임신 자궁 내막에서 Two-pore Domain 칼륨 통로의 발현 변화

Alteration in Two-pore Domain K$^+$ Channel Expression in Endometrium of Pregnant Korean Cattle

  • 최창용 (농촌진흥청 국립축산과학원) ;
  • 탁현민 (경상대학교 의학전문대학원 생리학교실/건강과학연구원) ;
  • 김창운 (성균관대학교 삼성창원병원) ;
  • 한재희 (경상대학교 의학전문대학원 생리학교실/건강과학연구원) ;
  • 강다원 (경상대학교 의학전문대학원 생리학교실/건강과학연구원)
  • Choe, Chang-Yong (National Institute of Animal Science, RDA) ;
  • Tak, Hyun-Min (Department of Physiology, Gyeongsang National University School of Medicine and Institute of Health Sciences) ;
  • Kim, Chang-Woon (Samsung Changwon Hospital) ;
  • Han, Jae-Hee (Department of Physiology, Gyeongsang National University School of Medicine and Institute of Health Sciences) ;
  • Kang, Da-Won (Department of Physiology, Gyeongsang National University School of Medicine and Institute of Health Sciences)
  • 투고 : 2011.08.08
  • 심사 : 2011.08.30
  • 발행 : 2011.09.30

초록

임신의 성립 및 유지에 중요한 자궁 내막과 호르몬의 변화는 생식기관에서 발현되는 K$_{2P}$ 통로의 발현을 변화시킬 수 있다. 본 연구는 한우의 임신 자궁 내막에서 K$_{2P}$ 통로의 발현 변화가 나타나는지 그리고 프로게스테론에 의해 그 발현량이 변화되는지를 확인하고자 수행하였다. 역전사중합효소 중합반응과 웨스턴블닷 분석을 통하여 임신한 한우의 자궁 내막에서 mRNA와 단백질의 발현 변화를 조사하였다. TREK-1을 제외한 K$_{2P}$ 통로의 mRNA 발현량이 임신 자궁 내막에서 변화되었다. mRNA가 크게 변화되는 TASK-3, TREK-2, TRAAK 및 TRESK의 단백발현 변화량을 임신 자궁 내막에서 확인하였는데, TREK-2와 TRESK만 mRNA 발현 변화 양상과 동일하게 임신 자궁 내막에서 각각 7.9배, 2배 증가하였다. 자궁 내막세포에 프로게스테론(10 ${\mu}g$/mL)을 처리하였을 때 TREK-2와 TRESK는 자궁 내막 조직에서 보여준 결과와 유사하게 단백 발현량이 각각 10배, 6배 증가하였다. 이상의 결과로부터 K$_{2P}$ 통로, 특히 TREK-2와 TRESK는 프로게스테론 변화에 의해 임신 자궁 내막에서 발현량이 증가할 것으로 생각된다. 그리고 증가된 TREK-2와 TRESK는 임신에 의해 유발되는 생리학적 변화를 조절하는데 기여할 것으로 생각된다.

Endometrium undergoing hormonal change plays important roles in preparation for implantation, fetal growth, and well-being. During pregnancy, cellular remodeling and hormonal changes in endometrium could change two-pore domain K$^+$ channel (K$_{2P}$) expression. This study was performed to identify whether K$_{2P}$ channel expression is changed in endometrium of pregnant Korean cattle, and whether the expression level is modulated by progesterone treatment. We investigated changes in the mRNA and protein expressions of K$_{2P}$ channel in pregnant endometrium using RT-PCR and Western blot analyses. The expression levels of all K$_{2P}$ channel mRNAs tested in this study, except that of TREK-1, were changed in the pregnant endometrium. mRNA levels of TASK-3 and TRAAK were significantly down-regulated, whereas those of TREK-2 and TRESK were up-regulated in the pregnant endometrium. In parallel with the RT-PCR results, Western blot analysis revealed up-regulations of TREK-2 (7.9-fold) and TRESK (2-fold) proteins levels in the pregnant endometrium. In addition, TREK-2 and TRESK protein levels were up-regulated in bovine endometrial cells by progesterone treatment (10 ${\mu}g$/ml). From these results, we suggest that the up-regulation of TREK-2 and TRESK by progesterone may contribute to the regulation of physiological changes during pregnancy.

키워드

참고문헌

  1. Bai X, Bugg GJ, Greenwood SL, Glazier JD, Sibley CP, Baker PN, Taggart MJ and Fyfe GK. 2005a. Expression of TASK and TREK, two-pore domain $K^{+}$channels, in human myometrium. Reproduction 129:525-530. https://doi.org/10.1530/rep.1.00442
  2. Bai X, Greenwood SL, Glazier JD, Baker PN, Sibley CP, Taggart MJ and Fyfe GK. 2005b. Localization of TASK and TREK, two-pore domain $K^{+}$ channels, in human cytotrophoblast cells. J. Soc. Gynecol. Investig. 12:77-83. https://doi.org/10.1016/j.jsgi.2004.08.004
  3. Bai X, Lacey HA, Greenwood SL, Baker PN, Turner MA, Sibley CP and Fyfe GK. 2006. TASK channel expression in human placenta and cytotrophoblast cells. J. Soc. Gynecol. Investig. 13:30-39. https://doi.org/10.1016/j.jsgi.2005.10.005
  4. Besana A, Robinson RB and Feinmark SJ. 2005. Lipids and two-pore domain $K^{+}$ channels in excitable cells. Prostaglandins Other Lipid Mediat. 77:103-110. https://doi.org/10.1016/j.prostaglandins.2004.10.005
  5. Borna S and Sahabi N. 2008. Progesterone for maintenance tocolytic therapy after threatened preterm labour: A randomised controlled trial. Aust. N. Z. J. Obstet. Gynaecol. 48: 58-63 https://doi.org/10.1111/j.1479-828X.2007.00803.x
  6. Enyeart JJ, Xu L, Danthi S, and Enyeart JA. 2002. An ACTHand ATP-regulated background $K^{+}$ channel in adrenocortical cells is TREK-1. J. Biol. Chem. 277:49186-49199. https://doi.org/10.1074/jbc.M207233200
  7. Gellersen B, Fernandes, MS and Brosens JJ. 2009. Non-genomic progesterone actions in female reproduction. Hum. Reprod. Update 15:119-138
  8. Hur CG, Choe C, Kim GT, Cho SK, Park JY, Hong SG, Han J and Kang D. 2009. Expression and localization of twopore domain $K^{+}$ channels in bovine germ cells. Reproduction 137:237-244. https://doi.org/10.1530/REP-08-0035
  9. Kang D, Han J and Kim D. 2006. Mechanism of inhibition of TREK-2 (K2P10.1) by the Gq-coupled M3 muscarinic receptor. Am. J. Physiol. Cell Physiol. 291:649-656. https://doi.org/10.1152/ajpcell.00047.2006
  10. Kelley BG and Mermelstein PG. 2011. Progesterone blocks multiple routes of ion flux. Mol. Cell. Neurosci. 48:137-141. https://doi.org/10.1016/j.mcn.2011.07.002
  11. Kim D. 2003. Fatty acid-sensitive two-pore domain $K^{+}$ channels. Trends Pharmacol. Sci. 24:648-654. https://doi.org/10.1016/j.tips.2003.10.008
  12. Kim D. 2005. Physiology and pharmacology of two-pore domain potassium channels. Curr. Pharm. Des. 11:2717-2736. https://doi.org/10.2174/1381612054546824
  13. Kim EJ, Kang D and Han J. 2011. Baicalein and wogonin are activators of rat TREK-2 two-pore domain $K^{+}$ channel. Acta Physiol. 202:185-92 https://doi.org/10.1111/j.1748-1716.2011.02263.x
  14. Kunzelmann, K. 2005. Ion channels and cancer. J. Membr. Biol. 205:159-173. https://doi.org/10.1007/s00232-005-0781-4
  15. Rice A and Chard T. 1998. Cytokines in implantation. Cytokine Growth Factor Rev. 9:287-296. https://doi.org/10.1016/S1359-6101(98)00020-3
  16. Sanders KM and Koh SD. 2006. Two-pore-domain potassium channels in smooth muscles:new components of myogenic regulation. J. Physiol. 570:37-43. https://doi.org/10.1113/jphysiol.2005.098897
  17. Sano Y, Inamura K, Miyake A, Mochizuki S, Kitada C, Yokoi H, Nozawa K, Okada H, Matsushime H and Furuichi K. 2003. A novel two-pore domain $K^{+}$channel, TRESK, is localized in the spinal cord. J. Biol. Chem. 278:27406-27412. https://doi.org/10.1074/jbc.M206810200
  18. Shen Z, Yang Q and You Q. 2009. Researches toward potassium channels on tumor progressions. Curr. Top. Med. Chem. 9: 322-329. https://doi.org/10.2174/156802609788317874
  19. Strunker T, Goodwin N, Brenker C, Kashikar ND, Weyand I, Seifert R and Kaupp UB. 2011. The CatSper channel mediates progesterone-induced $Ca^{2+}$ influx in human sperm. Nature 471:382-386. https://doi.org/10.1038/nature09769
  20. Talley EM, Sirois JE, Lei Q and Bayliss DA. 2003. Two-pore- Domain (KCNK) potassium channels: Dynamic roles in neuronal function. Neuroscientist 9:46-56. https://doi.org/10.1177/1073858402239590
  21. Tichenor JN, Hansen ET and Buxton IL. 2005. Expression of stretch-activated potassium channels in human myometrium. Proc. West. Pharmacol. Soc. 48:44-48.
  22. Wareing M, Bai X, Seghier F, Turner CM, Greenwood SL, Baker PN, Taggart MJ and Fyfe GK. 2006. Expression and function of potassium channels in the human placental vasculature. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291: 437-446. https://doi.org/10.1152/ajpregu.00040.2006
  23. Xiao G, Wei J, Yan W, Wang W and Lu Z. 2008. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: A randomized controlled trial. Crit. Care. 12:61.
  24. 강다원, 김은숙, 양혜영, 최창용, 한재희. 2007. 한우의 자궁내막세포에서 발현되는 two-pore domain 포타슘 통로. 한국수정란이식학회지 22:149-154.