Effects of Neurotrophin Receptor-interacting MAGE Homolog on Apoptosis of Intestinal Epithelial Cells

FENG Qi, HU Yuan-liang, ZOU Gui-jun. et al

Abstract

To explore whether neurotrophin receptor-interacting MAGE homolog (NRAGE) is involved in the intestinal ischemia-reperfusion (I/R) and its effect on the apoptosis of intestinal epithelial cells and the expression of occludin protein. Methods The level of NRAGE protein after the rat small intestine I/R was detected by immunohistochemical (IHC) In vivo. The level of NRAGE protein and mRNA in IEC-6 cells after hypoxia and reoxygenation were tested by Western blot and RT-PCR respectively in vitro. The IEC-6 cells were divided into four groups, including NRAGE overexpression by lentivirus infection (Lv-NRAGE group), interference (sh-NRAGE group), lentivirus control (Lv-control group), and normal control group without lentivirus infection (NC group). The apoptosis of IEC-6 cells after infection was analyzed by flow cytometry. The level of the tight junction protein occludin was detected by Western blot. Results The expression of NRAGE were highly increased in intestinal mucosa epithelial cells after I/R (P<0.01). The proteins and mRNA levels of NRAGE were increased after 6 h of hypoxia in IEC-6 cellsin vitro. Compared with the Lv-control group, the early apoptosis rate was raised (P<0.01) and the level of occludin was reduced (P<0.01) in Lv-NRAGE group; while the early apoptosis rate was reduced (P<0.01) and the level of occludin was raised in sh-NRAGE group(P<0.001). Conclusion NRAGE may be involved in intestinal I/R and promote the apoptosis and decrease occludin expression of intestinal epithelial cells.

 

Keywords: NRAGE Ischemia-reperfusion injury, Intestinal epithelial cells, Cell apoptosis

 

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CERQUEIRA NF, HUSSNI CA, YOSHIDA WB. Pathophysiology of mesenteric ischemia/reperfusion: a review. Acta Cir Bras,2005,20(4) ;336-343.

HOTCHKISS RS, SC H MI EG RE, SWANSON PE, et al. Rapid onset of intestinal epithelial and lymphocyte apoptotic cell death in patients with trauma and shock. Crit Care Med, 2000,28(9):3207-3217.

IKEDA H, SUZUKI Y. SUZUKI M, et al. Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/ reperfusion injury to the rat intestinal epithelium. Out, 1998, 42(4) :530-537.

SALEHI AH, ROUX PP, KUBU CJ, et al. NR AGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis. Neuron,2000,27(2);279-288.

KENDALL SE, GOLDHAWK DE, KUBU C. et al. Expression analysis of a novel p75(NTR) signaling protein, which regulates cell cycle progression and apoptosis. Mech Develop, 2002,117(1 /2): 187-200.

BRAGASON ВТ, PALSDOTTIR A. Interaction of PrP with NRAGE, a protein involved in neuronal apoptosis. Mol Cell Neurosci,2005,29(2) :232-244.

DICERTOMG, CORBI N, BRUNO T, et al. NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death. J Cell Sci, 2007, 120 ( Pt 11):1852-1858.

BERTRAND MJ, KENCHAPPA RS, ANDRIEU D. et al. NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo. Cell Death Differ, 2008,15 (12): 1921-1929.

XUE В, WEN С, SHI Y. et al. Human NR AGE disrupts E- cadherin/beta-catenin regulated homotypic cell-cell adhesion. Biochem Bioph Res Co,2005,336(1) s247-251.

CHU CS, XUE B, TU C, et al. NR AGE suppresses metastasis of melanoma and pancreatic cancer in vitro and in vivo. Cancer Lett,2007,250(2);268-275.

NIKOPOULOS GN, MARTINS JF. ADAMS TL, el al. NRAGE; a potential rheostat during branching morphogenesis. Mech Develop,2009, 126(5/6) :337-349.

CHEN K, XIE W, LUO B, et al. Intestinal mucosal barrier is injured by BMP2/4 via activation of NF-кВ signals after ischemic reperfusion. Mediat Inflamm, 2014, 2014; 1-11 [2016-10-15]. http://dx. doi. org/10. 1155/2014/901530. doi: 10. 1155/2014/901530. 565 )

HARVEY JM, CLARK GM. OSBORNE C'K. et al. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol, 1999, 17 (5):1474-1481.

YANG Q. OU C, LIU M, et al. NRAGE promotes cell proliferation by stabilizing PCNA in a ubiquitin-proteasome pathway in esophageal carcinomas. Carcinogenesis, 2014 , 35(7):1643-1651.

DU Q, ZHANG Y, TIAN XX, et al. MAGE-D1 inhibits proliferation, migration and invasion of human breast cancer cells. Oncol Rep,2009,22(3) :659-665.

AL-SADI R. KHATIBK, GUO S, et al. Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier. Am J Physiol Gastr L.2011,300(6) ;G1054- G1064.

MATLUK N, ROCHIRA JA, KARACZYN A, et al. A role for NRAGE in NF-kappaB activation through the non- canonical BMP pathway. BMC Biol,2010,8; 7[2016-10-15]. http://bmcbiol. biomedcentral. com/articles/10. 1186/1741- 7007-8-7. doi: 10. 1186/1741-7007-8-7.

MUKOYAMA M.NAKAO К.SALTO Y,et al. Human brain natriuretic peptide,a novel cardiac hormone. Lancet,1990,335 (8692):801-802.

GUSTAFSSON F, STEENSGA ARD H F, BADSK H AER J , et al. Diagnostic and prognostic performance of N-terminal ProBNP in primary care patients with suspected heart failure. J Card Fail,2005,11(5): 15-20.

ZAPHIRIOU A, ROBBS S, MURRAY-THOMAS T. et al. The diagnostic accuracy of plasm BNP and NTproBNP in patients referred from primary care with suspected heart faiure: results of the UK natriuretic peptides study. Eur J Heart Fail.2005,7(4) ;537-541.

LAINCHBURY JG, TROUGHTON RW, STRANGMAN KM,W et al. N-terminal Pro-B-type natriuretic peptide-guided treatment for chronic heart failure; results from the BATTLESCARRED ( NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmission and death) trial. J Am Coll Cardiol,2009,55( 1); 53-60.

JANUZZI JL, Jr.CAMARGO CA,ANWARUDDIN S. et al. The N-terminal Pro-BNP investigation of dyspnea in Emergency Departmt( PRIDE) study. Am J Cardiol. 2005, 95 (8);948-954.

JANUZZI JL.VAN KIMMENADE R. LAINCHBURY J,et al. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients. Eur Heart J,2006,27(3);330-337.

CORTES R. PORTOLES M. ROSELLO-LLETI E, et al. Impact of glomerular filtration rate on urinary BNP and NT- proBNP levels in heart failure. Peptides, 2012, 33 ( 2 ): 354- 358.

TAKASE H.DOHI Y. Kidney function crucially affects B- type natriuretic peptide ( BNP), N-terminal pro BNP and their relationship. Eur J Clin Invest,2014,44(3) :303-308.

DEFILIPPI C, VAN KIMMENADE RR, PINTO YM. Amino-terminal pro-B-type natriuretic peptide testing in renal disease. Am J Cardiol,2008,101(3):82-88.


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