Effect on Alzheimer's Disease by Sesim-tang in CT105-overexpressed SK-N-SH Cell Lines

CT105로 유도된 신경모세포종 세포주에서 세심탕의 항치매 효과

  • 권형수 (대구한의대 한의과대학 심계내과학교실) ;
  • 박치상 (대구한의대 한의과대학 심계내과학교실) ;
  • 박창국 (대구한의대 한의과대학 심계내과학교실)
  • Published : 2004.06.01

Abstract

Objectives : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. Although a variety of oriental prescriptions, including Sesim-tang, have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. The present study investigated the effects of Sesim-tang on apoptotic cell death induced by CT105 (carboxy terminal 105 amino acid peptide fragment of APP) overexpression in SK-N-SH neuroblastoma cell lines. Methods: We studied the regenerative and inhibitory effects on Alzheimer's disease in CT105-induced SK-N-SH cell lines by Sesim-tang water extract. We examined for cell morphological pattern, DNA fragmentation, LDH activity assay, zymography assay, and immunohistochemistric analysis. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. Results: Findings from our experiments have shown that Sesim-tang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in the cell line. In addition, pretreatment with Sesim-tang ($>50\mu\textrm{g}/ml$ for 12 hours) partially prevented CT105-induced cytotoxicity in SK-N-SH cell lines. SK-N-SH cell lines overexpressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase-contrast microscope and LDH activity measurements in the culture media, the CT105-induced cell death was significantly inhibited by Sesim-tang water extract. Sesim-tang was found to reduce the expression of APP and caspase-3 induced by CT105 in SK-N-SH cell lines and in rat hippocampus. Conclusions: As the result of this study, in the Sesim-tang group, apoptosis in the nervous system is inhibited, the repair against the degeneration of SK-N-SH cell lines by CT105 expression is promoted. Hence, Sesim-tang may be beneficial for the treatment of AD.

Keywords

References

  1. 上海中醫藥雜誌 v.3 태종담치 張覺人
  2. 동의생리병리학회지 v.16 no.2 새로운 제형의 치매치료제제의 효능연구 김지현(외)
  3. ICD-10 정신 및 행동장애 분류 李符永(譯)
  4. Nature v.387 no.29 Short precursor shortens memory Mattson, M.P.;Furukawa, K.
  5. Neuroreport v.9 no.17 C-terminal fragment of amyloid precursor protein inhibits calcium uptake into rat brain microsomes by Mg2+-Ca2+ ATPase Kim HS;CH Park;YH Suh
  6. Neuroreport v.10 C-terminal fragment of Alzheimer's amyloid precursor protein inhibits sodium/calcium exchanger activity in SK-N-SK cell Kim HS;Lee JH;Suh YH
  7. 辨證錄 陳士鐸
  8. 實用中醫內科學 黃大東(외)
  9. 동의신경정신과학회지 v.12 no.1 洗心湯에 의한 뇌 별세포로부터 염증성세포활성물질의 분비 억제효과 김태헌;김준한;강형원;유영수
  10. Lancet v.2 Selective loss of cholinergic neurones in Alzheimer's disease Davis, P.;Maloney, A.J.F.
  11. 동의생리병리학회지 v.16 no.5 釣鉤藤이 $\beta$<\TEX>APP 과발현 인간 신경아세포암에서의 항치매효과에 대한 연구 김상호
  12. Mol Med Today v.25 no.1 Molecular pathogenesis of sporadic and familial forms of Alzheimer's disease Ray WJ;Ashall F;Goate AM
  13. 대한신경과학회지 v.3 no.1 Alzheimer's disease의 신경화학적 변화에 관한 고찰 김진수
  14. J Neural Transm v.61 no.Suppl. Beta-amyloid precursor protein. ETS-2 and collagen alpha 1(IV) chain precursor, encoded on chromosome 21, are not overexpressed in fetal Down syndrome : further evidence against gene dosage effect Engidawork E;Baiic N;Fountoulakis M;Dierssen M;Greber-Platzer S;Lubec G
  15. Neurology v.52 no.4 In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease Kuhl DE;Koeppe RA;Minoshima S;Snyder SE;Ficaro EP;Foster NL;Frey KA; Kilbourn MR
  16. Arch Neuropsychiatr v.56 no.313 Treatment of Alzheimer's disease ; critical evaluation of the use of anticholinesterase Almeida OP
  17. J. Neurochem. v.65 no.4 Processing of the beta-amyloid precursor protein and its regulation in Alzheimer's disease Checler F.
  18. J. Neurochem. v.64 no.5 Role of cyclic GMP in the regulation of neuronal calcium and survival by secreted forms of beta-amyloid precursor Barger SW;Fiscus RR;Ruth P;Hofmann F;Mattson MP
  19. Science v.258 no.2057 Production of the Alzheimer amyloid beta protein by normal proteolytic processing Shoji M;Glode TE;Ghiso J;Cheung TT;Estus S;Shaffer LM;Cai XD;McKay DM; Tintner R;Frangione B(et al.)
  20. Neurobiol Aging v.13 no.5 Lack of Alzheimer pathology after beta-amyloid protein injection in rat brain Games D;Khan KM;Soriano FG;Keim PS;Davis DL;Bryant K;Lieberburg I
  21. Neurobiol Aging v.13 no.5 Implants containing beta-amyloid protein are not neurotoxic to young and old rat brain Clemens JA;Stephenson DT
  22. EMBO J. v.7 no.4 Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease Dyrks T;Weidemann A;Multhaup G;Salbaum JM;Lemaire HG;Kang J;Muller-Hill B; Masters CL;Beyreuther K
  23. Brain Res Mol Brain Res. v.26 no.1-2 Cytotoxicity mediated by conditional expression of a carboxyl-terminal derivative of the beta-amyloid precursor protein Sopher BL;Fukuchi K;Smith AC;Leppig KA;Furlong CE;Martin GM
  24. J. Neurochem. v.67 Neurotoxicity of a caroboxy terminal fragment of the Alzheimer's amyloid precursor protein Kim SH;Suh YH
  25. Eur J Biochem. v.225 Familial Alzheimer's disease cells abnormal abnormally accumulate beta-amyloid harbouring peptides preferentially in cytosol but not in extracelluar fluid Matsmoto A;Matsumoto R
  26. Neuroreport v.8 Block of late-phase long-term potentiation in rat hippocampus in vivo by amyloid precursor protein fragments Cullen WK;Suh YH;Anwyl R;Rowan MJ
  27. Nat Med. v.6 no.4 A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor Lu DC;Rabizadeh S;Chandra S;Shayya RF;Ellerby LM;Ye X(et al.)
  28. Biol Psychiatry v.49 no.3 Effects of nicotine on APP secretion and Abeta- or CT(105)-induced toxicity Seo J;Kim S;Kim H;Park CH;Jeong S;Lee J;Choi SH;Chang K;Rah J;Koo J;Kim E; Suh
  29. J. Neural Transm v.58 no.Suppl. Roles of A beta and carboxyl terminal peptide fragments of amyloid precursor protein in Alzheimer disease Suh YH;Kim HS;Lee JP;Park CH;Jeong SJ;Kim SS;Rah JC;Seo JH;Kim S
  30. 景岳全書 張景岳
  31. 동의신경정신과학회지 v.7 no.1 치매에 대한 문헌적 고찰 정인철;이상용
  32. 中醫雜誌 v.38 no.10 謝海洲治療腦萎縮經驗 郭字鵬(外)
  33. 本草學 강병수(외)
  34. 本草集成 서부일;김상찬(監修)
  35. 東醫神經精神科學會誌 v.10 no.1 遠志에 의한 腦 星狀細胞로부터 炎症性 細胞活性物質 分泌의 抑制 效果에 關한 硏究 황시영;강형원;유영수
  36. 동의생리병리학회지 v.16 no.2 山査肉이 Alzheimer's disease 병태 모델에 미치는 영향 정인철;이상룡
  37. 大韓韓醫學會誌 v.17 no.1 左歸飮과 右歸飮에 의한 活性 酸素類의 消去작용과 抗酸化 酸素系의 活性 增加 효과에 대한 硏究 鄭智天
  38. 동의신경정신과학회지 v.12 no.2 생체외 알츠하이머병 실험모델에서 星香正氣散加蒲公英의 효과에 관한 연구 박진성;강형원;유영수
  39. 동의병리학회지 v.13 no.1 치매의 병리에 대한 동서의학적 고찰 강형원(외)