Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
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Changes in the Expression Pattern of Cyclooxygenase-2, Mapkinases and Related Apoptotic Markers by Different Levels of Estrogen Supplementation in Mature or Ovariectomized Female Rat Heart

에스트로겐에 의한 암쥐의 심장조직의 COX-2, Mapkinases 및 관련된 Apoptotic Markers의 발현의 변화에 관한 연구

  • 신장인 (한남대학교 식품영양학과) ;
  • 박옥진 (한남대학교 식품영양학과)
  • Published : 2005.01.01
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Abstract

The effects of different concentrations of estrogen supplementation to mature female rats or estrogen supplementation to ovariectomized rats on cyclooxygenase-2 (COX-2) expression, PGE$_2$ production and mapkinases expression were investigated in experimentally induced atherogenic rats with feeding a high fat. high cholesterol diet. In the first experiment using 48-week old mature rats, the supplementation of three different levels of estrogen was compared to the basal diet. The high concentration of estrogen supplementation induced the marked up-regulation of COX-2 protein and the increase in plasma PGE$_2$ production and this seems to be followed by the up-regulation of p38 among mapkinases. The regulation of bax showed in a reverse trend of COX-2 in heart tissues of mature female rats. In the second ex-perimental system, female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were supplied with basal diet to sham-operated control group and ovariectomized control group, and estrogen supplemented diet to ovariectomized group for an eight-week experimental period. In a group supplemented with a medium dose of estrogen, COX-2 expression was up-regulated. This up-regulation was accompanied by the elevated expression of pERK1/2. Bax was increased in estrogen-fed animals indicating bax might be involved in estrogen feeding state in ovariectomized rats. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by estrogen are required in in vivo system of female rats at the various physiological states.

Keywords

References

  1. Barrett-Connor E, Bush TL, Estrogen and the coronary heart disease in women. J Am Med Assoc 265: 1861-1867, 1991 https://doi.org/10.1001/jama.265.14.1861
  2. Knopp RH, Zhu X, Bonet B. Effects of estrogens in lipoprotein metabolism and cardiovascular disease in women. Atherosclerosis 110: S83-S91, 1994 https://doi.org/10.1016/0021-9150(94)05379-W
  3. Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med 20: 47-63, 1991 https://doi.org/10.1016/0091-7435(91)90006-P
  4. Mikkola TS, Clarkson TB. Estrogen replacement therapy, atherosclerosis and vascular function. Cardiovasc Res 53: 605-619, 2002 https://doi.org/10.1016/S0008-6363(01)00466-7
  5. Knopp RH, Zuh X, Bonet B. Effects of estrogens in lipoprotein metabolism and cardiovascular disease in women. Atherosclerosis 110: S83-S91, 1994 https://doi.org/10.1016/0021-9150(94)05379-W
  6. Koh KK. Vascular effects of estrogen and vitamin E therapies in postmenopausal women. Circulation 100: 717-722, 1999
  7. Squadrito F, Altavilla D, Squadrito G, Saitta A, Cucinotta D, Minutuli L, Deodato B, Ferlito M, Campo GM, Bova A, Caputi AP. Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats. Cadiovas Res 45: 454-462, 2000 https://doi.org/10.1016/S0008-6363(99)00359-4
  8. Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and risk of cardiovascular disease: the Framingham study. Ann Intern Med 85: 447-452, 1976
  9. Egan KM, Lawson JA, Fries S, Koller B, Rader DJ, Smyth EM, Fitzgerald GA. COX-2 derived prostacyclin confers atheroprotection on female mice. Science 306: 1954-1957, 2004 https://doi.org/10.1126/science.1103333
  10. Hla T, Neilson K. Human cycooxygenase-2 cDNA. Pro Natl Acad Sci USA 89: 7384-7388, 1992
  11. Caughey GE, Cleland LG, Penglis PS, Gamble JR, Janes MJ. Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid producion by human endothelial cells: selective up-regulation of prostacyclin synthesis by COX-2. J Immunol 167: 28231-28238, 2001
  12. Ghanam K, Lavagna C, Burgaud J-L, Javellaud J, Ea-Kim L, Oudart N. Involvement of cyclooxygenase 2 in the protective effect of 17 ${\beta}$-estradiol in hypercholesterolemic rabbit aorta. Biochem Biophy Resear Comm 275: 696-703, 2000 https://doi.org/10.1006/bbrc.2000.3278
  13. Hyslop S, De Nucci G. Prostaglandin biosynthesis in the microcirculation: regulation by endothelial and non-endothelial factors. Leukotrienes Essent Fatty Acids 49: 723-760, 1993 https://doi.org/10.1016/0952-3278(93)90021-N
  14. Ge T, Hughes H, Junquero DC, Wu KK, Vanhoutte PM, Boulanger CM. Endothelium-dependent contractions are associated with both augmented expression of prostaglandin H synthase-1 and hypersensitivity to prostaglandin $H_{2}$ in the SHR aorta. Cir Res 76: 1003-1010, 1995
  15. Dyer SM, Taylor DA, Bexis S, Hime NJ, Frewin DB, Head RJ. Identification of a non-endothelial cell thromboxane-like constrictor response and its interaction with the renin-angiotensin system in the aorta of spontaneously hypertensive rats. J Vase Res 31: 5-60, 1994
  16. Wong E, Huang J, Tagari P, Riendear D. Effects of COX-2 inhibitors on aortic prostacyclin production in cholesterol-fed rabbits. Atherosclerosis 157: 393-402, 2001 https://doi.org/10.1016/S0021-9150(00)00756-5
  17. Smith WL. Prostaglandin synthesis and its compartmentation in vascular muscle and endothelial cells. Ann Rev Physiol 48: 251-262, 1986 https://doi.org/10.1146/annurev.ph.48.030186.001343
  18. Bishop-Bailey D, Pepper JR, Larkin SW, Mitchell JA. Differential induction of cyclooxygenase-2 in human arterial and venous smooth muscle. Role of endogenous prostanoids. Arterioscler Thromb Vase Biol 18: 1655-1661, 1998
  19. Asano H, Shimizu K, Muramatsu M, Iwama Y, Toki Y, Miyazaki Y, Okumura K, Hashimoto H, Ito T. Prostaglandin H2 as an endothelium-derived contracting factor modulates endothelin-linduced contraction. J Hyperten 12: 383-390, 1994
  20. Dyer SM, Taylor DA, Bexis S, Hime NJ, Frewin DB, Head RJ. Identification of a non-endothelial cell thromboxane-like constrictor response and its interaction with the renin-angiotensin system in the aorta of spontaneously hypertensive rats. J Vase Res 31: 5-60, 1994
  21. Ross R. Atherosclerosis: an inflammatory disease. N Eng J Med 340: 115-126, 1999 https://doi.org/10.1056/NEJM199901143400207
  22. Schonbeck U, Sukhova GK, Graber P. Augmented expression of cyclooxygenase-2 in human atherosclerotic lesions. Am J Physiol 155: 1281-1291, 1999
  23. Burleigh ME, Babev VR, Oates JA, Harris RC, Gautam S, Riendeau D, Marnett D, Morrow JD, Fazio S, Linton ME Cyclooxygenase-2 promotes early atherosclerotic lesion formation in LDL receptor-deficient mice. Circulation 105: 1816-1823, 2002 https://doi.org/10.1161/01.CIR.0000014927.74465.7F
  24. Grodstein F. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 335: 453-461, 1996 https://doi.org/10.1056/NEJM199608153350701
  25. Hodis HN, et al. Estrogen in the prevention of atherosclerosis. A randomized, double-blind placebo-controlled trial. Arch Inter Med 135: 939-953, 2001
  26. Grodstein F, et al. Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med 348: 645-650, 2003 https://doi.org/10.1056/NEJMsb022365
  27. Hully S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff. Randomized trial of estrogen plus progestin for secondary prevention on coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) research Group. J Am Med Assoc 280: 605-613, 1998 https://doi.org/10.1001/jama.280.7.605
  28. Rossouw JE, Anderson GL, Prentice RL, LaCorix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. J Am Med Assoc 288: 321-333, 2002 https://doi.org/10.1001/jama.288.3.321
  29. Cid MC, et al. Estradiol enhances leukocyte binding to tumor necrosis fator (TNF)-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type 1, and vascular cell adhesion moelcule type 1. J Clin Invest 93: 17-25, 1994 https://doi.org/10.1172/JCI116941
  30. Rossig L, Kimmeler S, Zeiher AM. Apoptosis in the vascular wall and atherosclerosis. Basic Res Cardiol 96: 11-22, 2001 https://doi.org/10.1007/s003950170073
  31. Lusis AJ. Atherosclerosis. Nature 407: 233-241, 2000 https://doi.org/10.1038/35025203
  32. Liu J, Thewke DP, Su YR, Linton MF, Fazio S, Sinensky MS. Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice. Arter Thrmob Base Biol Oct 21, 2004
  33. Jesmin S, Sakuma I, Hattori Y, Kitabatake A. In vivo estrogen manipulations on coronary capillary network and angiogenic molecule expression in middle-aged female rats. Arter Thromb Vase Biol 22: 1591-1597, 2002 https://doi.org/10.1161/01.ATV.0000034929.42459.0D
  34. Watanabe T, Miyahara Y, Masahiro A, Nakaoka T, Yamashita N, Iijima K, Kim H, Kozaki K and Ouch Y. Inhibitory effect of low-dose estrogen neointimal formation after balloon injury of rat carotid artery. Eur J Pharamcol 502: 265-270, 2004 https://doi.org/10.1016/j.ejphar.2004.09.011
  35. Nilsson S. Mechanisms of estrogen action. Physiol Rev 81: 1535-1565, 2001
  36. Stork S, Schouw YT, Grobbee DE, Bots ML. Estrogen, inflammation and cardiovascular risk in women: a critical appraisal. Trends Endocrinol Metabolism 15: 66-72, 2004 https://doi.org/10.1016/j.tem.2004.01.005
  37. Karas RH, Clarkson TB. Considerations in interpreting the cardiovascular effects of hormone replacement therapy observed in the WHI: timing is everything. Menopausal Med 10: 8-11, 2003
  38. Huang A, Kaley G. Gender-specific regulation of cardiovascular function: estrogen as key player. Microcirculation 11: 9-38, 2004 https://doi.org/10.1080/10739680490266162
  39. Simoncini T, Mannella P, Fornari L, Caruso A, Varone G, Genazzani AR. Genomic and non-genomic effects of estrogens on endothelial cells. Steriods 69: 537-542, 2004 https://doi.org/10.1016/j.steroids.2004.05.009
  40. Green S, Walter P, Kumar V, Krust, Bormert JM, Argos P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 320: 134-139, 1986 https://doi.org/10.1038/320134a0
  41. Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 392: 49-53, 1996 https://doi.org/10.1016/0014-5793(96)00782-X
  42. Venkov CD, Rankin AB, Vaughan DE. Identification of authentic estrogen receptor in cultured endothelial cells. A potential mechanism for steroid hormone regulation of endothelial function. Circulation 94: 727-733, 1994
  43. Karas RH, Patterson BL, Mendelsohn ME. Human vascular smooth muscle cells contain functional estrogen receptor. Circulation 89: 1943-195, 1994
  44. Sudhir K, Chou TM, Messina LM, Hutchison SJ, Korach KS, Chatterjee K. Endothelial dysfunction in a man with disruptive mutation in oestrogen-receptor gene. Lancet 349: 146-1147, 1997 https://doi.org/10.1016/S0140-6736(97)22003-9
  45. Sudhir K, Chou TM, Chatterjee K, Smith EP, Williams TC, Kane JP. Premature coronary artery disease associated with a disruptive mutation in the estrogen receptor gene in a man. Circulation 96: 3773-3777, 1997
  46. Pare G, Krust A, Karas RH, Dupont S, aronovitz M, Chambon P. Estrogen receptor-alpha mediates the protective effects of estrogen against vascular injury. Circ Res 90: 1087-1092, 2002 https://doi.org/10.1161/01.RES.0000021114.92282.FA
  47. Zhu Y, Bian Z, Lu P, Karas RH, Bao L, Cox D. Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta. Science 295: 505-508, 2002 https://doi.org/10.1126/science.1065250
  48. Truss M, Beato M. Steroid hormone receptors: interaction with deoxyribonucleic acid and transcription factors. Endocr Rev 14: 459-479, 1993
  49. Simoncini T, Fornari L, Mannella P, Varone G, Caruso A, Liao JK, Genazzani AR. Novel non-transcriptional mechanisms for estrogen receptor signaling in the cardiovascular system. Interaction of estrogen receptor ${\alpha}$ with phosphatidylinositol 3-OH kinase. Steriods 67: 935-939, 2002 https://doi.org/10.1016/S0039-128X(02)00040-5
  50. Xie W, Herschman HR. Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet-derived growth factor and serum. J Biol Chem 271: 31742-31748, 1996 https://doi.org/10.1074/jbc.271.49.31742
  51. Guan Z Buckman SY, Miller BW, Springer LD, Morrison AR. Interleukin-l beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MARK signal pathways in rat renal mesangial cells. J Biol Chem 273: 28670-28676, 1998 https://doi.org/10.1074/jbc.273.44.28670
  52. Whitmarsh AJ, Sharrocks AD, Davis RJ. Integration of MAP kinase signal transduction pathways at the serum response element. Science 269: 403-407, 1995 https://doi.org/10.1126/science.7618106
  53. Cobb MH, Goldsmith EJ. How MAP kinases are regulated. J Biol Chem 270: 14843-14846, 1995 https://doi.org/10.1074/jbc.270.25.14843
  54. Xie W, Herschman HR. Transcriptional regulation of prostaglandin synthase 2 gene expression by platelet-derived growth factor and serum. J Biol Chem 271: 31742-31748, 1996 https://doi.org/10.1074/jbc.271.49.31742
  55. Guan Z, Buchman SY, Miller BW, Springer LD, Morrison AR. Interleukin-1 beta-induced cyclooxygenase-2 expression requires activation of both c-Jun $NH_{2}$-terminal kinase and p38 MARK signal pathways in rat renal mesangial cells. J Biol Chem 273: 28670-28676, 1998 https://doi.org/10.1074/jbc.273.44.28670
  56. Degousee N, Martindale J, Stefanski E, Cieslak M, Lindsay TF, Fish JE, Marsden PA, Threrauf DJ, Glembotski CC, Rubin BB. MAP kinase kinase 6-p38 MAP kinase signaling cascade regulates cyclooxygenase-2 expression in cardiac myocytes in vitro and in vivo. Circ Res 92: 757-764, 2003 https://doi.org/10.1161/01.RES.0000067929.01404.03
  57. Adderley SR, Fitzgerald DJ. Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2. J Biol Chem 274: 5038-5046, 1999 https://doi.org/10.1074/jbc.274.8.5038
  58. Sirois J, Levy LO, Simmons DL, Richards JS. Characterization and hormonal regulation of the promter of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells: identification of functional and protein-binding regions. J Biol Chem 268: 12199-12206, 2000
  59. Wadleigh DJ, Reddy ST, Kopp E, Ghosh S, Herschman HR. Transcriptional activation of the cyclooxygenase-2 gene in endotoxin-treated RAW 264.7 macrophages. J Biol Chem 275: 6259-6266, 2000 https://doi.org/10.1074/jbc.275.9.6259
  60. Mayorga M, Bahi N, Ballester M, Comella JX, Sanchis D. Bcl-2 is a key factor for cardiac fibroblast resistance to programmed cell death. J Biol Chem 279: 34882-34889, 2004 https://doi.org/10.1074/jbc.M404616200
  61. Mori-Abe A, Tsutsumi S, Takahashi K, Toya M, Yoshida M, Du B, Kawagoe J, Nakahara K, Takahashi T, Ohmichi M, Kurachi H. Estrogen and raloxifene induce apoptosis by activating p38 mitogen-activated protein kinase cascade in synthetic vascular smooth muscle cells. J Endocrinol 178: 417-426, 2003 https://doi.org/10.1677/joe.0.1780417
  62. Badawi AF, Liu Y, Eldeen MB, Morrow W, Razak ZR, Maradeo M, Badr MZ. Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate. Carcinogenesis 25: 1681-1688, 2004 https://doi.org/10.1093/carcin/bgh176
  63. Prescott SM, Fitzpatrick FA. Cyclooxygenase-2 and carcinogenesis. Biochim Biophy Acta 1470: M69-M78, 2000
  64. Zha S, Yegnasubramanian V, Nelson WG, Isaacs WB, De Marzo AM. Cyclooxygenases in cancer: progress and perspective. Cancer Letters 215: 1-20, 2004 https://doi.org/10.1016/j.canlet.2004.06.014