Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
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The Role of GADD45 ${\beta}$ in Acute Myocardial Injury

급성 심근 손상에서 GADD45 ${\beta}$의 역할

  • Cho, Suk-Ki (Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, College of Medicine, Kyungpook National University) ;
  • Hong, Jong-Myeon (Department of Thoracic and Cardiovascular Surgery, Chungbuk National University Hospital, College of Medicine, Chungbuk National University) ;
  • Lee, Hak-Mo (Xenotransplantation Research Center, Clinical Research Institute, Seoul National University Hospital, Department of Cardiothoracic Surgery, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University) ;
  • Oh, Byong-Chul (Xenotransplantation Research Center, Clinical Research Institute, Seoul National University Hospital, Department of Cardiothoracic Surgery, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University) ;
  • Lee, Jae-Woong (Xenotransplantation Research Center, Clinical Research Institute, Seoul National University Hospital, Department of Cardiothoracic Surgery, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University) ;
  • Lee, Jeong-Ryul (Department of Thoracic and Cardiovascular Surgery, Seoul National University Children's Hospital, Seoul National University College of Medicine)
  • 조석기 (경북대학교 의과대학 경북대학교병원 흉부외과학교실) ;
  • 홍종면 (충북대학교 의과대학 충북대학교병원 흉부외과학교실) ;
  • 이학보 (서울대학교병원 임상의학연구소 이종장기 연구개발센터, 한림대학교 의과대학 한림대학교성심병원 흉부외과학교실) ;
  • 오병철 (서울대학교병원 임상의학연구소 이종장기 연구개발센터, 한림대학교 의과대학 한림대학교성심병원 흉부외과학교실) ;
  • 이재웅 (서울대학교병원 임상의학연구소 이종장기 연구개발센터, 한림대학교 의과대학 한림대학교성심병원 흉부외과학교실) ;
  • 이정렬 (서울대학교 의과대학 서울대학교어린이병원 흉부외과학교실)
  • Published : 2008.02.05
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Abstract

Background: A critical shortage of donor organs has necessitated an investigation of new strategies to increase the availability of additional organs available for human transplantation. We investigated the amount of apoptosis and expression of GADD45 ${\beta}$ in two groups, a GADD45 ${\beta}$-transfected group and untransfected group. Material and Method: The experimental groups consist of a control group (normal H9C2 cell line) and GADD45 ${\beta}$-transfected group. After injury of the each group, we evaluated the expression of GADD45 ${\beta}$ and the level of apoptosis in each group. Result: There was a significant increase in the expression of GADD45 ${\beta}$ in the GADD45 ${\beta}$-transfected group at 1 hour, 2 hours, and 3 hours after stimuli as compared with the control group. The amount of cardiac myoblast cell line apoptosis was significantly lower in the GADD45 ${\beta}$-transfected group as compared with the control group. The concentration of annex in in the GADD45 ${\beta}$-transfected group was significantly lower than that of the control. group after cell. injury. Conclusion: Transfection of a rat myoblast cell line with the GADD45 ${\beta}$ gene results in. decreased susceptibility to cell injury of human serum.

배경: 말기 장기부전 환자가 증가하고 있지만 장기 공여자의 수는 부족하여 이종장기 이식의 필요성이 대두되고 있다. 하지만 아직까지 이종장기 이식 시 발생하는 면역학적 거부 반응은 해결되지 못하고 있다. 이에 본 연구에서는 이종장기 이식에서의 거부반응 극복을 위한 노력의 일환으로 돼지 심장의 생체 외 인간 혈액 관류 모델을 만들어 장기에 대한 인간 혈액의 거부반응과 관련되어 발현되는 유전자에 대한 기능을 규명하고 거부반응 극복을 위한 활용방안을 연구하고자 하였다. 대상 및 방법: 돼지의 심장을 이용한 생체 외 인간혈액 관류 모델을 구축하여 인간 혈액을 관류시킨 뒤 시간의 경과에 따른 유전자 발현양상의 변화를 관찰하여 시간 변화에 다르게 발현되는 30여 개의 유전자 중하나인 GADD45 ${\beta}$를 찾았다. GADD45 ${\beta}$의 역할을 규명하고자 쥐의 심근 세포주 H9C2에 GADD45 ${\beta}$를 삽입시켜 과발현 시켰고 다양한 염증 및 거부반응 환경에서 이 유전자의 발현양상과 기능을 알아보고자 역전사 중합 효소 연쇄반응(RT-PCR)을 통해 GADD45 ${\beta}$의 발현 정도와 심근 세포주의 자멸사 정도를 평가하였다. 결과: 세포 손상을 주지 않은 상태에서는 GADD45 ${\beta}$를 삽입한 군에서 GADD45 ${\beta}$를 삽입하지 않은 군보다 GADD45 ${\beta}$의 발현이 증가하였으며 GADD45 ${\beta}$를 삽입하지 않은 군에서 세포 손상을 준 후 측정한 GADD45 ${\beta}$발현은 시간에 따라서 변화하는 양상을 보여 1시간까지는 증가하다가 그 이후에는 감소하였다. 세포에 인간 혈청으로 세포 손상을 주고 세포의 자멸사를 평가한 결과 GADD45 ${\beta}$를 삽입한 군에서 GADD45 ${\beta}$를 삽입하지 않은 군에 비해서 자멸사 정도가 적었다. 결론: GADD45 ${\beta}$를 삽입시킨 세포주는 인간의 혈청에 의한 세포 손상이 GADD45 ${\beta}$를 삽입시키지 않은 세포주 보다 자멸사의 정도가 적어 GADD45 ${\beta}$는 세포 손상에 의한 세포의 자멸사를 줄여 세포를 보호하는 역할을 하였다.

Keywords

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