초록 ▼

III. 연구개발의 내용 및 범위
1. 방사선 유도 스트레스반응에서 thioredoxin의 다중기능 연구
: Redox sensor로서의 작용 및 stress response에서의 역할
: Cell cycle regulator로서의 역할
2. 방사선자극에 대한 thioredoxin의 세포방호기전 규명
: 면역세포사멸 조절 및 생존유도인자로서 thioredoxin의 작용기전
: Thioredoxin을 통한 암세포의 방사선저항성 제어기전
3. 방사선유도 면역억제반응에 대한 thioredoxin의 조

III. 연구개발의 내용 및 범위
1. 방사선 유도 스트레스반응에서 thioredoxin의 다중기능 연구
: Redox sensor로서의 작용 및 stress response에서의 역할
: Cell cycle regulator로서의 역할
2. 방사선자극에 대한 thioredoxin의 세포방호기전 규명
: 면역세포사멸 조절 및 생존유도인자로서 thioredoxin의 작용기전
: Thioredoxin을 통한 암세포의 방사선저항성 제어기전
3. 방사선유도 면역억제반응에 대한 thioredoxin의 조절기전 확립
: 면역반응 유도 및 조절인자로서의 작용기작
: Th1/Th2 반응 조절인자로서의 역할과 작용기전 규명

Abstract ▼

Thioredoxin plays a major role in the control of cellular redox status. In addition to its defense function under oxidative stress, thioredoxin is now recognized for the wide spectrum activities in various biological processes including cell survival,
differentiation, apoptosis as well as immune-

Thioredoxin plays a major role in the control of cellular redox status. In addition to its defense function under oxidative stress, thioredoxin is now recognized for the wide spectrum activities in various biological processes including cell survival,
differentiation, apoptosis as well as immune-inflammatory response. Since gamma radiation can evoke oxidative stress conditions and activation of various intracellular signaling pathways associated with cellular defense mechanism, the present study focused on the function of thioredoxin as a radiation stress sensor to establish its role in radioprotection for cell survival against ROS-mediated cellular damage and in immunoregulation for defense against immune suppression induced by gamma
irradiation. Thus the present study is undertaken for (1) investigations on the function of thioredoxin during radiation stress response as a radiation sensor, (2) elucidation of radioprotection mechanism of thioredoxin for immune cells against radiation-induced apoptosis, and (3) establishment of the immune regulatory function and associated mechanism of thioredoxin action during radiation-induced immune suppression and inflammation. In particular, the molecular mechanism of Th1/Th2 counter-regulation by radiation and the signaling pathways was examined. The results of the study demonstrate that thioredoxin acts as a dual stress sensor for the induction of cell survival and apoptosis upon radiation stress depending on the target cell system. While thioredoxin promoted tumor cell death signal and conferred the sensitivity to both p53+/+ and p53-/- tumor cells for the radiation-induced apoptosis, it enhanced stress-mediated cell survival pathway of immune cells. In addition thioredoxin exerted immune-regulatory functions to recover from radiation-induced immune suppression by deviating immune cell differentiation pathway toward Th1, while inhibiting the radiation-induced Th2 cytokine induction. These data strongly suggest that thioredoxin modulates radiation stress response to overcome tumor cell resistance and to promote Th1 immune
function critical for anti-tumor defense through the immune cell survival and immune cell differentiation in favor of Th1 response, all of which make thioredoxin as an ideal target to be utilized for anti-tumor immune-protective therapy.

목차 Contents

• 표지 ... 1
• 제출문 ... 2
• 보고서 요약서 ... 3
• 요약문 ... 5
• SUMMARY ... 7
• CONTENTS ... 8
• 목차 ... 9
• 제1장 연구개발과제의 개요 ... 10
• 제 1절: 연구개발의 필요성 및 목적 ... 10
• 제2장 국내외 기술개발 현황 ... 13
• 제 1 절: 방사선 자극에 대한 thioredoxin의 세포방호효과에 대한 연구개발 현황 ... 13
• 제 2 절: 면역세포에서 방사선스트레스반응의 특성과 방사선의 면역조절효과 ... 14
• 제 3 절: Th1 면역반응 유도인자로서 Thioredoxin의 역할 ... 15
• 제3장 연구 개발수행 내용 및 결과 ... 16
• 제 1 절: Radiation stress sensor로서 thioredoxin의 기능:Thioredoxin sensitizses radiation stress in tumor cells(HCT116/p53wt) ... 16
• 제 2 절: 방사선자극에 대한 thioredoxin의 면역세포방호기전:Mechanism of thioredoxin action in protecting immune cells from apoptosisinduced by radiation stress ... 27
• 제 3 절 방사선유도 면역반응조절에서 thioredoxin의 작용 및 기전: Thioredoxin 의 Th1/Th2 반응 조절기능 및 작용기전 연구 ... 29
• 제4장 목표달성도 및 관련분야에의 기여도 ... 33
• 제 1 절 연구개발결과 및 목표달성도 ... 33
• 제 2 절 관련분야에의 기여도 ... 33
• 제5장 연구개발결과의 활용계획 ... 34
• 제 1 절: 연구개발결과요약 ... 34
• 제 2 절: 연구결과 활용계획 ... 35
• 제6장 참고문헌 ... 37