생명과학회지 (Journal of Life Science)

  • 제15권2호
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  • Pages.169-175
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  • 2005
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
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신경교 세포에서 resveratrol이 amyloid-β에 의해 유도되는 Cdk inhibitor p21 및 Bax 발현의 감소 효과

Effect of Resveratrol on the Induction of Cdk Inhibitor p21 and Pro-apoptotic Bax Expression by amyloid-β in Astroglioma C6 Cells

  • 김영애 (일본 부산의과약과대학 화한약연구소) ;
  • 임선영 (한국해양대학교 해양과학기술대학 해양과학부) ;
  • 고우신 (동의대학교 한의과대학 한의학과 및 한방바이오연구센터) ;
  • 최병태 (동의대학교 한의과대학 한의학과 및 한방바이오연구센터) ;
  • 이용태 (동의대학교 한의과대학 한의학과 및 한방바이오연구센터) ;
  • 이숙희 (부산대학교 생활환경대학 식품영양학과) ;
  • 박건영 (부산대학교 생활환경대학 식품영양학과) ;
  • 이원호 (부산대학교 자연과학대학 생물학과) ;
  • 최영현 (동의대학교 한의과대학 한의학과 및 한방바이오연구센터)
  • Kim Young Ae (Institute of Natural Medicine, Toyama Medical and Pharmaceutical University) ;
  • Lim Sun-Young (Division of Ocean Science, Korea Maritime University) ;
  • Ko Woo Shin (Department of Oriental Medicine, Dongeui University College of Oriental Medicine and Biomedical Research Center of Oriental Medicine) ;
  • Choi Byung Tae (Department of Oriental Medicine, Dongeui University College of Oriental Medicine and Biomedical Research Center of Oriental Medicine) ;
  • Lee Yong Tae (Department of Oriental Medicine, Dongeui University College of Oriental Medicine and Biomedical Research Center of Oriental Medicine) ;
  • Rhee Sook-Hee (Department of Food Science and Nutrition, Pusan National University) ;
  • Park Kun-Young (Department of Food Science and Nutrition, Pusan National University) ;
  • Lee Won-Ho (Department of Biology, Pusan National University) ;
  • Choi Yung Hyun (Department of Oriental Medicine, Dongeui University College of Oriental Medicine and Biomedical Research Center of Oriental Medicine)
  • 발행 : 2005.04.01
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초록

Resveratrol (3,4',5-trihydroxy-trans-stilbene)은 포도와 같은 식물에서 각종 감염균으로부터 자신의 몸을 보호하기 위하여 생성되는 물질인 phytoalexin의 일종으로 강력한 항산화작용, 암예방 효과 및 항암 작용을 포함한 각종 약리작용을 가진 것으로 보고 되어져 오고 있다. Alzheimer 환자의 뇌에 축적되어 뇌 신경세포를 죽이는 amyloid plaque의 주 성분은 $amyloid-\beta$의 축적에 의한 것인데, $amyloid-\beta$는 정상적인 단백질 신진대사 과정의 결과로 체내 모든 세포들로부터 생성되는 물질이다. 본 연구에서는 resveratrol의 세포독성 보호효과에 관한 효능을 검증하기 위하여 C6 신경교세포에서 $amyloid-\beta-peptide$ (fragment 31-35)에 의한 세포독성 및 세포성장 조절관련 주요 유전자들의 발현에 미치는 resveratrol의 영향을 조사하였다. $Amyloid-\beta$가 처리된 C6세포는 처리 농도의존적으로 증식이 억제되었으며, 형태적 변형도 유발 되었으나 resveratrol의 전처리에 의하여 효과적으로 차단되었다. RT-PCR 및 Western blot analysis에 의한 결과에서 $amyloid-\beta$ 처리에 의한 세포증식 억제는 종양억제유전자 p53 및 Cdk 억제제인 p21 (WAF1/CIP1) 발현이 증가되었다. 또한 apoptosis 유발에 매우 중요한 역할을 수행하는 Bax의 발현도 $amyloid-\beta$가 처리된 C6 세포에서 발현이 증가되었으나 apoptosis 유발억제에 관여하는 Bcl-2및 $Bcl-X_{L}$ 발현에는 큰 영향을 미치지 못하였다. 그러나 resveratrol이 전처리된 세포에서는 처리 농도 의존적으로 $amyloid-\beta$에 의해 유도되는 p53, p21 및 Bax의 발현이 정상수준으로 회복되었다.

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. $Amyloid-\beta$ deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease. In this study, we have explored the effects of resveratrol on $amyloid-\beta-peptide-mediated$ cytotoxicity in vitro and modulation of cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. Exposure of C6 cells to $Amyloid-\beta$ resulted in dose-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of $amyloid-\beta$ was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in $amyloid-\beta-treated$ C6 cells without alteration of anti-apoptotic Bcl-2 and $Bcl-X_L$ expression. However, pre-treatment of resveratrol significantly inhibited $amyloid-\beta-induced$ p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent. Our results demonstrate that resveratrol may enhance the protection against $amyloid-\beta-induced$ cytotoxicity by promoting the survival of glial cells.

키워드

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