본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Inhibition of Angiotensin II-Induced Vascular Smooth Muscle Cell Hypertrophy by Different Catechins

Zheng, Ying    (Department of Pharmacology, College of Medicine, Chungbuk National University   ); Song, Hye-Jin    (Department of Pharmacology, College of Medicine, Chungbuk National University   ); Yun, Seok-Hee    (Department of Pharmacology, College of Medicine, Chungbuk National University   ); Chae, Yeon-Jeong    (Department of Pharmacology, College of Medicine, Chungbuk National University   ); Jia, Hao    (Department of Pharmacology, College of Medicine, Chungbuk National University   ); Kim, Chan-Hyung    (Department of Pharmacology, College of Medicine, Chungbuk National University   ); Ha, Tae-Sun    (Department of Pediatrics, College of Medicine, Chungbuk National University   ); Sachinidis, Agapios    (Center of Physiology and Pathophysiology, University of Cologne   ); Ahn, Hee-Yul    (Department of Pharmacology, College of Medicine, Chungbuk National University   ); Davidge, Sandra T.    (Department of Obstetrics and Gynecology and Physiology, Perinatal Research Center, University of Alberta  );
  • 초록

    A cumulative evidence indicates that consumption of tea catechin, flavan-3-ol derived from green tea leaves, lowers the risk of cardiovascular diseases. However, a precise mechanism for this cardiovascular action has not yet been fully understood. In the present study, we investigated the effects of different green tea catechins, such as epigallocatechin-3 gallate (EGCG), epigallocatechin (EGC), epicatechin-3 gallate (ECG), and epicatechin (EC), on angiotensin II (Ang II)-induced hypertrophy in primary cultured rat aortic vascular smooth muscle cell (VSMC). [ $^3H$ ]-leucine incorporation was used to assess VSMC hypertrophy, protein kinase assay, and western blot analysis were used to assess mitogen-activated protein kinase (MAPK) activity, and RT-PCR was used to assess c-jun or c-fos transcription. Ang II increased [ $^3H$ ]-leucine incorporation into VSMC. However, EGCG and ECG, but not EGC or EC, inhibited [ $^3H$ ]-leucine incorporation increased by Ang II. Ang II increased phosphorylation of c-Jun, extracellular-signal regulated kinase (ERK) 1/2 and p38 MAPK in VSMC, however, EGCG and ECG , but not EGC or EC, attenuated c-Jun phosphorylation increased by Ang II. ERK 1/2 and p38 MAPK phosphorylation induced by Ang II were not affected by any catechins. Ang II increased c-jun and c-fos mRNA expression in VSMC, however, EGCG inhibited c-jun but not c-fos mRNA expression induced by Ang II. ECG, EGC and EC did not affect c-jun or c-fos mRNA expression induced by Ang II. Our findings indicate that the galloyl group in the position 3 of the catechin structure of EGCG or ECG is essential for inhibiting VSMC hypertrophy induced by Ang II via the specific inhibition of JNK signaling pathway, which may explain the beneficial effects of green tea catechin on the pathogenesis of cardiovascular diseases observed in several epidemiological studies.


  • 주제어

    Angiotensin II .   VSMC .   Hypertrophy .   Catechin .   JNK.  

  • 참고문헌 (41)

    1. Kallunki T, Deng T, Hibi M, Karin M. c-Jun can recruit JNK to phosphorylate dimerization partners via specific docking interactions. Cell 87: 929-939, 1996 
    2. Nagai K, Jiang MH, Hada J, Nagata T, Yajima Y, Yamamoto S, Nishizaki T. (-)-Epigallocatechin gallate protects against NO stress-induced neuronal damage after ischemia by acting as an anti-oxidant. Brain Res 956: 319-322, 2002 
    3. Owens GK, Schwartz SM. Vascular smooth muscle cell hypertrophy and hyperploidy in the Goldblatt hypertensive rat. Circ Res 53: 491-501, 1983 
    4. Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR. Phosphorylation of c-jun mediated by MAP kinases. Nature 353: 67-674, 1991 
    5. Salah N, Miller NJ, Paganga G, Tijburg L, Bolwell GP, Rice-Evans C. Polyphenolic flavonols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys 322: 339-346, 1995 
    6. Servant MJ, Giasson E, Meloche S. Inhibition of growth factorinduced protein synthesis by a selective MEK inhibitor in aortic smooth muscle cells. J Biol Chem 271: 16047-16052, 1996 
    7. Ushio-Fukai M, Alexander RW, Akers M, Griendling KK. p38 mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin II. Role in vascular smooth muscle cell hypertrophy. J Biol Chem 273: 15022-15029, 1998 
    8. Ushio-Fukai M, Alexander RW, Akers M, Yin Q, Fujio Y, Walsh K, Griendling KK. Reactive oxygen species mediate the activation of Akt/protein kinase by angiotensin II in vascular smooth muscle cells. J Bio Che 274: 22699-22704, 1999 
    9. Geisterfer AA, Peach MJ, Owens GK. Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 62: 749-756, 1988 
    10. Middleton Jr E, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacol Rev 52: 673-751, 2000 
    11. Karin M. The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270: 16483-16486, 1995 
    12. Rivera VM, Greenberg ME. Growth factor-induced gene expression: the ups and downs of c-fos regulation. New Biol 2: 751-758, 1990 
    13. Yoshizumi M, Tsuchiya K, Suzaki Y, Kirima K, Kyaw M, Moon JH, Terao J, Tamaki T. Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway. Biochem Biophys Res Commun 293: 1458-1465, 2002 
    14. Zheng Y, Song HJ, Kim CH, Kim HS, Kim EG, Sachinidis A, Ahn HY. Inhibitory effect of epigallocatechin 3-O-gallate on vascular smooth muscle cell hypertrophy induced by angiotensin II. J Cardiovasc Pharmacol 43: 200-208, 2004 
    15. Benelli R, Vene R, Bisacchi D, Garbisa S, Albini A. Anti-invasive effects of green tea polyphenol epigallocatechin-3-gallate (EGCG), a natural inhibitor of metallo and serine proteases. Biol Chem 383: 101-105, 2002 
    16. Giasson E, Meloche S. Role of P70 S6 protein kinase in angiotensin II-induced protein synthesis in vascular smooth muscle cells. J Biol Chem 270: 5225-5231, 1995 
    17. Kang WS, Chung KH, Chung JH, Lee JY, Park JB, Zhang YH, Yoo HS, Yun YP. Antiplatelet activity of green tea catechins is mediated by inhibition of cytoplasmic calcium increase. J Cardiovascular Pharmacol 38: 875-884, 2001 
    18. McKay S, de Jongste JC, Saxena PR, Sharma HS. Angiotensin II induces hypertrophy of human airway smooth muscle cells: expression of transcription factors and transforming growth factor-beta1. Am J Respir Cell Mol Biol 18: 823-833, 1998 
    19. Smeal T, Hibi M, Kanin M. Altering the specificity of signal transduction cascades:positive regulation of c-Jun transcriptional activity by protein kinase A. EMBO 3: 6006-6010, 1994 
    20. Hixon ML, Muro-Cacho C, Wagner MW, Obejero-Paz C, Mille E, Fujio Y, Kureishi Y, Hassold T. Walsh K, Gualberto A. Akt/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization. J Clin Invest 106: 1011-1020, 2000 
    21. Eguchi S, Iwasaki H, Ueno H, Frank GD, Motley ED, Eguchi K, Marumo F, Hirata Y, Inagami T. Intracellular signaling of angiotensin II-induced P70 S6 kinase phosphorylation at Ser411 in vascular smooth muscle cells. Possible requirement of epidermal growth factor receptor, Ras, extracellular signal-regulated kinase and Akt. J Biol Chem 274: 36843-36851, 1999 
    22. Musti AM, Treier M, Bohmann D. Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases. Science 275: 400-402, 1997 
    23. Yamane T, Takahashi T, Kuwata K, Oya K, Inagake M, Kitao Y, Suganuma M, Fujiki H. Inhibition of N-methyl-N'-nitro-N-nitrosoguanidine-induced carcinogenesis by (-)-epigallocatechin gallate in the rat glandular stomach. Cancer Res 55: 2081-2084, 1995 
    24. Berk BC, Corson MA. Angiotensin II signal transduction in vascular smooth muscle. Circ Res 80: 607-616, 1997 
    25. Gille H, Sharrocks A, Shaw P. Phosphorylation of p62TCF by MAP kinases stimulates ternary complex formation at c-Fos promoter. Nature 358: 414-417, 1992 
    26. Sachinids A, Skach RA, Seul C, Ko Y, Hescheler J, Ahn HY, Fingerle J. Inhibition of the PDGF -receptor tyrosine phosohorylation and its downstream intracellular signal transduction pathway in rat and human vascular smooth muscle cells by different catechins. FASEB J 16: 893-895, 2002 
    27. Berk BC, Vekshtein V, Gordon HM, Tsuda T. Angiotensin IIstimulated protein synthesis in cultured smooth muscle cells. Hypertension 13: 305-314, 1989 
    28. Weber AA, Neuhaus T, Skach RA, Hescheler J, Ahn HY, Schror K, Ko Y, Sachinidis A. Mechanisms of the inhibitory effects of epigallocatechin-3 gallate on platelet-derived growth factor-BBinduced cell signaling and mitogenesis. FASEB J 18: 128-130, 2004 
    29. Yamaguchi K, Honda M, Ikigai H, Hara Y, Shimamura T. Inhibitory effects of (-)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type I (HIV-1). Antiviral Res 53: 19-34, 2002 
    30. Ahn HY, Hadizadeh KR, Seul C, Yun YP, Vetter H, Sachinidis A. Epigallocatechin-3 gallate selectively inhibits the PDGF-BB-induced intracellular signaling transduction pathway in vascular smooth muscle cells and inhibits transformation of sis-transfected NIH 3T3 fibroblasts and human glioblastoma cells (A172). Mol Biol Cell 10: 1093-1104, 1999 
    31. Owens GK, Schwartz SM. Alterations in vascular smooth muscle mass in the spontaneously hypertensive rat. Role of cellular hypertrophy, hyperploidy, and hyperplasia. Circ Res 51: 280-289, 1982 
    32. Tijburg LB, Mattern T, Folts JD, Weisgerber UM, Katan MB. Tea flavonoids and cardiovascular diseases. Crit Rev Food Sci 37: 771-785, 1997 
    33. Imai K, Nakachi K. Cross sectional study of effects of drinking green tea on cardiovascular and liver diseases. Br Med J 310: 693-696, 1995 
    34. Nakagawa T, Yokozawa T. Direct scavenging of nitric oxide and superoxide by green tea. Food Chem Toxicol 40: 1745-1750, 2002 
    35. Santana-Rios G, Orner GA, Amantana A, Provost C, Wu SY, Dashwood RH. Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay. Mutat Res 495: 61-74, 2001 
    36. Takahashi T, Kawahara Y, Okuda M, Ueno H, Takeshita A, Yokoyama M. Angiotensin II stimulates mitogen-activated protein kinases and protein synthesis by a Ras-independent pathway in vascular smooth muscle cells. J Biol Chem 272: 16018-16022, 1997 
    37. Takahashi T, Taniguchi T, Konishi H, Kikkawa U, Ishikawa Y, Yokoyama M. Activation of Akt/protein kinase B after stimulation with angiotensin II in vascular smooth muscle cell. Am J Physiol 276: H1927-H1934, 1999 
    38. Yoshizumi M, Tsuchiya K, Kirima K, Kyaw M, Suzaki Y, Tamaki T. Quercetin inhibits Shc- and phosphatidylinositol 3-kinasemediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells. Mol Pharmacol 60: 656-665, 2001 
    39. Black MJ, Adams MA, Bobik A, Campbell JH, Campbell GR. Vascular smooth muscle polyploidy in the development and regression of hypertension. Clin Exp Pharmacol Physiol 15: 345-348, 1988 
    40. Hwang KC, Lee KH, Jang Y, Yun YP, Chung KH. Epigallocatechin-3-gallate inhibits basic fibroblast growth factor- induced intracellular signaling transduction pathway in rat aortic smooth muscle cells. J Cardiovasc Pharmacol 39: 271-277, 2002 
    41. Takeuchi K, Nakamura N, Cook NS, Pratt RE, Dzau VJ. Angiotensin II can regulate gene expression by the AP-1 binding sequence via a protein kinase C-dependent pathway. Biochem Biophys Res Commun 172: 1189-1194, 1990 
  • 이 논문을 인용한 문헌 (2)

    1. 2009. "" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 13(5): 385~392     
    2. 2010. "" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 14(5): 325~329     

 저자의 다른 논문

  • 하태선 (29)

    1. 2000 "Henoch-$Sch\ddot{o}nlein$ 자반증 환아에서 신침범에 대한 위험인자 분석 및 tumor necrosis factor-$\alpha$의 의의" 대한소아신장학회지 = Journal of the Korean society of pediatric nephrology 4 (1): 40~47    
    2. 2001 "IgA Nephropathy와 Henoch-$Sch{\ddot{o}}nlein$ Purpura가 동일 병인임을 시사하는 2례" 대한소아신장학회지 = Journal of the Korean society of pediatric nephrology 5 (1): 59~63    
    3. 2002 "Henoch-Schönlein Purpura 신염과 특발성 신증후군에서 Tumor Necrosis Factor Alpha와 단백뇨와의 관련성에 관한 임상적 연구" 소아과 = Journal of the Korean pediatric society 45 (2): 240~246    
    4. 2003 "급성 신우신염 환아들의 나이에 따른 Dimercaptosuccinic Acid Renal Scan 민감도" 대한소아신장학회지 = Journal of the Korean society of pediatric nephrology 7 (1): 38~43    
    5. 2003 "아메바성 장염과 관련된 용혈성 요독 증후군" 대한소아신장학회지 = Journal of the Korean society of pediatric nephrology 7 (1): 82~85    
    6. 2003 "Henoch-Schönlein 자반증 환아의 임상적 고찰" 소아과 = Journal of the Korean pediatric society 46 (11): 1118~1123    
    7. 2004 "당과 후기당화합물에 의한 사구체 상피세포 ZO-1 발현의 변화" 대한소아신장학회지 = Journal of the Korean society of pediatric nephrology 8 (2): 138~148    
    8. 2004 "심낭삼출로 발병하여 스테로이드 단독치료로 호전된 소아 전신성 홍반성 낭창 1례" 대한소아신장학회지 = Journal of the Korean society of pediatric nephrology 8 (1): 80~85    
    9. 2005 "배양한 사구체 상피세포에서 고농도 당과 후기 당화합물에 의한 P-cadherin의 변화" 대한소아신장학회지 = Journal of the Korean society of pediatric nephrology 9 (2): 119~127    
    10. 2005 "전신적 경련 후 발생한 횡문근융해증에 의해 초래된 급성신부전 1례" 대한소아신장학회지 = Journal of the Korean society of pediatric nephrology 9 (2): 251~254    
  • Ahn, Hee Yul (13)

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • NDSL :
  • 대한약리학회 : 저널
  • 대한생리학회 : 저널
유료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기