대한의생명과학회지 (Biomedical Science Letters)

  • 제16권4호
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  • Pages.359-363
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  • 2010
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  • 1738-3226(pISSN)
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  • 2288-7415(eISSN)
대한의생명과학회 (The Korean Society for Biomedical Laboratory Sciences)
권호 표지

Intestine Ischemia/reperfusion Induces ER Stress and Apoptosis in Miniature Pigs

  • ;
  • ;
  • 박수현 (전남대학교 수의과대학 생리학교실)
  • Lim, Jae-Cheong (Bio-therapy Human Resources Center, Animal Medical Center, Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University) ;
  • Han, Ho-Jae (Bio-therapy Human Resources Center, Animal Medical Center, Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University) ;
  • Park, Soo-Hyun (Bio-therapy Human Resources Center, Animal Medical Center, Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University)
  • 투고 : 2010.11.25
  • 심사 : 2010.12.10
  • 발행 : 2010.12.31
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초록

The miniature pig is a very suitable donor species in xenotransplantation of human organs. Intestine ischemia/reperfusion (I/R) is associated with high morbidity and mortality. Endoplasmic reticulum (ER) stress and apoptosis has been associated with the onset of diverse diseases. Thus, we examined the effect of intestine I/R on the expression of ER stress and apotptosis related molecules. In the present study, I/R induced phosphorylation of protein kinase-like endoplasmic reticulum kinase (PERK), IRE, and ATF-4. I/R also increased the expression of the proapoptotic transcription factor CAAT/enhancer-binding protein homologous protein (CHOP). In addition, I/R decreased the expression of Bcl-2, but increased the expression of Bax, cleaved PARP, and cleaved caspase-3. Moreover, I/R increased splicing form of XBP-1 mRNA and the expression of caspase-6 and caspase-3 mRNA. In conclusion, intestine I/R induced ER stress and apoptosis in miniature pig.

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참고문헌

  1. Alnemri ES. Mammalian cell death proteases: a family of highly conserved aspartate specific cysteine proteases. J Cell Biochem. 1997.64: 33-42. https://doi.org/10.1002/(SICI)1097-4644(199701)64:1<33::AID-JCB6>3.0.CO;2-0
  2. Boyle EM Jr, Pohlman TH, Cornejo CJ, Verrier ED. Endothelial cell injury in cardiovascular surgery: ischemia-reperfusion. Ann Thorac Surg. 1996. 62: 1868-1875. https://doi.org/10.1016/S0003-4975(96)00950-2
  3. Chen X, Shen J, Prywes R. The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi. J Biol Chem. 2002. 277: 13045-13052. https://doi.org/10.1074/jbc.M110636200
  4. Choi JH, Choi AY, Yoon H, Choe W, Yoon KS, Ha J, Yeo EJ, Kang I. Baicalein protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis through inhibition of reactive oxygen spccies production and CHOP induction. Exp Mol Med. 2010 (in press).
  5. Crissinger RL, Dahlgren DN. Mucosal injury induced by ischemia and reperfusion in the piglet intestine: influence of age and feeding. Gastroenterology 1989. 97: 920-926.
  6. Debatin KM. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immun. 2004. 53: 153-159. https://doi.org/10.1007/s00262-003-0474-8
  7. Doroudgar S, Thuerauf DJ, Marcinko MC, Belmont PJ, Glembotski CC. Ischemia activates the ATF6 branch of the endoplasmic reticulum stress response. J Biol Chem. 2009. 284: 29735-29745. https://doi.org/10.1074/jbc.M109.018036
  8. Duan SR, Wang JX, Wang J, Xu R, Zhao JK, Wang DS. Ischemia induces endoplasmic reticulum stress and cell apoptosis in human brain. Neurosci Lett. 2010. 475: 132-135. https://doi.org/10.1016/j.neulet.2010.03.058
  9. Grootjans J, Hodin CM, de Haan JJ, Derikx JP, Rouschop KM, Verheyen FK, van Dam RM, Dejong CH, Buurman WA, Lenaerts K. Level of activation of the unfolded protein response correlates with Paneth cell apoptosis in human small intestine exposed to ischemia-reperfusion. Gastroenterology 2010 (in press).
  10. Hengartner MO. The biochemistry of apoptosis. Nature 2000. 407: 770-777. https://doi.org/10.1038/35037710
  11. Kaufman RJ, Scheuner D, Schroder M, Shen X, Lee K, Liu CY, Arnold SM. The unfolded protein response in nutrient sensing and differentiation. Nat Rev Mol Cell Biol. 2002.3: 411-421. https://doi.org/10.1038/nrm829
  12. Kinross J, Warren O, Basson S, Holmes E, Silk D, Darzi A, Nicholson JK. Intestinal ischemia/reperfusion injury: defining the role of the gut microbiome. Biomark Med. 2009. 3: 175-192. https://doi.org/10.2217/bmm.09.11
  13. Korsmeyer SJ. Regulators of cell death. Trends Genet. 1995. 11: 101-105. https://doi.org/10.1016/S0168-9525(00)89010-1
  14. Logan JS. Prospects for xenotransplantation. Curr Opin Immunol. 2000. 12: 563-568. https://doi.org/10.1016/S0952-7915(00)00139-4
  15. MacKenzie DA, Hullett DA, Sollinger HW. Xenogeneic transplantation of porcine islets: an overview. Transplantation 2003. 76: 887-891. https://doi.org/10.1097/01.TP.0000087114.18315.17
  16. Men X, Han S, Gao J, Cao G, Zhang L, Yu H, Lu H, Pu J. Taurine protects against lung damage following limb ischemia reperfusion in the mt by attenuating endoplasmic reticulum stress-induced apoptosis. Acta Orthop. 2010. 81: 263-267. https://doi.org/10.3109/17453671003587085
  17. Nakka VP, Gusain A, Raghubir R. Endoplasmic reticulum stress plays critical role in brain damage after cerebral ischemia/ reperfusion in rats. Neurotox Res. 2010. 17: 189-202. https://doi.org/10.1007/s12640-009-9110-5
  18. Scheepe JR, van den Hoek J, Junemann KP, Alken P. A standardised mini pig model for in vivo investigations of anticholinergic effects on bladder function and salivation. Pharmacol Res. 2007. 55: 450-454. https://doi.org/10.1016/j.phrs.2007.02.002
  19. Schroder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem. 2005. 74: 739-789. https://doi.org/10.1146/annurev.biochem.73.011303.074134
  20. Susnow N, Zeng L, Margineantu D, Hockenbery DM. Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol. 2009. 19: 42-49. https://doi.org/10.1016/j.semcancer.2008.12.002
  21. Szegezdi E, Duffy A, O'Mahoney ME, Logue SE, Mylotte LA, O'brien T, Samali A. ER stress contributes to ischemia-induced cardiomyocyte apoptosis. Biochem Biophys Res Commun. 2006. 349: 1406-1411. https://doi.org/10.1016/j.bbrc.2006.09.009
  22. Tong QS, Zheng LD, Tang ST, Jiang GS, Ruan QL, Zeng FQ, Dong JH. Nitrofen suppresses cell proliferation and promotes mitochondria-mediated apoptosis in type II pneumocytes. Acta Pharmacol Sin. 2007. 28: 672-684 https://doi.org/10.1111/j.1745-7254.2007.00552.x
  23. Weston RT, Puthalakath H. Endoplasmic reticulum stress and BCL-2 family members. Adv Exp Med Biol. 2010. 687: 65-77. https://doi.org/10.1007/978-1-4419-6706-0_4