생명과학회지 (Journal of Life Science)

  • 제17권1호
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  • Pages.12-17
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  • 2007
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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Curcumin의 전처리는 excitotoxin에 의한 세포사멸로부터 해마신경세포를 보호

Pretreatment of curcumin protects hippocampal neurons against excitotoxin-induced cell death

  • 김소정 (부산대학교 약학대학 약학과, 신약개발연구소, 장수생명과학기술연구원) ;
  • 김근호 (부산대학교 약학대학 약학과, 신약개발연구소, 장수생명과학기술연구원) ;
  • 공경혜 (부산대학교 약학대학 약학과, 신약개발연구소, 장수생명과학기술연구원) ;
  • 이재원 (부산대학교 약학대학 약학과, 신약개발연구소, 장수생명과학기술연구원)
  • Kim, So-Jung (Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University) ;
  • Kim, Keun-Ho (Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University) ;
  • Kong, Kyoung-Hye (Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University) ;
  • Lee, Jae-Won (Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University)
  • 발행 : 2007.01.29
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초록

Curcumin은 자연에 존재하는 황색의 페놀성분의 커리 향신료이며 항산화 및 항염증의 성질을 가지고 있어서 산화 스트레스와 면역염증과 관련한 여러 질병의 치료로 사용되어져 왔다. 이러한 curcumin의 항산화 및 항염증 효과는 여러 퇴행성 신경질환으로부터 뇌를 보호하는데 유용하게 적용될 수 있다. 본 연구에서는 glutamate에 의한 excitotoxicity로부터 해마신경세포를 보호하는 curcumin의 신경보호효과에 대하여 보고한다. 태아 생쥐의 해마로부터 얻어진 신경세포를 저농도의 curcumin으로 전처리한 경우, 신경세포는 glutamate에 의한 세포사멸로부터 보호되었다. 그러나 이러한 신경보호효과는 산화스트레스의 조절과는 무관하였다. 흥미롭게도 고농도의 curcumin전처리는 오히려 초대배양 신경세포의 세포사멸을 유도하였다. 해마신경세포에서 스트레스 반응 단백질인 HSP70이 저농도의 curcumin을 처리하였을 때 현저하게 증가하였으며 반면 세포사멸의 마커인 절단된 PARP의 양은 고농도의 curcumin을 처리하였을 때 급증함이 immunoblot분석을 통하여 관찰되었다. 이러한 발견은 curcumin이 excitotoxin인 glutamate에 대한 신경세포의 반응을 조절할 수 있음을 보여주고 curcumin과 관련 화합물들의 퇴행성 신경질환에서의 예방 및 치료법으로의 가능성을 제시하고 있다.

Curcumin is a natural phenolic yellow curry spice, derived from the tumeric, which has been used for the treatment of diseases associated with oxidative stress and inflammation. Curcumin is known to have both anti-oxidative and anti-inflammatory properties. These properties can be beneficial to protect the brain from the neurodegenerative diseases. We now report the neuroprotective effects of curcumin pretreatment in primary hippocampal neurons to glutamate-induced excitotoxicity. Pretreatment of embryonic mouse hippocampal cell cultures with low does of curcumin protected neurons against glutamate-induced death, however, this neuroprotection was not correlated with the modulation of oxidative stress. Interestingly, high dose of curcumin showed the cytotoxicity in primary cultured hippocampal neurons. Immunoblot analyses showed that levels of stress response. protein HSP70 were significantly elevated in neurons exposed to low dose of curcumin, whereas levels of cleaved PARP were increased in neurons exposed to high dose of curcumin. These findings show that curcumin can modulate neuronal responses to glutamate, and suggest possible use of curcumin and related compounds in the prevention and/or treatment of neurodegenerative disorders.

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참고문헌

  1. Abe, Y., S. Hashimoto and T. Horie. 1999. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 39, 41-47 https://doi.org/10.1006/phrs.1998.0404
  2. Aggarwal, B. B., A. Kumar and A. C. Bharti, 2003. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23, 363-398
  3. Arundine, M. and M. Tymianski. 2003. Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium 34, 325-337 https://doi.org/10.1016/S0143-4160(03)00141-6
  4. Atsumi, T., Y. Murakami, K. Shibuya, K. Tonosaki and S. Fujisawa. 2005. Induction of cytotoxicity and apoptosis and inhibition of cyclooxygenase-2 gene expression, by curcumin and its analog, alpha-diisoeugenol. Anticancer Res 25, 4029-4036
  5. Das, K. C. and C. K. Das. 2002. Curcumin (diferuloylmethane), a singlet oxygen ((1)O(2)) quencher. Biochem Biophys Res Commun 295, 62-66 https://doi.org/10.1016/S0006-291X(02)00633-2
  6. Frautschy, S. A., W. Hu, P. Kim, S. A. Miller, T. Chu, M. E. Harris-White and G. M. Cole, 2001. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 22, 993-1005 https://doi.org/10.1016/S0197-4580(01)00300-1
  7. Ganguli, M., V. Chandra, M. I. Kamboh, J. M. Johnston, H. H. Dodge, B. K. Thelma, R. C. Juyal, R. Pandav, S. H. Belle and S. T. DeKosky. 2000. Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study. Arch Neurol 57, 824-830 https://doi.org/10.1001/archneur.57.6.824
  8. Hudspith, M. J. 1997. Glutamate: a role in normal brain function, anaesthesia, analgesia and CNS injury. Br J Anaesth 78, 731-747 https://doi.org/10.1093/bja/78.6.731
  9. Kim, H. J., K. W. Kim, B. P. Yu and H. Y. Chung. 2000. The effect of age on cyclooxygenase-2 gene expression: NF-kappaB activation and IkappaBalpha degradation. Free Radic BioI Med 28, 683-692 https://doi.org/10.1016/S0891-5849(99)00274-9
  10. Korosbetz, W. J. and J. V. Bonventre. 1994. Heat shock response in the central nervous system. Experientia 50, 1085-1091 https://doi.org/10.1007/BF01923465
  11. Lee, J., A. J. Bruce-Keller, Y. Kruman, S. L. Chan and M. P. Mattson, 1999. 2-Deoxy-D-glucose protects hippocampal neurons against excitotoxic and oxidative injury: evidence for the involvement of stress proteins. J Neurosci Res 57, 48-61 https://doi.org/10.1002/(SICI)1097-4547(19990701)57:1<48::AID-JNR6>3.0.CO;2-L
  12. Lee, J., S. L. Chan, C. Lu, M. A. Lane and M. P. Mattson. 2002. Phenformin suppresses calcium responses to glutamate and protects hippocampal neurons against excitotoxicity. Exp Neurol 175, 161-167 https://doi.org/10.1006/exnr.2002.7864
  13. Liontas, A. and H. Yeger. 2004. Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma. Anticancer Res 24, 987-998
  14. Liu, Y., H. Kato, N. Nakata and K. Kogure. 1993. Temporal profile of heat shock protein 70 synthesis in ischemic tolerance induced by preconditioning ischemia in rat hippocampus. Neuroscience 56, 921-927 https://doi.org/10.1016/0306-4522(93)90138-6
  15. Lodha, R. and A. Bagga. 2000. Traditional Indian systems of medicine. Ann Acad Med Singapore 29, 37-41
  16. Lowenstein, D. H, P. H. Chan and M. F. Miles. 1991. The stress protein response in cultured neurons: characterization and evidence for a protective role in excitotoxicity. Neuron 7, 1053-1060 https://doi.org/10.1016/0896-6273(91)90349-5
  17. Lowenstein, D. H., R. P. Gwinn, M. S. Seren, R. P. Simon, and T. K. Mclntosh. 1994. Increased expression of mRNA encoding calbindin-D28K, the glucose-regulated proteins, or the 72 kDa heat-shock protein in three models of acute CNS injury. Brain Res Mol Brain Res 22, 299-308 https://doi.org/10.1016/0169-328X(94)90058-2
  18. Matteucci, A., C. Frank, M. R. Domenici, M. Balduzzi, S. Paradisi, G. Carnovale-Scalzo, G. Scorcia and F. Malchiodi-Albedi. 2005. Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on N-methyl-D: -aspartate-induced intracellular Ca(2+) increase. Exp Brain Res 167, 641-648 https://doi.org/10.1007/s00221-005-0068-0
  19. Mattson, M. P., M. Murrain, P. B. Guthrie and S. B. Kater. 1989. Fibroblast growth factor and glutamate: opposing roles in the generation and degeneration of hippocampal nenroarchitecture. J Neurosci 9, 3728-3740 https://doi.org/10.1523/JNEUROSCI.09-11-03728.1989
  20. Mattson, M. P., H. Wang and E. K. Michaelis. 1991. Developmental expression, compartmentalization and possible role in excitotoxicity of a putative NMDA receptor protein in cultured hippocampal neurons. Brain Res 565, 94-108 https://doi.org/10.1016/0006-8993(91)91740-R
  21. Nicholson, D. W., A. Ali, N. A. Thornberry, J. P. Vaillancourt, C. K. Ding, M. Gallant, Y. Gareau, P. R. Griffin, M. Labelle, Y. A. Lazebnik and et al. 1995. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376, 37-43 https://doi.org/10.1038/376037a0
  22. Ono, K., K. Hasegawa, H. Naiki and M. Yamada. 2004. Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res 75, 742-750 https://doi.org/10.1002/jnr.20025
  23. Pang, Z. and J. W. Geddes. 1997. Mechanisms of cell death induced by the mitochondrial toxin 3-nitro-propionic acid: acute excitotoxic necrosis and delayed apoptosis, J Neurosci 17, 3064-3073 https://doi.org/10.1523/JNEUROSCI.17-09-03064.1997
  24. Sattler, R. and M. Tymianski. 2000. Molecular mechanisms of calcium-dependent excitotoxicity. J Mol Med 78, 3-13 https://doi.org/10.1007/s001090000077
  25. Scapagnini, G., C. Colombrita, M. Amadio, V. D' Agata, E. Arcelli, M. Sapienza, A. Quattrone and V. Calabrese. 2006. Curcumin activates defensive genes and protects neurons against oxidative stress. Antioxid Redox Signal 8, 395-403 https://doi.org/10.1089/ars.2006.8.395
  26. Su, C. C., G. W. Chen, J. G. Lin, L. T. Wu and J. G. Chung. 2006. Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B /p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions. Anticancer Res 26, 1281-1288
  27. Yang, F., G. P. Lim, A. N. Begum, O. J. Ubeda, M. R. Simmons, S. S. Ambegaokar, P. P. Chen, R. Kaved, C. G. Glabe, S. A. Frautschy and G. M. Cole. 2005. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques and reduces amyloid in vivo. J Biol Chem 280, 5892-5901 https://doi.org/10.1074/jbc.M404751200
  28. Yu, Z., H. Luo, W. Fu and M. P. Mattson. 1999. The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol 155, 302-314 https://doi.org/10.1006/exnr.1998.7002