Journal of Animal Science and Technology

Korean Society of Animal Sciences and Technology (한국축산학회)
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Relationships of the Lithium-Induced Growth Inhibition of C6 Rat Glioma Cell to Expression of the Insulin-like Growth Factor System Components

C6 Rat Glioma Cell에서 리튬에 의한 성장 억제와 Insulin-like Growth Factor System Components의 발현과의 관계

  • Kim, I.A. (Regional Animal Industry Research Center, Jinju National University, Department of Animal Resources Technology) ;
  • Jin, E.J. (Regional Animal Industry Research Center, Jinju National University, Department of Animal Resources Technology) ;
  • Cho, E.J. (Regional Animal Industry Research Center, Jinju National University, Department of Animal Resources Technology) ;
  • Sohn, S.H. (Regional Animal Industry Research Center, Jinju National University, Department of Animal Resources Technology) ;
  • Lee, C.Y. (Regional Animal Industry Research Center, Jinju National University, Department of Animal Resources Technology)
  • 김인애 (진주상업대학교 동물소재공학과. 동물생명산업 지역협력연구센터) ;
  • 진은정 (진주상업대학교 동물소재공학과. 동물생명산업 지역협력연구센터) ;
  • 조은정 (진주상업대학교 동물소재공학과. 동물생명산업 지역협력연구센터) ;
  • 손시환 (진주상업대학교 동물소재공학과. 동물생명산업 지역협력연구센터) ;
  • 이철영 (진주상업대학교 동물소재공학과. 동물생명산업 지역협력연구센터)
  • Published : 2004.08.31
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Abstract

The insulin-like growth factor(IGF) system, consisting of IGFs-I and -II ligands and their receptors and six IGF-binding proteins(IGFBPs), plays an important role in survival, proliferation and differentiation of a variety of cell types. Lithium is a known modulator of survival and proliferation of many cell types in vitro. The present study was undertaken to investigate the relationship between LiCI-induced changes in cell survival and growth and the expression of the IGF system components in C6 rat glioma cell line which, besides IGF-I and its receptor, is known to express IGFBP-3 as its major IGF carrier. When C6 cells were cultured for 24h in the absence or presence of 2mM or 5mM LiCl in a 10% serwn-containing medium, the viability and the number of cells were not affected by added lithium. In 72-h culture, however, C6 cells clearly exhibited a dose-dependent response to added LiCl. The cells cultured for 72h in the presence of 0, 2mM and 5mM LiCl exhibited a typical mitotic, a growth-arrested and an apoptotic appearances, respectively. Moreover, the apoptotic cells were accompanied by reduced expression of IGF-I, IGF-I receptor and IGFBP-3 as examined by semi-quantitative reverse transcription-polymerase chain reaction. Interestingly, blockade of IGFBP-3 mRNA translation by addition of 101${\mu}M$ IGFBP-3 anti-sense oligodeoxyribonucleotide in serum-free, 24-h culture resulted in a decrease in the number of cells as well as relative abundance of the target mRNA. In summary, results suggest that the cytotoxic effect of lithium in C6 cell is likely to be mediated, in part, by suppression by this agent of the expression of the IGF system components. In this regard, IGFBP-3 may play at least a 'permissive' role in normal proliferation of this cell.

Insulin-like growth factors(IGF)s-I과 -II ligands와 이들의 receptors 및 6종류의 IGF-binding proteins(IGFBPs)로 구성된 IGF systim은 여러 종류의 세포의 생존, 증식 및 분화에 있어서 매우 중요한 역할을 한다. 리튬은 in vitro에서 여러 종류의 세포의 생존과 증식의 조절제로 알려져 있다. 본 연구는 IGF-I, IGF-I receptor 및 IGF carrier로서 주로 IGFBP-3를 발현하는 rat C6 glioma cell에서 LiCl로 유도된 세포 생존 및 증식의 변화와 IGF system components의 발현간의 관계를 구명하고자 수행되었다. 10%혈청을 함유하는 배양액에서 0, 2mM, 혹은 5mM LiCl을 첨가하여 C6 cell을 24시간 배양했을 시 세포의 생존률과 세포 수는 리튬 첨가에 의해 영향을 받지 않았다. 그러나 72시간 배양 했을 때 C6 cell은 명백히 리튬의 첨가수준에 따라 반응하였다. 0, 2m, 5mM LiCl 첨가수준에서 72시간 배양한 C6 cell은 각각 전형적인 세포분열, 세포분열 중지 및 세포사멸 양상을 보였다. 더욱이 사멸돼가는 세포는 reverse transcription-polymerase chain reaction으로 조사한 IGF-I, IGF receptor 및 IGFBP-3의 발현수준이 저하되었다. 흥미롭게도 혈청을 첨가하지 않은 배양조건 하에서 IGFBP-3에 대한 antisense oligodeoxyribonucleotide를 10${\mu}M$ 수준의로 첨가하여 배양했을 때도 표적 mRNA는 물론 세포 수도 줄었다. 종합하자면, C6 cell에서 리튬의 독성 효과의 일부는 이 제제에 의한 IGF system components의 발현 억제 효과에 의해 매개될 소지가 크다. 이러한 관점에서 IGRBP-3는 적어도 이 세포의 정상적인 증식을 위해 꼭 필요한(‘prrmissive') 역할을 할 수 있다는 점을 시사한다.

Keywords

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