Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
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4-Nonylphenol Increased NO Synthesis via a Non-genomic Action in GH3 Cells

뇌하수체 세포인 GH3세포에서 non-genomic action을 통한 Nonylphenol의 nitric oxide 증진효과

  • 이경진 (전남대학교 자연과학대학 생물학과) ;
  • 최철웅 (진주 국제대학교 식품과학부) ;
  • 손현정 (전남대학교 자연과학대학 생물학과) ;
  • 정백진 (전남대학교 자연과학대학 생물학과) ;
  • 문소희 (전남대학교 자연과학대학 생물학과) ;
  • 이황희 (전남대학교 자연과학대학 생물학과) ;
  • 이종빈 (진주 국제대학교 식품과학부)
  • Published : 2003.12.01
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Abstract

본 연구는 환경호르몬(endocrine disruptors)으로 분류되었으며, 에스트로젠 화합물의 특성을 지닌 4-Nonylphenol (NP)이 설치류 Pituitary 세포 중 성장호르몬을 분비하는 GH3 세포의 Nitric oxide(NO)을 증가시키는 작용기전을 규명코자 수행되었다 먼저 GH3세포에 NP처리 농도에 따른 NO의 생성을 측정한 결과 NP처리농도 의존적으로 증가시켰다. 이러한 NO의 증가가 genomic action인지를 확인하기 위해 GH3세포의 NO를 증가시키는 효소인 neuronal oxide synthase의 단백질량을 측정한 결과 GH3세포에서 NP에 의한 nNOS의 단백질의 변화는 없었다. 에스트로젠 화합물인 NP가 에스트로젠 리셉터 (ER)와의 관계를 조사하기 위해 ER억제제(ICI 168,780)클 처리한 경우 NP에 의해 증가한 NO가 감소하였다. 또한 유전자 전사억제제인 actinomycin D 및 단백질 발현 억제제인 cycloheximide을 처리한 경우는 NP에 의한 NO 증가억제효과가 없었다. 이러한 결과를 종합해 볼 때 GH3 세포에서 NP는 ER을 매개한 non-genomic action에 의해 NO를 증가키는 것으로 사료된다.

Keywords

References

  1. Chaves MC, Ribeiro RA and Rao VSN. Possible involvement of nitric oxide in estrogen-induced uterine edema in the immature rat, Brazil J. Med. Biol. Res. 1993; 26 : 853-857
  2. Chen Z, Yuhannna IS, Galcheva-Gargova Z, Karas RH, Mendelsohn ME and Skaul PW. Estrogen receptor a mediates nongenomic activation of eNOS by estrogen, J. Clin. Invest. 1999a; 103: 401-406 https://doi.org/10.1172/JCI5347
  3. Chen ZY, Su YL, Lau CW, Law WI and Huang Y. Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery, Eur. J. Pharmacol. 1999b; 374: 41-47 https://doi.org/10.1016/S0014-2999(99)00291-5
  4. Cho MM, Ziats NP, Pal D, Utian WH and Gorodeski Gl. Estrogen modulates paracellular permeability of human endothelial cells by eNOS- and iNOS-related mechanisms, Am. J. Physiol. 1999; 276: C337-C349 https://doi.org/10.1152/ajpcell.1999.276.2.C337
  5. Choi CY, Kim JY, Kim YS, Chung YC, Hahm KS and Jeong HG. Augmentation of macrophage functions by an aqueous extract isolated from Platycodon grandiflorum, Cancer Lett. 2001; 166: 17-25 https://doi.org/10.1016/S0304-3835(01)00440-2
  6. Colborn T, vom Saal FS and Soto AM. Developmental effects of endocrine-disrupting chemicals in wildlife and humans, Environ. Health Perspect. 1993; 101: 378-384 https://doi.org/10.2307/3431890
  7. Drazen D., Klein SL, Burnett AL, Wallach EE, Crone JK, Huang PL and Nelson RJ. Reproductive function in female mice lacking the gene for endothelial nitric oxide synthase, Nitric Oxide 1999; 3: 366-374 https://doi.org/10.1006/niox.1999.0251
  8. Ellman C, Corbett JA, Misko TP, McDaniel M and Beckerman KP. Nitric oxide mediates interleukin-l-induced cellular cytotoxicity in the rat ovary. A potential role for nitric oxide in the ovulatory process, J. Clin. Invest. 1993; 92: 3053-3056 https://doi.org/10.1172/JCI116930
  9. Gutendorf B and Westendorf J. Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens, Toxicology 2001; 166: 79-89 https://doi.org/10.1016/S0300-483X(01)00437-1
  10. Heck DE, Laskin JD, Zigman S and Troll W. NG-monomethyl-L-arginine inhibits Arbacia fertilization and differentiation, Biol. Bull. 1994; 187: 248-249 https://doi.org/10.1086/BBLv187n2p248
  11. Hiroi H, Tsutsumi O, Momoeda M, Takai Y, Osuga Y and Takatani Y. Differential interactions of bisphenol A and 17-estradiol with estrogen receptor a (ER) and ER, Endocr. J. 1999; 46: 773-778 https://doi.org/10.1507/endocrj.46.773
  12. Hishikawa K, Nakaki T, Marumo T, Suzuki H, Kato R and Saruta T. Upregulation of endothelial nitric oxide synthase by estradiol in human aortic endothelial cells, FEBS Lett. 1995; 360: 291-293 https://doi.org/10.1016/0014-5793(95)00124-R
  13. Hossaini A, Dalgaard M, Vinggaard AM, Frandsen H and Larsen JJ. In utero reproductive study in rats exposed to nonylphenol, Reprod. Toxicol. 2001; 15: 537-543 https://doi.org/10.1016/S0890-6238(01)00155-1
  14. Hyder SM, Kirkland JL, Loose-Mitchell DS, Ma 'kela' S and Stancel GM. In: Naz, R.K. (Ed.), Endocrine Disrupters. CRC Press, Boca Raton, FL, pp. 165-186, 1999
  15. Krishnan AV, Stathis P, Permuth SF, Tokes L and Feldman D. Bisphenol A: an estrogenic substance is released from polycarbonate flasks during autoclaving, Endocri-nology 1993; 132: 2279-2286 https://doi.org/10.1210/en.132.6.2279
  16. Laws SC, Carey SA, Ferrell JM, Bodman GJ and Cooper RL. Estrogenic activity of octylphenol, nonyphenol, bisphenol A and methoxychlor in rats, Toxicol. Sci. 2000; 54: 154-167 https://doi.org/10.1093/toxsci/54.1.154
  17. Lemos VS, Freitas MR, Muller B, Lino YD, Queiroga CE and Cortes SF. Dioclein, a new nitric oxide- and endothelium-dependent vasodilator flavonoid, Eur. J. Pharmacal. 1999; 386: 41-46 https://doi.org/10.1016/S0014-2999(99)00747-5
  18. Loose-Mitchell DS, Chiappetta C, Stancel GM. Estrogen regulation of c-fos messenger ribonucleic acid, Mol. Endocrinol. 1988; 2: 946-950 https://doi.org/10.1210/mend-2-10-946
  19. MacRitchie AN, Jun SS, Chen Z, German Z, Yuhanna IS, Sherman TS and Shaul PW. Estrogen upregulates endo-thelial nitric oxide synthase gene expression in fetal pulmonary endothelium, Circ. Res. 1997; 81: 355-362 https://doi.org/10.1161/01.RES.81.3.355
  20. Muller AMF, Makropoulos V and Bolt HM. Toxicological aspects of oestrogen-mimetic xenobiotics present in the environment, Toxicol. Ecotoxicol. News 1995; 2: 68-73
  21. Nimrod AC and Benson WH. Estrogenic effects of alkyl-phenol ethoxylates, Crit. Rev. Toxicol. 1996; 26: 335-364 https://doi.org/10.3109/10408449609012527
  22. Purcell TL, Given R, Chwalisz K and Garfield RE. Nitric oxide synthase distribution during implantation in the mouse, Mol. Hum. Reprod. 1999; 5: 467-475 https://doi.org/10.1093/molehr/5.5.467
  23. Sengoku K, Takuma N, Horikawa M, Tsuchiya K, Komori H, Sharifa D, Tamate K and Ishikawa M. Requirement of nitric oxide for murine oocyte maturation, embryo development, and trophoblast outgrowth in vitro, Mol. Reprod. Dev. 2001; 58: 262-268 https://doi.org/10.1002/1098-2795(200103)58:3<262::AID-MRD3>3.0.CO;2-8
  24. Sharpe RM, Fisher JS, Millar MM, Jobling S and Sumpter JP. Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production, Environ. Health Perspect. 1995; 103: 1136-1143 https://doi.org/10.2307/3432610
  25. Steinmetz R, Brown NG, Allen DL, Bigsby R., Ben-Jonat-han N. The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo, Endocrinology 1997; 138: 1780-1786 https://doi.org/10.1210/en.138.5.1780
  26. Weisz A, Bresciani F. Estrogen induces expression of c-fos and c-myc protooncogenes in rat uterus, Mol. Endocrinol. 1988; 2: 816-824 https://doi.org/10.1210/mend-2-9-816
  27. White R, Jobling S and Hoare JP. Sumpter and MG Parker, Environmentally persistent alkylphenol compounds are estrogenic, Endocrinology 1994; 135: 175-182 https://doi.org/10.1210/en.135.1.175