동의생리병리학회지 (Journal of Physiology & Pathology in Korean Medicine)

  • 제21권1호
  • /
  • Pages.117-125
  • /
  • 2007
  • /
  • 1738-7698(pISSN)
  • /
  • 2288-2529(eISSN)
대한동의생리학회·한의병리학회 ( The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine)
권호 표지

허혈 상태의 PC12 세포에 대한 대보원전(大補元煎)의 신경보호효과

Neuroprotective Effects of Daebowonjeon on PC12 Cells Exposed to Ischemia

  • 김봉상 (원광대학교 한의과대학 내과학교실) ;
  • 이선우 (원광대학교 한의과대학 내과학교실, 원광대학교 한의학전문대학원) ;
  • 문병순 (원광대학교 한의과대학 내과학교실, 원광대학교 한의학전문대학원)
  • Kim, Bong-Sang (Department of Internal Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Sun-Woo (Department of Internal Medicine, College of Oriental Medicine, Wonkwang University, Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Moon, Byung-Soon (Department of Internal Medicine, College of Oriental Medicine, Wonkwang University, Professional Graduate School of Oriental Medicine, Wonkwang University)
  • 발행 : 2007.02.25
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Neuronal ischemia is a pathological process caused by a lack of oxygen (anoxia) and glucose (hypoglycemia), resulting in neuronal death. It is believed that apoptosis is one of the mechanisms involved in ischemic cell death. Neuronal apoptosis is a process characterized by nuclear DNA fragmentation, changes of plasma membrane organization. To elucidate the mechanism of neuronal death following ischemic insult and to develop neuroprotective effects of Daebowonjeon(DBWJ) against ischemic damage, in vitro models are used. In vitro models of cell death have been devloped with pheochromocytoma (PC12) cell, which have become widely used as neuronal models of oxidative stress, trophic factor, serum deprivation and chemical hypoxia. Using a special ischemic device and PC12 cultures, we investigated an in vitro model of ischemia based on combined Oxygen and Glucose Deprivation (OGD) insult, followed by reoxygenation, mimicking the pathological conditions of ischemia. In this study, Daebowonjeon rescued PC12 cells from Oxygen-Glucose Deprivation (OGD)-induced cell death in a dose-dependent manner The nuclear staining of PC12 cells clearly showed that DBWJ attenuated nuclear condensation and fragmentation which represent typical neuronal apoptotic characteristics. DBWJ also prevents the LDH release and induction of Hypoxia Inducing Factor (HIF)-1 by OGD-exposed PC12 cells. Furthermore, DBWJ reduced the activation of polyADP-ribose polymerase (PARP) by OGO-exposed PC12 cells. These results suggest that apoptosis is an important characteristic of OGD-induced neuronal death and that oriental medicine, such as DBWJ, may prevent PC12 cell from OG D-induced neuronal death by inhibiting the apoptotic process.

키워드

참고문헌

  1. Tabakman, R., Lazarovici, P., Kohen, R. Neuroprotective effects of carnosine and homocarnosine on pheochromocytoma PC12 cells exposed to ischemia. J. Neurochem. Res., 68:463-469, 2002
  2. Peter, L. Ischemia cell death in brain neurons. Physiol. Review, 70:1499, 1999
  3. 崔恩禎. Mongolian Gerbil의 Reversible forebrain ischemia 모델에 미치는 補陽還五湯의 효과, 동의대학교 대학원, 1999
  4. Tabakman, R., Jiang, H., Levine, R.A., Kohen, R. and Lazarovici, P. Apoptotic characteristics of cell death and the neuroprotective effect of Homocarnosine on Pheochromocytoma PC12 cells exposed to ischemia. J. of Neuroscience Res,. 75:499-507, 2004 https://doi.org/10.1002/jnr.20008
  5. Rukenstein, A., Rydel, R.E., Greene, L.A. Multiple agents rescue PC12 cells from serum-free cell death by translation- and transcription-independent mechanisms. J. Neurosci., 11:2552-2563, 1991 https://doi.org/10.1523/JNEUROSCI.11-08-02552.1991
  6. Jin, K.L., Mao, X.O., Nagayama, T., Goldsmith, P.C., Greenberg, D.A. Induction of vascular endothelial growth factor and hypoxia-inducible factor-1${\alpha}$ by global ischemia in rat brain. Neuroscience, 99:577-585, 2000 https://doi.org/10.1016/S0306-4522(00)00207-4
  7. Brunelle, J.K. and Chandel, N.S. Oxygen deprivation induced cell death:An update. Apoptosis, 7:475-482, 2002 https://doi.org/10.1023/A:1020668923852
  8. 張介賓. 張氏景岳全書, 서울, 杏林書院, p 99, 1975
  9. 張介賓著, 김영남 譯. 國譯景岳全書(보급판), 서울, 一中社, pp 15-16, 1993
  10. 劉蘭芳 主編. 中藥湯劑 臨床新用途, 北京, 人民軍醫出版社, p 54-55
  11. Choi, D.W., Maulucci-Gedde, M.A., Kriegstein, A.R. Glutamate neurotoxicity in cortical cell culture. J. Neurosci., 7:357-368, 1987 https://doi.org/10.1523/JNEUROSCI.07-02-00357.1987
  12. Coyle, J.T. and Puttfarecken, P. Oxidative stress, glutamate and neurodegenerative disorders. Science, 262:689-695, 1993 https://doi.org/10.1126/science.7901908
  13. Behl, C. Apoptosis and Alzheimer's disease. J Neural Transm, 107:1325-1344, 2000 https://doi.org/10.1007/s007020070021
  14. Kirino, T., Tamura, A., Sano, K. Selective vulnerability of the hippocampus to ischemia reversible and irreversible types of ischemic cell damage. Progress in Bain Res, 63:39-58, 1985
  15. Banasiak, K.J., Xia, Y., Haddad, G.G. Mechainsms underlying hypoxia-induced neuronal apoptosis. Prog Neurobiol, 62:215-249, 2000
  16. 趙漢栢. 大補元煎이 卵巢摘出로 骨多孔이 誘發된 白鼠에 미치는 影響. 원광대학교 대학원, 1998
  17. 전연이, 박치상, 박창국 등. 당귀의 허혈성 뇌손상 억제작용 및 신경세포 보호효과. 대한본초학회지, 18(4)
  18. 백일성, 박치상, 박창국. 천궁의 허혈성 뇌손상 억제작용 및 신경세포 보호효과. 대한본초학회지, 18(4), 2003
  19. 崔哲源. PC12 세포의 Apoptosis에 대한 星香正氣散의 防禦效果 및 作用機轉 硏究. 원광대학교 대학, 1999
  20. 金鐘吉. 補陽還五湯이 營養血淸缺乏에 의한 PC12 細胞의 枯死에 미치는 영향. 원광대학교 대학원, 2000
  21. 林俊植. 還少丹이 營養血淸 缺乏性 PC12細胞의 Apoptpsis에 미치는 影響. 원광대학교 대학원, 2000
  22. 신민교. 원색 임상본초학, 서울, 남산당, pp 166-167, 171-172, 175-177, 198-199, 219, 221-223, 243-245, 1988
  23. 彭忑仁. 主編. 中華名醫方劑大全, 北京, 金盾出版社出版總發行, pp 56-57, 1995
  24. 裵元植. 最新韓方臨床學, 서울, 南山堂, p 881, 1994
  25. Aizenman, Y., de Velliss, J. Brain neurons develop in a serum and glucose free environment : effect of transferrin, insulin, insulin-like growth factor-I and thyroid hormone on neuronal survival, growth and differentiation, Brain Res., 406:32-42, 1987 https://doi.org/10.1016/0006-8993(87)90766-9
  26. Aruoma, O.L., Halliwell, B., Hoey, B.M. and Butler, J. The antioxidant action of N-acetylcysteine : its reaction with hydrogen peroxide, hydroxyl radical, superoxide and hypochlorous acid. Free Radic. Biol. Med., 6:593-597, 1989 https://doi.org/10.1016/0891-5849(89)90066-X
  27. Savitz, S.I., Rosenbaum, D.M. Apoptosis in neurological disease. J. Neurosurgery, 42:555-574, 1998 https://doi.org/10.1097/00006123-199803000-00026
  28. Greene, LA. and Tischler, A.S. PC12 pheochromocytoma cells in neurobiological research. Adv. Cell Neurobiol., 3:373-414, 1982
  29. 洪元植. 中國醫學史, 서울, 東洋硏究院, pp 335-336, 1987
  30. Lim, M.L., Lum, M.G., Hansen, T.M., Roucou, X., Nagley, P. On the release of cytochrome c from mitochondria during cell death signaling. J. Biomed. Sci., 9:488-506, 2002
  31. Murphy, T.H., M. Miyamoto, A. Sastre, R.L. Schnaar and J.T. Coyle : Glutamate toxicity in a neuronal cell line involves inhibition of cysteine transport leading to oxidative stress. Neuron, 2:1547-1548, 1989 https://doi.org/10.1016/0896-6273(89)90043-3
  32. Ozyurt, E., Graham, D.I., Woodruff, G.N., McCulloch, J. Protective effect of the glutamate antagonit. MK-801 in focal cerebral ischemia in the cat, J. Cereb. Blood Flow Metab., 8:138-143, 1988 https://doi.org/10.1038/jcbfm.1988.18
  33. Jiang, Z., Zhang, Y., Chen, Y., Lam, P.Y., Yang, H., Xu, Q., Yu, A.C. Activation of ERK and Akt in astrocytes under ischemia. Biochem Biophys Res Commun, 294:726-733, 2002 https://doi.org/10.1016/S0006-291X(02)00540-5
  34. Kohen, R., Yamamoto, Y., Cundy, K.C., Ames, B.N. Antioxidant activity of carnosine, homocarnosine and anserine present in muscle and brain. Proc. Natl. Acad. Sci. USA, 85:3175-3179, 1988
  35. Cowan, K.J., and Storey, K.B. Mitogen-activated protein kinases : new signaling pathways functioning in cellular responses to environmental stress. J. Exp. Biol., 206:1107-1115, 2003 https://doi.org/10.1242/jeb.00220
  36. Nicole, M.J., and Bergeron, M. Hypoxia Preconditioning Induces changes in HIF-1 target genes in Neonatal Rat Brain. J. Cerebral Blood Flow and 18. Savitz SI., Rosenbaum DM. Apoptosis in neurological disease. J. Neurosurgery, 42:555-574, 1998 https://doi.org/10.1097/00006123-199803000-00026
  37. Lambeng, N., Willaime-Moraw, S., Mariani, J., Ruberg, M., Brugg, B. Activation of mitogen-activated protein kinase pathway during the death of PC12 cells is dependent on the state of differentiation. Brain Res Mol Brain Res, 111:52-60, 2003 https://doi.org/10.1016/S0169-328X(02)00669-1
  38. Saikumar, P., Dong, Z., Patel, Y., Hall, K., Hopfer, U., Weinberg, J.M., Venkatachalam, M.A. Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene, 17:3401-3415, 1998 https://doi.org/10.1038/sj.onc.1202590
  39. Buttke, T.M., and Sandatrom, P.A. Oxidative stress as a mediator of apoptosis. Immunol. Today., 15:7-10, 1994 https://doi.org/10.1016/0167-5699(94)90018-3
  40. Takeda, H., Tsuji, M., Matsumiya, T. Formation mechanisms of stress adaptation : role of functional coupling of glucocorticoids and brain serotonergic nervous system. Nihon Shinkei Seishin Yakurigaku Zasshi, 20(3):83-91, 2000
  41. Li, Y.F., and Luo, Z.P. Protection of buspirone on the cultured PC12 cells lesioned by corticosterone. Chin J Pharmacol Toxicol, 15(5):333-336, 2001
  42. 鄭普燮, 辛民敎. 圖解 鄕藥(生藥)大事典, 서울, 永林社, pp 407-408, 418-419, 523-524, 632-664, 1034-1035, 1990