu J., Yun S.H., et al. Regulation of ghrelin structure and membrane binding by phosphorylation. Peptides 29 (2008) 904-911
123. Clevenger C.V. Nuclear localization and function of polypeptide ligands and their receptors: a new paradigm for hormone specificity within the mammary gland?. Breast Cancer Res 5 (2003) 181-187
124. Fiaschi-Taesch N.M., and Stewart A.F. Minireview: parathyroid hormone-related protein as an intracrine factor-trafficking mechanisms and functional consequences. Endocrinology 144 (2003) 407-411
125. Miao D., Su H., He B., et al. Severe growth retardation and early lethality in mice lacking the nuclear localization sequence and C-terminus of PTH-related protein. Proc Natl Acad Sci USA 105 (2008) 20309-20314
126. Hughes T.A. Regulation of gene expression by alternative untranslated regions. Trends Genet 22 (2006) 119-122
127. Kozak M. Regulation of translation via mRNA structure in prokaryotes and eukaryotes. Gene 361 (2005) 13-37
128. Han B., Dong Z., Liu Y., Chen Q., Hashimoto K., and Zhang J.T. Regulation of constitutive expression of mouse PTEN by the 5'-untranslated region. Oncogene 22 (2003) 5325-5337
129. van der Velden A.W., van Nierop K., Voorma H.O., and Thomas A.A. Ribosomal scanning on the highly structured insulin-like growth factor II-leader 1. Int J Biochem Cell Biol 34 (2002) 286-297
130. Seim I., Carter S.L., Herington A.C., and Chopin L.K. Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate non-coding RNA gene. BMC Mol Biol 9 (2008) 95
131. Mercer T.R., Dinger M.E., Sunkin S.M., Mehler M.F., and Mattick J.S. Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci USA 105 (2008) 716-721
132. Ravasi T., Suzuki H., Pang K.C., et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. Genome Res 16 (2006) 11-19
133. Sasaki Y.T., Sano M., Ideue T., Kin T., Asai K., and Hirose T. Identification and characterization of human non-coding RNAs with tissue-specific expression. Biochem Biophys Res Commun 357 (2007) 991-996
134. Torarinsson E., Yao Z., Wiklund E.D., et al. Comparative genomics beyond sequence-based alignments: RNA structures in the ENCODE regions. Genome Res 18 (2008) 242-251
135. Eddy S.R. Non-coding RNA genes and the modern RNA world. Nat Rev Genet 2 (2001) 919-929
136. Griffiths-Jones S. Annotating noncoding RNA genes. Annu Rev Genomics Hum Genet 8 (2007) 279-298
137. Pheasant M., and Mattick J.S. Raising the estimate of functional human sequences. Genome Res 17 (2007) 1245-1253
138. Mattick J.S. Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. Bioessays 25 (2003) 930-939
139. He S., Su H., Liu C., et al. MicroRNA-encoding long non-coding RNAs. BMC Genomics 9 (2008) 236
140. Lee Y., Kim M., Han J., et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23 (2004) 4051-4060
141. Birney E., Stamatoyannopoulos J.A., Dutta A., et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447 (2007) 799-816
142. Singh J., Saxena A., Christodoulou J., and Ravine D. MECP2 genomic structure and function: insights from ENCODE. Nucleic Acids Res 36 (2008) 6035-6047