동의신경정신과학회지 (Journal of Oriental Neuropsychiatry)

  • 제20권1호
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  • Pages.147-164
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  • 2009
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  • 1226-6396(pISSN)
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  • 2234-4942(eISSN)
대한한방신경정신과학회 (The Korean Society of Oriental Neuropsychiatry)
권호 표지

소풍순기원(疏風順氣元)이 mouse의 NMu2Li 간세포와 C2C12 골격근세포에서 PPARs 조절의 분자기전에 미치는 영향

A Molecular Study of Sopungsungi-won(Shufengshunqiyuan) about Regulation of PPARs in Mouse NMu2Li Liver Cells and C2C12 Skeletal Muscle Myogenic Progenital Cells

  • 오영진 (동의대학교 한의과대학 한방신경정신과학 교실) ;
  • 신순식 (동의대학교 한의과대학 방제학교실) ;
  • 윤미정 (목원대학교 바이오건강학부) ;
  • 김보경 (동의대학교 한의과대학 한방신경정신과학 교실)
  • Oh, Young-Jin (Dept. of Formula Sciences College of Oriental Medicine, Dongeui University) ;
  • Shin, Soon-Shik (Dept. of Neuropsychiatry College of Oriental Medicine, Dongeui University) ;
  • Yoon, Mi-Chung (Department of Life Sciences, Mokwon University) ;
  • Kim, Bo-Kyung (Dept. of Formula Sciences College of Oriental Medicine, Dongeui University)
  • 발행 : 2009.03.30
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초록

Objectives : We investigated the effects of Sopungsungi-won(Shu!engshunqiyuan) (SSEx1, SSEx2) to treat the metabolic syndrome by the molecular mechanism of regulation of PPAR and modulation of mitochondrial MCAD, VLCAD mRNA expression. Methods : Mouse NMu2Li liver cells and C2C12 skeletal muscle myogenic progenital cells were transiently transfected with expression plasmids for PPAR(PPAR${\alpha}$, PPAR${\delta}$), a luciferase reporter gene construct containing 3 copies of the PPRE from the rat acyl-CoA oxidase gene and ${\beta}$-galactosidase gene. Cells were treated with several concentrated kinds of SSEx1, SSEx2 at the initial time of culture and analyzed PPAR${\alpha}$, PPAR${\delta}$ reporter gene activity using spectrophotometer (405 nm). Total RNA was extracted from SSEx1, SSEx2 and measured mRNA levels of mitochondrial MCAD, VLCAD. Representative RT-PCR bands are shown. Results : 1. SSEx1 increased the expression of PPAR${\alpha}$ reporter gene activities at 0.1 ${\mu}$g/ml (p${\mu}$g/ml (p<0.05), SSEx2 at 0.1 ${\mu}$g/ml (p${\mu}$g/ml (p<0.05) significantly in NMu2Li liver cell lines. 2. SSEx1 increased the expression of PPAR${\alpha}$ reporter gene activities at 1 ${\mu}$g/ml (p${\mu}$g/ml (p${\alpha}$ reporter gene activities in C2C12 skeletal muscle cells. 4. SSEx1 increased the modulation of mitochondrial MCAD mRNA expression (p<0.05) significantly in NMu2Li liver cell lines. 5. SSEx1, SSEx2 both increased the modulation of mitochondrial MCAD mRNA expression (p<0.05) significantly in C2C12 skeletal muscle cells. Conclusions : These results show the SSEx1, SSEx2 can be used as therapeutic agent for metabolic syndrome and it's molecular mechanisms of PPAR more contribute to the activation of PPAR${\alpha}$ then PPAR${\delta}$ reporter gene activities and it's total RNA more contribute to the modulation of mitochondrial MCAD then VLCAD mRNA expression.

키워드

참고문헌

  1. Reaven GM. Role of insulin resistance in human disease. Diabetes. 1999;37:1595-607. https://doi.org/10.2337/diabetes.37.12.1595
  2. Journal of the American Medical Association(JAMA). National Cholesterol Education Program:Executive summary of the third report of the national cholesterol education program(NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults(adult treatment panel III). Circulation. 2001;285:2488-97.
  3. 임수, 이은정, 구보경, 조성일, 박경수, 장학철, 김성연, 이홍규. 국민건강영양조사에 근거한 한국인의 대사증후군의 증가양상. 당뇨병학회지. 2005;19(5):432-9.
  4. 권혁상. 대사증후군의 역학 및 병인. 대한당뇨병학회지. 2006;7(1):12-9.
  5. Kliewer SA, Lehmann JM, Willson TM. Orphan nuclear receptors:shifting endocrinology into reverse. Science. 1999;284:757-60. https://doi.org/10.1126/science.284.5415.757
  6. Gustafsson JA. Seeking ligands for lonely orphan receptors. Science. 1999;284:1285-6. https://doi.org/10.1126/science.284.5418.1285
  7. 이기업. 대사증후군의 치료. 한국지질동맥경화학회지. 2002;12(1):31-5.
  8. 양유걸. 황제내경소문역해. 서울:성보사. 1980:19.
  9. 진월인. 난경입문. 서울:법인문화사. 1998:338-40.
  10. 전국한의과대학 신경정신과 교과서편찬위원회. 한의신경정신과학. 서울:집문당. 2007:630-1.
  11. 武市昌士. 미병의 동서의학. 서울:군자출판사. 2008:23-5.
  12. 危亦林. 世醫得效方. 北京:中國中醫藥出版社. 1996:98.
  13. 허준. 동의보감. 서울:법인문화사. 1999:140,470,945,948,962,964.
  14. 전국한의과대학 본초학교수 공편저. 본초학. 서울:영림사. 1999:131,242,246,247, 260,313,351,378,427,537,568,626.
  15. 任汉陽, 等. 火麻仁油的降脂及對過氧化脂質 作用的實驗硏究. 中國中醫藥科技. 1997;4(4):200.
  16. Luthra YK, Rosenkrantz H, Braude MC. Cerebral and cerebellar neurochemical changes and behavioral manifestations in rats chronically exposed to marijuana smoke. Toxicology and Applied Pharmacology. 1976;35(3):455-65. https://doi.org/10.1016/0041-008X(76)90068-5
  17. Barnett G, Chiang CW, Perez-Reyes M, Owens SM. Kinetic study of smoking marijuana. J. Pharmacokinetics and Biopharmaceutics. 1982;10(5):495-506. https://doi.org/10.1007/BF01059033
  18. Mason AP, McBay AJ. Cannabis:pharmacology and interpretation of effects. J. Forensics Sciences. 1985;30(3):615-31.
  19. 정재욱. 중풍환자의 변비에 대한 소풍순기원의 임상적 연구. 동의대학교 석사학위논문. 2005.
  20. 이성현, 안세영, 두호경, 정성현. db/db 마우스에서 수풍순기환의 혈당강하 및 기전연구. 응용약물학회지. 1999;7:335-41.
  21. 배미라, 정성현. 고지방식이 섭취 마우스에서 수풍순기환의 혈당강하활성 및 기전. 경희약대논문집. 2000;28:101-8.
  22. McAinch AJ, Lee JS, Burce CR, Tunstall RJ, Hawley JA, Cameron-Smith D. Dietary regulation of fat oxidative gene expression in different skeletal muscle fiber types. Obesity Res. 2003;11(12):1471-9. https://doi.org/10.1038/oby.2003.197
  23. Van Der Lee KA, Willemsen PH, Van Der Vusse GJ, Van Bilsen M. Effect of fatty acids on uncoupling protein 2 expression in the rat heart. FASEB J. 2000;14(3):495-502.
  24. Wu P, Peters JM, Harris RA. Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is medicated by peroxisome proliferators-activated receptor alpha. Biochem Biophys Res Commun. 2001;287(2):391-6. https://doi.org/10.1006/bbrc.2001.5608
  25. Young ME, Goodwin GW, Ying J, Guthrie P, Wilson CR, Laws FA, Taegtmeyer H. Regulation of cardiac and skeletal muscle malonyl CaA decarboxylase by fatty acids. Am J Physiol Endocrinol Metab. 2001;280(3):471-9.
  26. Lake BG. Mechanisms of hepatocarcinogenicity of peroxisome-proliferating drugs and chemicals. Annu Rev Pharmacol Toxicol. 1995;35:483-507. https://doi.org/10.1146/annurev.pa.35.040195.002411
  27. Glass BG. Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr Rev. 1994;15(3):391-407.
  28. Claudel T, Leibowitz MD, Fiévet C, Tailleux A, Wagner B, Repa JJ, Torpier G, Lo. Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor. Proc Natl Acad Sci U S A. 2001;98(5):2610-5. https://doi.org/10.1073/pnas.041609298
  29. Schoonjan K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res. 1996;37(5):907-25.
  30. Neve BP, Fruchart J-C, Staels B. Role of the peroxisome proliferator-activated receptors (PPARs) in atherosclerosis. Biochem Pharmacol. 2000;60(8):1245-50. https://doi.org/10.1016/S0006-2952(00)00430-5
  31. Chaput E, Saladin R, Silvestre M, Edgar AD. Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun. 2000;271(2):445-50. https://doi.org/10.1006/bbrc.2000.2647
  32. Guerre-Millo M, Gervois D, Raspe E, Madsen L, Poulain P, Derudas B, Herbert JM. Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000;275(22):16638-42. https://doi.org/10.1074/jbc.275.22.16638
  33. Mancini FP, Lanni A, Sabatino L, Moreno M, Giannino A, Contaldo F, Colantuoni C. Fenofibrate prevents and reduces body weight gain and adiposity in diet-induced obese rats. FEBS Lett. 2001;491(1/2):154-8. https://doi.org/10.1016/S0014-5793(01)02146-9
  34. Grimaldi PA. The roles of PPARs in adipocyte differentiation. Prog Lipid Res. 2001;40(4):269-81. https://doi.org/10.1016/S0163-7827(01)00005-4
  35. Lim H, Gupta RA, Ma WG, Paria BC, Moller DE, Morrow JD, DuBois RN, Trzaskos JM. Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Genes Dev. 1999;13(12):1561-74. https://doi.org/10.1101/gad.13.12.1561
  36. Soon TN, Liliane M, Beatrice D, Walter W. Peroxisome proliferator-activated receptor (PPAR)-beta as a target for wound healing drugs: what is possible? Am J Clin Dermatol. 2003;4(8):523-30. https://doi.org/10.2165/00128071-200304080-00001
  37. Poirier H, Niot I, Monnot MC, Braissant O, Meunier-Durmort C, Costet P, Pineau T, Wah. Differential involvement of peroxisome-proliferator-activated receptors alpha and delta in fibrate and fatty-acid-mediated inductions of the gene encoding liver fatty-acid-binding protein in the liver and the small intestine. Biochem J. 2001;355(Pt 2):481-8. https://doi.org/10.1042/0264-6021:3550481
  38. Peters JM, Lee SS, Ward JM, Gavrilova O, Everett C, Reitman ML, Hudson LD. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol. 2000;20(14):5119-28. https://doi.org/10.1128/MCB.20.14.5119-5128.2000
  39. Tanaka T, Yamamoto J, Iwasaki S, Asaba H, Hamura H, Ikeda Y. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome. Proc Natl Acad Sci U S A. 2003;100(26):15924-9. https://doi.org/10.1073/pnas.0306981100
  40. Wang YX, Lee CH, Tiep SB, Yu RT, Ham JY, Kang HJ, Evans. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell. 2003;113(2):159-70. https://doi.org/10.1016/S0092-8674(03)00269-1
  41. Muoio DM, MacLean PS, Lang DB, Lis, Houmard JA, Way JM, Winegar DA. Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) alpha knock-out mice. Evidence for compensatory regulation by PPAR delta. J Biol Chem. 2002;277(29):26089-97. https://doi.org/10.1074/jbc.M203997200
  42. Dorte H, Serge L, Véronique N, Karsten K, Xavier L, G. Nutritional regulation and role of peroxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle. Biochim Biophys Acta. 2003;1633(1):43-50. https://doi.org/10.1016/S1388-1981(03)00071-4
  43. Braissant O, Foufelle F, Scotto C, Dauça M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs):tissue distribution of PPAR-alpha, -beta, -gamma in the adult rat. Endocrinology. 1996;137(1):354-66. https://doi.org/10.1210/en.137.1.354
  44. Rangwala, Shamina M, Lazar, Mitchell A. Peroxisome proliferator-activated receptor gamma in diabetes and metabolism. Trends Pharmacol Sci. 2004;25(6):331-6. https://doi.org/10.1016/j.tips.2004.03.012
  45. 고대희. 대마(Cannabis sativa L.)씨의 지방산 조성에 관한 연구. 한국식품영양학회지. 1990;3(2):201-6.