Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating the mTOR signaling pathway

International Journal of Molecular Medicine

Volumn 32, Issue 4, 2013, Pages 851-859

  Zhang, Hongwei ^a   Cui, Zhongyi ^b   Luo, Guangwei ^a   Zhang, Jiaheng ^a   Ma, Tao ^a   Hu, Na ^a   Cui, Tianpen ^a  

^a HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b GUANGDONG MEDICAL UNIVERSITY   (China)

Author keywords

D Lys3 GHRP6; Ghrelin; Intestinal ischemia reperfusion; Mammalian target of rapamycin p70 ribosomal S6 kinase signaling pathway; Pro inflammatory cytokines

Indexed keywords

CYTOKINE; GHRELIN; INTERLEUKIN 6; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN P70; S6 KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; INTESTINE ISCHEMIA; INTRACELLULAR SIGNALING; LUNG PARENCHYMA; MALE; MOUSE; NEUTROPHIL CHEMOTAXIS; NONHUMAN; ORGAN INJURY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REPERFUSION INJURY; SMALL INTESTINE; STOMACH PROTECTION; SUPERIOR MESENTERIC ARTERY OBSTRUCTION; SURVIVAL;

ANIMALS; GHRELIN; INFLAMMATION; INTERLEUKIN-1BETA; INTERLEUKIN-6; INTESTINES; LUNG; MALE; MICE; MICE, INBRED C57BL; NEUTROPHIL INFILTRATION; PEROXIDASE; PHOSPHORYLATION; REPERFUSION INJURY; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84883318120     PISSN: 11073756     EISSN: 1791244X     Source Type: Journal    
DOI: 10.3892/ijmm.2013.1452     Document Type: Article

References (50)

1. Oldenburg WA, Lau LL, Rodenberg TJ, Edmonds HJ and Burger CD: Acute mesentericischemia: a clinical review. Arch Intern Med 164: 1054-1062, 2004.
2. Berlanga J, Prats P, Remirez D, Gonzalez R, Lopez-Saura P, et al: Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage. Am J Pathol 161: 373-379, 2002.
3. Tendler DA: Acute intestinal ischemia and infarction. Semin Gastrointest Dis 14: 66-76, 2003.
4. Zhang M and Carroll MC: Natural antibody mediated innate autoimmune response. Mol Immunol 44: 103-110, 2007.
5. Leaphart CL and Tepas JJ III: The gut is a motor of organ system dysfunction. Surgery 141: 563-569, 2007.
6. Rotstein OD: Pathogenesis of multiple organ dysfunction syndrome: gut origin, protection, and decontamination. Surg Infect (Larchmt) 1: 217-225, 2000.
7. Tsang CK, Qi H, Liu LF and Zheng XF: Targeting mammalian target of rapamycin (mTOR) for health and diseases. Drug Discov Today 12: 112-124, 2007.
8. Weichhart T: Mammalian target of rapamycin: a signaling kinase for every aspect of cellular life. Methods Mol Biol 821: 1-14, 2012.
9. Yang Q and Guan KL: Expanding mTOR signaling. Cell Res 17: 666-681, 2012.
10. Zoncu R, Efeyan A and Sabatini DM: mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12: 21-35, 2011.
11. Hay N and Sonenberg N: Upstream and downstream of mTOR. Genes Dev 18: 1926-1945, 2004.
12. Koh PO: Melatonin prevents ischemic brain injury through activation of the mTOR/p70S6 kinase signaling pathway. Neurosci Lett 444: 74-78, 2008.
13. Koh PO: Ginkgo biloba extract (EGb 761) prevents cerebral ischemia-induced p70S6 kinase and S6 phosphorylation. Am J Chin Med 38: 727-734, 2010.
14. Shi GD, OuYang Y.P, Shi JG, Liu Y, Yuan W and Jia LS: PTEN deletion prevents ischemic brain injury by activating the mTOR signaling pathway. Biochem Biophys Res Commun 404: 941-945, 2011.
15. Vigneron F, Dos Santos P, Lemoine S, Bonnet M, Tariosse L, Couffinhal T, Duplaà C and Jaspard-Vinassa B: GSK-3? at the crossroads in the signalling of heart preconditioning: implication of mTOR and Wnt pathways. Cardiovasc Res 90: 49-56, 2011.
16. 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: 656-660, 1999.
17. Arvat E, Di Vito L, Broglio F, Papotti M, Muccioli G, et al: Preliminary evidence that Ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans. J Endocrinol Invest 23: 493-495, 2000.
18. Wu JT and Kral JG: Ghrelin: integrative neuroendocrine peptide in health and disease. Ann Surg 239: 464-474, 2004.
19. Cowley MA and Grove KL: Ghrelin - satisfying a hunger for the mechanism. Endocrinology 145: 2604-2606, 2004.
20. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, Palaniappan R, Lillard JW Jr and Taub DD: Ghrelin inhibits leptin- and activation-induced pro-inflammatory cytokine expression by human monocytes and T cells. J Clin Invest 114: 57-66, 2004.
21. Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S, Stoll LL, McCormick ML, Sigmund CD, Tang C and Weintraub NL: Ghrelin inhibits pro-inflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation 109: 2221-2226, 2004.
22. Konturek PC, Brzozowski T, Walter B, Burnat G, Hess T, Hahn EG and Konturek SJ: Ghrelin-induced gastroprotection against ischemia-reperfusion injury involves an activation of sensory afferent nerves and hyperemia mediated by nitric oxide. Eur J Pharmacol 536: 171-181, 2006.
23. Brzozowski T, Konturek PC, Sliwowski Z, Pajdo R, Drozdowicz D, Kwiecien S, Burnat G, Konturek S and Pawlik WW: Prostaglandin/cyclooxygenase pathway in ghrelin-induced gastroprotection against ischemia-reperfusion injury. J Pharmacol Exp Ther 319: 477-487, 2006.
24. Brzozowski T, Konturek PC, Sliwowski Z, Drozdowicz D, Kwiecien S, Pawlik M, Pajdo R, Konturek SJ, Pawlik WW and Hahn EG: Neural aspects of ghrelin-induced gastroprotection against mucosal injury induced by noxious agents. J Physiol Pharmacol 57 (Suppl 6): S63-S76, 2006.
25. Pawlik MW, Obuchowicz R, Biernat J, Szczepanski W, Pajdo R, Kwiecie? S, Brzozowski T, Konturek SJ and Pawlik WW: Effects of peripherally and centrally applied ghrelin in the pathogenesis of ischemia-reperfusion induced injury of the small intestine. J Physiol Pharmacol 62: 429-439, 2011.
26. Wu R, Dong W, Ji Y, Zhou M, Marini CP, Ravikumar TS and Wang P: Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemia-reperfusion. PLoS One 3: e2026, 2008.
27. Weichhart T, Costantino G, Poglitsch M, Rosner M, Zeyda M, et al: The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 29: 565-577, 2008.
28. Chiu CJ, McArdle AH, Brown R, Scott HJ and Gurd FN: Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 101: 478-483, 1970.
29. Bachofen M and Weibel ER: Structural alterations of lung parenchyma in the adult respiratory distress syndrome. Clin Chest Med 3: 35-56, 1982.
30. Collard CD and Gelman S: Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology 94: 1133-1138, 2001.
31. Hattori N, Saito T, Yagyu T, Jiang BH, Kitagawa K, et al: GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab 86: 4284-4291, 2001.
32. Papotti M, Ghe C, Cassoni P, Catapano F, Deghenghi R, et al: Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab 85: 3803-3807, 2000.
33. Shuto Y, Shibasaki T, Wada K, Parhar I, Kamegai J, et al: Generation of polyclonal antiserum against the growth hormone secretagogue receptor (GHS-R): evidence that the GHS-R exists in the hypothalamus, pituitary and stomach of rats. Life Sci 68: 991-996, 2001.
34. Wu R, Dong W, Cui X, Zhou M, Simms HH, et al: Ghrelin down-regulates pro-inflammatory cytokines in sepsis through activation of the vagus nerve. Ann Surg 245: 480-486, 2007.
35. Kojima M and Kangawa K: Ghrelin: structure and function. Physiol Rev 85: 495-522, 2005.
36. Wang G, Lee HM, Englander E and Greeley GH Jr: Ghrelin-not just another stomach hormone. Regul Pept 105: 75-81, 2002.
37. Kim DH and Sabatini DM: Raptor and mTOR: subunits of a nutrient-sensitive complex. Curr Top Microbiol Immunol 279: 259-270, 2004.
38. Montagne J, Stewart MJ, Stocker H, Hafen E, Kozma SC and Thomas G: Drosophila S6 kinase: a regulator of cell size. Science 285: 2126-2119, 1999.
39. Shima H, Pende M, Chen Y, Fumagalli S, Thomas G and Kozma SC: Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J 17: 6649-6659, 1998.
40. Lawrence JC Jr and Brunn GJ: Insulin signaling and the control of PHAS-I phosphorylation. Prog Mol Subcell Biol 26: 1-31, 2001.
41. Janelidze S, Hu BR, Siesjö P and Siesjö BK: Alterations of Akt1 (PKBalpha) and p70(S6K) in transient focal ischemia. Neurobiol Dis 8: 147-154, 2001.
42. Mengesdorf T, Proud CG, Mies G and Paschen W: Mechanisms underlying suppression of protein synthesis induced by transient focal cerebral ischemia in mouse brain. Exp Neurol 177: 538-546, 2002.
43. Koh PO, Cho JH, Won CK, Lee HJ, Sung JH and Kim MO: Estradiol attenuates the focal cerebral ischemic injury through mTOR/p70S6 kinase signaling pathway. Neurosci Lett 436: 62-66, 2008.
44. Weichhart T and Säemann MD: The multiple facets of mTOR in immunity. Trends Immunol 30: 218-226, 2009.
45. Baker AK, Wang R, Mackman N and Luyendyk JP: Rapamycin enhances LPS induction of tissue factor and tumor necrosis factor-alpha expression in macrophages by reducing IL-10 expression. Mol Immunol 46: 2249-2255, 2009.
46. Aoyagi T, Kusakari Y, Xiao CY, Inouye BT, Takahashi M, Scherrer-Crosbie M, Rosenzweig A, Hara K and Matsui T: Cardiac mTOR protects the heart against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 303: H75-H85, 2012.
47. Wu R, Dong W, Zhou M, Zhang F, Marini CP, Ravikumar TS and Wang P: Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats. Am J Respir Crit Care Med 176: 805-813, 2007.
48. Sato N, Moore FA, Smith MA, Zou L, Moore-Olufemi S, et al: Immune-enhancing enteral nutrients differentially modulate the early pro-inflammatory transcription factors mediating gut ischemia/reperfusion. J Trauma 58: 455-461, 2005.
49. Mendes Sdos S, Candi A, Vansteenbrugge M, Pignon MR, Bult H, Boudjeltia KZ, Munaut C and Raes M: Microarray analyses of the effects of NF-kappaB or PI3K pathway inhibitors on the LPS-induced gene expression profile in RAW264.7 cells: synergistic effects of rapamycin on LPS-induced MMP9-overexpression. Cell Signal 21: 1109-1122, 2009.
50. Martins L, Fernández-Mallo D, Novelle MG, Vázquez MJ, Tena-Sempere M, Nogueiras R, López M and Diéguez C: Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin. PLoS One 7: e46923, 2012.