Journal of Oral Medicine and Pain

  • 제33권3호
  • /
  • Pages.247-256
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  • 2008
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  • 2288-9272(pISSN)
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  • 2383-8493(eISSN)
대한안면통증구강내과학회 (Korean Academy of Orofacial Pain and Oral Medicine)
권호 표지

구속 스트레스에 의한 타액선 조직내의 Clusterin 발현

Expression of Clusterin in the Salivary Gland under Restraint Stress

  • 박희경 (경희대학교 치의학전문대학원 구강내과학교실) ;
  • 전양현 (경희대학교 치의학전문대학원 구강내과학교실) ;
  • 홍정표 (경희대학교 치의학전문대학원 구강내과학교실) ;
  • 어규식 (경희대학교 치의학전문대학원 구강내과학교실)
  • Park, Hee-Kyung (Department of Oral Medicine, School of Dentistry, Kyung Hee University) ;
  • Chun, Yang-Hyun (Department of Oral Medicine, School of Dentistry, Kyung Hee University) ;
  • Hong, Jung-Pyo (Department of Oral Medicine, School of Dentistry, Kyung Hee University) ;
  • Auh, Q-Schick (Department of Oral Medicine, School of Dentistry, Kyung Hee University)
  • 발행 : 2008.09.30
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초록

일상생활에서 우리는 항상 스트레스에 노출되어 있으며, 스트레스에 대한 반응은 우리 삶의 질과 건강에 중요한 영향을 미친다. 특히 정서적으로 중요한 구강안면영역에도 다양한 스트레스성 질환이 존재한다. 그러나 스트레스와 질병에 관한 오랜 연구에도 불구하고 스트레스성 구강안면질환의 병인은 아직 명확하지 않다. 이에 저자는 최근 임상의학에서 관심이 집중되어지고 있는 스트레스와 질병에 대한 분자생물학적 접근의 일환으로 스트레스성 구강안면질환의 병인을 규명하고자 본 연구에 임하였다. 즉, 스트레스 단백질로 알려진 clusterin이 스트레스의 생리적 반응으로서 세포보호작용 결과 발현된다는 사실에 기초하여, 스트레스 부여 후 타액선 조직 내에서의 그 발현변화를 추적하였다. Sprague-Dawley계 웅성 백서(200-230g/bw)를 구속 스트레스 부여군(구속장치에 구속한 후 0, 3, 5일에 희생) 및 정상군으로 나누고, 각각 악하선을 적출하였으며, 면역조직화학법 및 Northern Blot을 이용하여 Clusterin의 변화를 관찰하였다. 그 결과는 다음과 같다. 1. 구속 스트레스 부여군의 clusterin 단백질은 실험 즉일군에서 증가되었고, 그 이후에는 감소되었다. 2. 구속 스트레스 부여 3일군과 5일군에서 핵붕괴 및 핵농축 등의 핵변화를 동반한 apoptosis가 유도되었다. 3. 구속 스트레스 부여 결과, 선포세포가 도관세포보다 일찍 세포사하였다. 4. 구속 스트레스 부여군의 clusterin mRNA는 실험 즉일군에서만 미약하게 관찰되었다. 즉, 타액선 조직은 스트레스 단백질인 clusterin을 생산하여 세포를 보호함으로써 스트레스 상황에 적응하지만, 생리적 적응한계를 넘는 스트레스에 노출될 때에는 조직이 apoptosis됨이 확인되었다. 따라서, 본 연구결과는 구강건조증등 스트레스성 타액선관련 증상 및 질환의 병리적 기전에 대한 규명에 도움이 되리라고 생각하며, 또한 clusterin은 향후 생체에 가해진 스트레스에 대한 표식자(marker)로 사용될 수 있을 것으로 사료된다.

The belief that stress leads to illness has a long history. A number of the orofacial disease are also closely associated with stress. Despite research in the relationship of stress and the orofacial diseases leading to statistically significant correlations, the pathology remains vague. In the present study, the expression of clusterin, a stress protein responsible for antiapoptosis and cytoprotection, under restraint stress condition was observed in the submandibular gland, one of the major salivary glands. Sprague-Dawley rats were divided into 2 groups: normal group and restraint stress group. The rats of restraint stress group were placed in the stress cages and then sacrificed at day 0, 3 and 5 day of the experiment. After that, the submandibular glands of all the rats were excised immediately. The levels of clusterin proteins and mRNA in the tissues were measured by immunohistochemistry and Northern blot analyses, respectively. The results were as follows: 1. In the immunohistochemistry, clusterin protein was detected only immediately after the application of restraint stress. 2. In the restraint stress group, at day 3 and 5, histologically apoptosis was induced with karyorrhectic and pyknotic changes. 3. By the restraint stress, acinic cells were destructed earlier than ductal cells. 4. In the Northern blot, mRNA of clusterin was expressed only immediately after the application of restraint stress. The overall results suggest that as an early response to stress, clusterin is expressed in the glands to protect the glandular cells from the stress. But if stress is so strong and prolonged that it can exceed the stress adaptability of the cells, then the cells may undergo apoptosis instead of producing clusterin. An Epidemiologic Study of Symptoms of Temporomandibular Disorders in Korean College Students.

키워드

참고문헌

  1. Kutash IL, Schlesinger L.B. Handbook of stress and anxiety. California, 1980, Jossey-Bass Inc., pp. 144-158
  2. Hinkle LE Jr. Stress and diseases; the concept after 50 years. Soc Sci Med 1987;25(6):561-566 https://doi.org/10.1016/0277-9536(87)90080-3
  3. Selye H. Selye's guide to stress research. Vol. I, Canada, 1980, Van Nostrand Reinhold Ltd., pp. 46-70
  4. Frankenhaeuser M, Lundberg U. Sympathetic-adrenal and pituitary-adrenal response to challenge. Psychiatry. Vol. 2, London, 1985, Plenum Press, pp. 699-704
  5. Contran RS, Kumar V, Robbins SL, Schoen FJ. Robbins pathologic basis of disease. 5th Ed., Philadelphia, 1994, W.B. Saunders Co., pp. 51-92
  6. Steven A, Lowe J. Pathology. London, 1995, Mosby, pp. 177-214
  7. Shklar G, McCarthy PL. The oral manifestations of systemic disease. Boston and London, 1976, Butterworths, pp. 74-81
  8. Fritz JB, Murphy B. Insight into a multifunctional protein. TEM 1993;4(2):41-45
  9. Purello M, Betuzzi S, Di Pietro C et al. The gene for SP-40,40, human homologue of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostatic messenger 2, maps to chromosome 8. Genomics 1991;10:151-156 https://doi.org/10.1016/0888-7543(91)90495-Z
  10. Jenne DE, Tschopp J. Molecular structure and functional characterization of a human complement cytolysis inhibitor found in blood and seminal plasma: identity to sulfated glycoprotein 2, a constituent of rat testis fluid. Proc Natl Acad Sci USA 1989;86(71):23-27
  11. Michel D, Chatelanin G, North S, Brun G. Stress-induced transcription of the clusterin/apoJ gene. Biochem J 1997;328:45-50 https://doi.org/10.1042/bj3280045
  12. Jordan-Starck TC, Witte DP, Aronow BJ, Harmony JAK. Apolipoprotein J : a membrane policeman? Curr Opin Lipidol 1992;3:75-85 https://doi.org/10.1097/00041433-199204000-00004
  13. McGeer PL, Kawamata T, Walker DG. Distribution of clusterin in Alzheimer brain tissue. Brain Res 1992;579:337-341 https://doi.org/10.1016/0006-8993(92)90071-G
  14. Laskins J, Bennett SAL, Chen JH et al. Clusterin biogenesis is altered during apoptosis in the regressing rat ventral prostate. J Biol Chem 1998;273:27887-27895 https://doi.org/10.1074/jbc.273.43.27887
  15. Aronow BJ, Lumd SD, Brown TL. Apolipoprotein J expression at fluid-tissue interfaces: potential role in barrier cytoprotection. Proc Natl Acad Sci USA 1993;90:725-729 https://doi.org/10.1073/pnas.90.2.725
  16. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1980;29:577-580
  17. Chomezynski P, Sacchi N. Single step method for RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:166-169
  18. Weiss JM. Psychological factors in stress and diseases. Sci Am 1972;226:104-113
  19. Cohen S, Wills TA. Stress, social support, and the buffering hypothesis. Psycho Bulletin 1985;98:310-357 https://doi.org/10.1037/0033-2909.98.2.310
  20. Lundberg U. Methods and applications of stress research. Kor J Stress Res 1994;2(1):13-33
  21. Tomei LD, Kiecolt-Glaser JK, Kennedy S, Glaser R. Psychological stress and phorbol ester inhibition of radiation-induced apoptosis in human peripheral blood leukocytes. Psychiatry Res 1990;33:59-71 https://doi.org/10.1016/0165-1781(90)90149-Y
  22. Duke RC, Chervenak R, Chgen JJ. Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc Natl Acad Sci USA 1983;80:6361-6365 https://doi.org/10.1073/pnas.80.20.6361
  23. Depue RA, Monroe SM. Conceptualization and measurement of human disorder in life stress research: the problem of chronic disturbance. Psycho Bull 1986;99:36-51 https://doi.org/10.1037/0033-2909.99.1.36
  24. Lipowski ZJ. Psychiatry of somatic disease: epidemiology, pathogenesis, classification. Comprehen Psychi 1975;16:105-124 https://doi.org/10.1016/0010-440X(75)90056-5
  25. Chun YH, Hong JP. Stress and orofacial diseases. Kor J Stress Res 1995;3(1):57-72
  26. Borland LR. Odontophobia-Inordinate fear of dental treatment. Dent Clin N Am 1962;6:683-695
  27. Dobrosielski-Vergona K. Biology of the salivary glands. Boca Raton, 1993, CRC Press Inc., pp. 431-441
  28. Rankow RM, Polayes IM. Diseases of the salivary glands. Philadelphia, 1980, W.B. Saunders Co., pp. 41-51
  29. Field EA, Longman LP, Bucknall R et al. The establishment of a xerostomia clinic: a prospective study. Br J Oral Maxillofac Surg 1997;35(2):96-103 https://doi.org/10.1016/S0266-4356(97)90683-5
  30. Sreebny LM. Recognition and treatment of salivary induced conditions. Int Den J 1989;39:197-204
  31. Lynch MA, Brightman VJ, Greenber MS. Burket's oral medicine. 9th Ed., philadelphia, 1994, J.B. Lippincott Co., pp. 487-509
  32. Lewis MA, Lamey PJ. Clinical oral medicine. Oxford, 1993, Wright, pp. 1850-1854
  33. de Silva HV, Harmony JAK, Stuart WD, Gil CM, Robbins J. Apoprotein J-structure and tissue distribution. Biochem 1990;29:5380-5389 https://doi.org/10.1021/bi00474a025
  34. de Silva HV, Stuart WD, Park YB. Purification and characterization of apolipoprotein J. J Biol Chem 1990;265:14292-14297
  35. de Silva HV, Stuart WD, Duvic CR. A 70kDa apolipoprotein designated apoJ is a marker for subclasses of human plasma high density lipoproteins. J Biol Chem 11990;265:13240-13247
  36. Leger JG, Montnetit ML, Tenniswood MP. Characterization and cloning of androgen-repressed mRNAs from rat ventral prostate. Bio-chem Biophys Res Commun 1987;147:196-203 https://doi.org/10.1016/S0006-291X(87)80106-7
  37. Silkensen JR, Skubitz KM, Skubitz AP. Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells. J Clin Invest 1995;96(6):2646-2653 https://doi.org/10.1172/JCI118330
  38. Min BH, Jeong WY, Kang SW et al. Transient expression of clusterin (sulphated glycoprotein-2) during development of rat pancreas. J Endocrinol 1998;158:43-52 https://doi.org/10.1677/joe.0.1580043
  39. O'Bryan MK, Cheema SS, Bartlett PF, Murphy BF. Clusterin levels increase during neuronal development. J Neurobiol 1993;24(4):421-32 https://doi.org/10.1002/neu.480240402
  40. Koch-Brandt C, Morgans C. Clusterin: a role in cell survival in the face of apoptosis? Prog Mol Subcell Biol 1996;16:130-149
  41. Nishida K, Kawasaki S, Adachi W, Kinoshita S. Apolipoprotein J expression in human ocular surface epithelium. Ophthalmol Vis Sci 1996;37:2285-2292
  42. Sensibar JA, Sutkowski DM, Raffo A et al. Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). Cancer Res 1996;55(11):2431-1437
  43. Swertfeger DK, Witte DP, Stuart WD, Rockman HA, Harmony JAK. Apolipoprotein J/clusterin induction in myocarditis. Am J Pathol 1996;148(6):1971-1983
  44. Ahuja HS, Tenniswood MT, Lockshin R, Zakeri Z. Expression of clusterin in cell differentiation and cell death. Biochem Cell Biol 1994;72:523-530 https://doi.org/10.1139/o94-070
  45. Clark AM, Griswold MD. Expression of clusterin/sulfated glycoprotein-2 under condition of heat stress in rat sertoli cells and a mouse sertoli cell line. J Androl 1997;8(3):257-263
  46. Chung WB, Cho HG, Hong JP. The expression of clusterin(SGP-2) to the stress on the salivary glands of rats. J Kor Acad Oral Med 1997;22(2):395-408