Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Involvement of Peroxynitrite in NO Donor-Induced HO-1 Expression in Rat Articular Chondrocytes

흰쥐 관절연골세포에서 NO donor에 의해 유도된 HO-1 발현에서 peroxynitrite의 관련성 연구

  • Song, Ju-Dong (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Kim, Kang-Mi (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Kim, Jong-Min (Department of Anatomy and Cell Biology, Dong-A University College of Medicine) ;
  • Yoo, Young-Hyun (Department of Anatomy and Cell Biology, Dong-A University College of Medicine) ;
  • Park, Young-Chul (Department of Microbiology and Immunology, Pusan National University School of Medicine)
  • 송주동 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 김강미 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 김종민 (동아대학교 의과대학 해부학교실) ;
  • 유영현 (동아대학교 의과대학 해부학교실) ;
  • 박영철 (부산대학교 의학전문대학원 미생물학 및 면역학교실)
  • Received : 2011.01.13
  • Accepted : 2011.02.23
  • Published : 2011.04.30
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Abstract

Nitric oxide (NO) donors are a potent inducer of heme oxygenase-1 (HO-1). However, it is unclear whether or not HO-1 expression induced by NO donors is a direct consequence of NO released by NO donors. Here, we investigated the effects of NO donors on the expression of HO-1 in primary rat articular chondrocytes. NO donors (SIN-1, SNAP, and SNP) significantly induced the accumulation of HO-1 protein accompanied by an increase in HO-1 mRNA. NO donor-induced HO-1 expression exerted cytoprotection against NO and/or superoxide-induced cell death. Guanylate cyclase signaling was not associated with Nrf2 and HO-1 expression in NO donor-treated chondrocytes. Interestingly, NO scavenger carboxy-PTIO and SOD mimetic TEMPOL markedly inhibited NO donor-induced HO-1 expression in chondrocytes. In addition, NO donor-induced HO-1 expression was completely abrogated by the peroxynitrite scavenger MnTBAP. Since peroxynitrite can be physiologcally formed in the cell through reaction of NO with superoxide, we analyzed whether or not peroxynitrite could directly induce HO-1 expression in chondrocytes. Peroxynitrite treatment in chondrocytes evoked doseand time-dependent Nrf2 and HO-1 expression. These results indicate that HO-1 expression induced by NO donors in rat articular chondrocytes is due to NO-mediated peroxynitrite rather than NO.

Nitric oxide (NO) donors는 heme oxygenase-1 (HO-1)의 강력한 유도제이다. 그러나 NO donors에 의한 HO-1의 발현이 NO donor에 의해 방출되는 NO에 의한 직접적인 영향인지는 불분명하다. 본 연구에서 흰쥐의 무릎으로부터 분리 배양한 관절연골세포에서 HO-1의 발현에 NO donors의 영향을 조사하였다. NO donors (SIN-1, SNAP 그리고 SNP)는 HO-1의 mRNA와 단백질의 합성을 크게 증가시켰다. 그리고 NO의 표적 분자인 guanylate cyclase와 protein kinase G의 관련성을 살펴본 결과, NO donors에 의한 Nrf2와 HO-1의 발현증가와는 무관한 것으로 보였다. 흥미롭게도, NO scavenger인 carboxy-PTIO와 SOD mimetic TEMPOL은 NO donors에 의한 HO-1의 발현을 억제하였다. 게다가, peroxynitrite scavenger인 MnTBAP에 의해서도 Nrf2와 HO-1의 발현이 완전히 억제되었다. Peroxynitrite는 NO와 superoxide의 반응에 의해 세포 내에서 자연적으로 형성되는 물질이므로 peroxynitrite가 관절연골세포에서 HO-1의 발현에 직접적인 영향을 주는지를 관찰하였다. 관절연골세포에 peroxynitrite를 처리한 결과, 시간과 농도 의존적으로 Nrf2와 HO-1의 발현을 크게 증가시켰다. 본 실험 자료 는 NO donors에 의한 HO-1의 발현증가는 방출되는 NO의 직접적인 영향이라기 보다는 NO와 superoxide의 반응으로 형성되는 peroxynitrite에 의해 유도된다는 것을 시사한다.

Keywords

References

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