Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Extract of Rubus coreanus Fruits Increases Expression and Activity of Endothelial Nitric Oxide Synthase in the Human Umbilical Vein Endothelial Cells

복분자 추출물에 의한 내피세포 NO 합성효소의 활성과 발현 증가

  • Yoon, Hyun-Joong (Department of Biochemistry, Medical School and Research Institute of Medical Science, Chonnam National University) ;
  • Park, Soo-Young (Department of Obstetrics and Gynecology, Medical School and Research Institute of Medical Science, Chonnam National University) ;
  • Oh, Sung-Tack (Department of Obstetrics and Gynecology, Medical School and Research Institute of Medical Science, Chonnam National University) ;
  • Lee, Kee-Young (Department of Biochemistry, Medical School and Research Institute of Medical Science, Chonnam National University) ;
  • Yang, Sung-Yeul (Department of Biochemistry, Medical School and Research Institute of Medical Science, Chonnam National University)
  • 윤현중 (전남대학교 의과대학 생화학교실, 의과학연구소) ;
  • 박수영 (전남대학교 의과대학 산부인과학교실, 의과학연구소) ;
  • 오성택 (전남대학교 의과대학 산부인과학교실, 의과학연구소) ;
  • 이기영 (전남대학교 의과대학 생화학교실, 의과학연구소) ;
  • 양성렬 (전남대학교 의과대학 생화학교실, 의과학연구소)
  • Received : 2010.11.17
  • Accepted : 2010.01.04
  • Published : 2011.01.30
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Abstract

This study aimed to investigate the effects of water extract of Rubus coreanus (RCE) on the expression and activity of endothelial nitric oxide synthase (eNOS), as well as its signal transduction pathways in human umbilical vein endothelial cells (HUVECs). The specific inhibitors of NOS show RCE treatment increases NO production in HUVECs due to the up-regulation of eNOS rather than iNOS. The real-time expression level of eNOS mRNA was also increased upon RCE treatment in HUVECs. While a PKC-specific inhibitor, RO-317549, did not alter RCE-induced NO production in HUVECs, tamoxifen (estrogen receptor-specific inhibitor), PD98059 (ERK-specific inhibitor) and LY-294002 (PI3K/Akt-specific inhibitor) did have suppressive effects. Increased NO production by RCE seems to result from a higher level of active eNOS (pSer1177). Specifically, inhibition of ERK not only decreased the level of active eNOS, but also increased the inactive form of the enzyme (pThr495) in HUVECs. This study suggests that RCE treatment increases NO production in HUVECs due to the increased expression and activity of eNOS. It is also shown that RCE-induced eNOS activation occurs partly through the binding of RCE to the estrogen receptor, along with ERK and PI3K/Akt-dependent signal transduction pathways. In addition, the regulatory binding proteins of eNOS including Hsp90 and caveolin-1 were related to these effects of RCE on eNOS activity in HUVECs.

본 연구는 복분자의 수용성 추출물(RCE) 이 배양된 제대정맥내피세포에서 내피세포 NO 합성 효소(eNOS)의 발현과 활성에 미치는 효과를 연구하고, 이러한 RCE의 효과가 어떤 신호전달 과정을 거치는지를 밝히기 위한 것이다. 연구에 따르면 RCE가 제대정맥내피세포에서 NO의 생성을 증가시키는데 이는 iNOS 보다는 eNOS의 활성화에 의한 것임을 이들의 특이 억제제를 사용한 실험으로 확인할 수 있었다. 나아가 eNOS에 의한 NO 생성 증가는 이 효소의 활성 증가뿐만 아니라 mRNA 수준에서의 발현증가에도 기인함을 확인할 수 있었다. PKC-특이억제제인 RO-317549는 RCE에 의한 NO 생성의 증가에 별다른 영향을 주지 않았으나, 에스트로젠 수용체-특이 억제제인 Tamoxifen, ERK-특이 억제제인 PD98059와 PI3K/Akt-특이 억제제인 LY-294002는 제대정맥내피세포에서 RCE에 의해 증가된 NO 생성을 억제하였으며, 이는 두 저해제가 eNOS의 활성형인 pSer1177의 양을 감소시키며, 특히 PD98059는 비활성형인 pThr495의 양도 증가시키기 때문임을 알 수 있었다. 이상의 결과로써, 복분자 수추출물은 사람의 제대정맥내피세포에서 NO 생성을 증가시키며, 이는 eNOS의 발현을 증가시킬 뿐만 아니라, ERK와 PI3K/Akt의 신호전달과정을 거쳐서 eNOS의 활성도 증가시키기 때문임을 확인할 수 있었다.

Keywords

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