영양혈청 결핍성 PC12 세포고사에서 HO-1의 발현 증가를 통한 환소단의 보호 효과

Protective Effect of Hwansodan in Serum and Glucose Deprivation Induced-apoptotic Death of PC12 Cells Via Ho-1 Expression

  • 정재은 (원광대학교 한의과대학 심계내과학교실) ;
  • 김진경 (원광대학교 의과대학 미생물학교실) ;
  • 강백규 (원광대학교 한의과대학 심계내과학교실) ;
  • 박찬희 (원광대학교 의과대학 미생물학교실) ;
  • 박래길 (원광대학교 의과대학 미생물학교실) ;
  • 문병순 (원광대학교 한의과대학 심계내과학교실)
  • Jung, Jae-Eun (Department of internal Medicine, School of Oriental Medicine) ;
  • Kim, Jin-Kyung (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Kang, Baek-Gyu (Department of internal Medicine, School of Oriental Medicine) ;
  • Park, Chan-Ny (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Park, Rae-Kil (Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Moon, Byung-Soon (Department of internal Medicine, School of Oriental Medicine)
  • 발행 : 2006.12.25

초록

The water extract of Hwansodan has been traditionally used for treatment of ischemic brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of Hwansodan rescues cells from neurodegenerative disease. PC12 pheochromocytoma cells have been used extensively as a model for studying the cellular and molecular mechanisms of neuronal cell damages. Under deprivation of growth factor and ischemic injury, PC12 cells spontaneously undergoes apoptotic cell death. Serum and glucose deprivation markedly decreased the viability of PC12 cells, which was characterized with apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the aqueous extract of Hwansodan significantly reduced serum and glucose deprivation-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Pretreatment of Hwansodan also ingibited the activation of caspase-3, in turn, degradation of ICAD/DFF45 was completely abolished in serum and glucose deprivated cells. Furthermore, pretreatment of Hwansodan obviously increased heme oxygenase 1 (HO-1) expression in PC12 cells. Taken together, the data suggest that the protective effects of Hwansodan against serum and glucose deprivation induced oxidative injuries may be achieved through the scavenging of reactive oxygene species accompanying with HO-1 induction.

키워드

참고문헌

  1. 王昻.. 北京. 中國中醫葯出版社, 1997
  2. 서원희. 환소단이 뇌조직의 산화작용에 미치는 영향. 대전, 대전대 대학원, 1998
  3. 임준식. 환소단이 영양쳘성 결핍성 PC12 신경세포의 apoptosis에 미치는 영향. 익산, 원광대 한의학 전문대학원, 2000
  4. 金賢兒. 老人性 痴呆에 대한 文獻的 考察. 大韓韓方內科學會誌 13(2):57-68, 1992
  5. 徐政烈 외. 痴呆에 대한 東西醫學의 文獻的 考察. 大韓針灸學會誌 14(1):226-238, 1997
  6. 黃義完 외. 痴呆에 대한 韓醫學的 臨床硏究. 東醫神經精神科學會誌 7(1):1-13, 1996
  7. 姜亨沅. 天門冬에 의한 腦神經膠細胞로부터 炎症性 細胞活性物質 分泌의 抑制 效果. 圓光大學校 大學院 碩士論文, 1997
  8. 김상호 외. 일반병리학 고문사. p.5, 2000. / 대한병리학회. 병리학. 고문사, p 28, 1995
  9. 장양태. 비부과학. 서울, 여문각, pp 23-25, 1994
  10. 리정복. 장수학. 서울, 의성당, pp 41, 64-69, 1987
  11. 박찬국. 장상학. 서울, 일중사, pp 167-168, 1992
  12. 정융주. 도해뇌신경외과학. 서울, 제일의학, p 30, 31, 1992
  13. 지제근. 신경병리학. 서울, 서울대학교출판부, pp 111-115, 1990
  14. 배철영 외. 노인의학. 서울, 고려의학, pp 24-27, 1996
  15. 진선 외. 실용중의뇌병학. 북경, 학원출판사, pp 216, 237-245, 784-797, 1993
  16. 장길. 중의치료뇌위축근황. 천진, 전진중의, 13(1):45-46, 1996
  17. 서순규. 성인병.노인의학. 서울, 고려의학, pp 10-15, 28-30, 225-229, 1992
  18. 김진수. 알츠하이머병의 신경화학적 변화에 관한 고찰. 대한신경과학회지 3(1):46-46, 1985
  19. 종전화. 정의방제통석. 북경, 학원출판사, pp 245-237
  20. 許沛虎 외. 中醫 腦病學. 北京, 中國醫葯科技出版社, p 464, 1998
  21. 崔應珉 외. 腦病. 北京, 河南醫科大學出版社, p 185, 186, 1998
  22. 신민교. 임상본초학. 서울, 영림사, p 248, 185, 525, 260, 274, 649, 209, 646, 280, 225, 305, 227, 221, 604, 176, 2000
  23. 한방약리학 교재편찬위원회. 한방약리학. 서울, 신일상사, pp 682-683, 719-720, 734-735,543-544, 717-718, 49-50, 420-421, 69-70, 307-308, 557-558, 583-584, 691-692, 738-739, 135-136, 2005
  24. Kim, M.S., So, H.S., Park, J.S., Lee, K.M., Moon, B.S., Lee, H.S., Kim, T.Y., Moon, S.K., Park, R. Hwansodan protects PC12 cells against serum-deprivation-induced apoptosis via a mechanism involving Ras and mitogen-activated protein (MAP) kinase pathway. Gen Pharmacol. 34(4):227-235. 2000 https://doi.org/10.1016/S0306-3623(00)00065-3
  25. Gross, A., McDonnell, J.M., Korsmeyer, S.J. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 13: 1899-1911. 1999 https://doi.org/10.1101/gad.13.15.1899
  26. Kroemer, G., Dallaporta, B., Resche-rigon, M. The mitochondrial death/life regulator in apoptosis and necrosis. Nature Med. 6: 614-620. 1998
  27. Reed, J.C. Bcl2 and the regulation of programmed cell death. J. Cell. Biol. 124: 1-6, 1994 https://doi.org/10.1083/jcb.124.1.1
  28. Herr, I., Wilhelm, D., Bohler, T., Angel, P., Debatin, K.M. Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis. EMBO. 16: 6200-6208. 1997 https://doi.org/10.1093/emboj/16.20.6200
  29. Heibein, J.A., Barry, M., Motyka, B., Bleackley, R.C. Granzyme B-induced loss of mitochondrial inner membrane potential (Delta Psi m) and cytochrome c release are caspase independent. J Immunology. 163(9):4683-4693. 1999
  30. Micheau, O., Solary, E., Hammann, A., Martin, F., Dimanche- Boitrel, M.T. Sensitization of cancer cells treated with cytotoxic drugs to fas-mediated cytotoxicity. J Natl Cancer Inst. 89: 783-789, 1997 https://doi.org/10.1093/jnci/89.11.783
  31. Trauth, B.C., Klas, C., Peters, A.M.J, Matzuku, S., Moller, P., Falk, W., Debatin, K.M., Krammer, P.H. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 245: 301-305. 1989 https://doi.org/10.1126/science.2787530
  32. Kim, Y.M., Talanian, R.V., Billiar, T.R. Nitric oxide inhibits apoptosis by preventing increse in caspase-3 like activity via distinct mechanism. J. Biol. Chem. 272: 311-338. 1997 https://doi.org/10.1074/jbc.272.1.311
  33. Andreeva, L., Heads, R., Green, C.J. Cyclophilins and their possible role in the stress response.Int J Exp Pathol. 80(6):305-315. Review. 1999 https://doi.org/10.1046/j.1365-2613.1999.00128.x
  34. Lemos, F.B., Ijzermans, J.N., Zondervan, P.E., Peeters, A.M., Van Den Engel, S., Mol, W.M., Weimar, W., Baan, C.C. Differential expression of heme oxygenase-1 and vascular endothelial growth factor in cadaveric and living donor kidneys after ischemia-reperfusion. J Am Soc Nephrol. 14(12):3278-3287. 2003 https://doi.org/10.1097/01.ASN.0000098683.92538.66