Chaperone DnaK and its Influence on Multiple Steps of Formation of Amyloid beta Structural Species Results in Differential Effects on Amyloid Beta Oligomer Formation and Concomitant Cytotoxicity
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- 발행기관
- 조선대학교 기초과학연구원 바로가기
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- 간행물
- 통합자연과학논문집(구 조선자연과학논문집) KCI 등재 바로가기
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- 통권
- 제6권 4호 (2013.12)바로가기
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- 페이지
- pp.220-233
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- 저자
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- 언어
- 영어(ENG)
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- URL
- https://www.earticle.net/Article/A210119
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원문정보
초록
- 영어
- Amyloid-β peptide (Aβ), implicated in Alzheimer's disease, associates into the fibrils that deposit in senile plaque. The 39~43 amino acid long peptide assemble into various species which could be regulated by chaperone molecules. Despite extensive progress, the results are conflicting; for example, both reduction and enhancement of Aβ cytotoxicity by chaperone have been reported. And the relationship of Aβ structural species with chaperone, and further its implication in cytotoxicity remain to be elucidated. To address this question and to understand the underlying mechanism(s), in this study, the effect of a chaperone molecule, DnaK, on Aβ structure and its effect on cytotoxicity were investigated under several different conditions. A significant amount of oligomeric species of Aβ that is believed to be more toxic among Aβ structures was accumulated at 0.01~0.1 ratio of DnaK/abeta42, while such accumulation was not observed with higher ratio, where the oligomers appeared in the form of complexes with the chaperone molecules. Importantly, accumulation of these Aβ oligomers exerted enhanced toxicity concomitantly and, in contrast, cytoprotection was observed at excess molar of DnaK. In all conditions, fibrillar forms were markedly inhibited. Further, fibrillization kinetics indicated that DnaK might affect on nucleation step, while circular dichroism spectroscopy demonstrated that DnaK delayed overall β- sheet formation. Taken together, results indicate that the chaperone influences Aβ structural transition from oligomer to fibrillar structures as well as from monomer to oligomer with variable rates, and as results, it decreased or increased the amount of Aβ oligomer as well as the cytotoxicity.
목차
Abstract
1. Introduction
2. Experimental Section
2.1. Materials
2.2. Purification of Protein
2.3. Peptide of Preparation
2.4. SDS-PAGE and Immunoblotting
2.5. Dot-Blot Assay
2.6. Thioflavin T Binding Assay
2.7. Turbidity Assay
2.8. Fibril Formation and Fiber Extension Assay
2.9. CD Spectroscopy
2.10. Electron Microscopy
2.11. Cell Culture and Toxicity Assay
2.12. Caspase-3 Activity Assay
3. Results and Discussion
3.1. Dnak Regulates Accumulation of Aβ42 Oligomeric Species
3.2. Dnak Affects Aβ Fibril Formation and Elongation
3.3. Effects of DnaK on Secondary Structure of Aβ
3.3. DnaK Enhances or Suppresses Aβ42 Mediated Toxicity
3.4. Discussion
4. Conclusions
References
키워드
Aβ Intermediate Species Chaperones ADDLs Protofibrils Fibrils Dnak/Aβ Ratio저자
간행물 정보
발행기관
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- 발행기관명
- 조선대학교 기초과학연구원 [The Natural Science Research Institute of Chosun]
- 설립연도
- 2008
- 분야
- 자연과학>자연과학일반
- 소개
- 본 연구원은 기초과학을 진흥하기 위한 연구·교육 및 그 보급을 목적으로 한다. 이 목적을 달성하기 위하여 다음 각 호의 사업을 수행한다. 1. 기초과학 제 분야에 관한 조사와 연구 2. 기초과학에 관한 학술행사(학술대회, 학술세미나, 심포지엄, 초청강연회 등) 개최 3. 학문후속세대 및 일반인을 위한 기초과학 교육 4. 기관지『조선자연과학논문지』 발간 5. 『자연과학연구총서』, 『자연과학번역총서』 등 단행본 발간 6. 기타 본 연구원의 목적과 관련된 사업
간행물
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- 간행물명
- 통합자연과학논문집(구 조선자연과학논문집) [Journal of Integrative Natural Science]
- 간기
- 계간
- pISSN
- 2005-1042
- 수록기간
- 2008~2025
- 등재여부
- KCI 등재
- 십진분류
- KDC 405 DDC 505
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