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악성 유방암 세포에서 celastrol 처리시 증가하는 mitochondria 칼슘 이온을 통한 paraptosis 세포 사멸 유도
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 최경숙 | - |
| dc.contributor.author | Lee, A Reum | - |
| dc.date.accessioned | 2019-10-21T07:21:45Z | - |
| dc.date.available | 2019-10-21T07:21:45Z | - |
| dc.date.issued | 2013-08 | - |
| dc.identifier.other | 15112 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/18255 | - |
| dc.description | 학위논문(석사)아주대학교 일반대학원 :의생명학과,2013. 8 | - |
| dc.description.tableofcontents | TABLE OF CONTENS ABSTRACT ------------------------------------------ⅰ TABLE OF CONTENT -------------------------------- ⅲ LIST OF FIGURES ------------------------------------ v I. INTRODUCTION ------------------------------------ 1 II. MATERIALS AND METHODS ------------------------ 6 A. Chemicals and antibodies ----------------------- 6 B. Cell culture ------------------------------------- 7 C. Measurement of cellular viability ----------------- 7 D. Western blotting --------------------------------- 7 E. mRFP-GFP-LC3 transfection --------------------- 8 F. Immunocytochemistry --------------------------- 8 G. Establishment of the stable cell lines in the fluorescence specifically mitochondria or the endoplasmic reticulum ----------------------- 9 H. Transmission electron microscopy --------------- 9 I. Measurement of ROS levels----------------------- 9 J. Measurement of mitochondrial superoxide anion levels ------------------------------------------ 10 K. Measurement of cytosolic and mitochondrial Ca2+ levels ----------------------------------------- 10 III. RESULTS ---------------------------------------- 11 1. Celastrol induces non-apoptotic cell death and partial apoptosis in human cancer cells----------------------11 2. Celastrol induces non-autophagic cell death in breast cancer cells ---------------------------- 16 3. Celastrol induces the swelling of mitochondria and the ER in breast cancer cells ------------------- 23 4. Release of Ca2+ from the ER via IP3 receptor and mitochondrial Ca2+ influx via uniporter are critical for celastrol-induced paraptosis ----------------- 37 5. ROS generation is also important for celastrol- induced paraptosis ---------------------------- 50 IV. DISCUSSION ------------------------------------ 60 V. REFERENCES ----------------------------------- 64 국문요약 ------------------------------------------- 77 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | 악성 유방암 세포에서 celastrol 처리시 증가하는 mitochondria 칼슘 이온을 통한 paraptosis 세포 사멸 유도 | - |
| dc.title.alternative | Celastrol induces paraptosis-like cell death via mitochondrial Ca2+ overload in breast cancer cells | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | A Reum Lee | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2013. 8 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 571072 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000015112 | - |
| dc.subject.keyword | Breast cancer | - |
| dc.subject.keyword | Celastrol | - |
| dc.subject.keyword | Paraptosis | - |
| dc.subject.keyword | ROS | - |
| dc.subject.keyword | Ca2+ | - |
| dc.description.alternativeAbstract | Various cancer cells are resistant to chemotherapeutic drugs-induced apoptosis. Thus, cancer cells that have acquired resistance to apoptosis need novel strategies for inducing non-apoptotic cell death. Paraptosis is a kind of non-apoptotic cell death and characterized by extensive vacuolization due to dilation of mitochondria and the endoplasmic reticulum (ER). However, the regulatory mechanisms that control paraptotic events are not yet fully understood. Recently, we found that celastrol, a triterpene extracted from the Chinese “Thunder of God Vine”, induced paraptosis accompanied by dilation of mitochondria and the ER in MDA-MB 435S and MCF-7 breast cancer cells. Inhibition of protein synthesis by cycloheximide blocked celastrol-induced vacuolation and subsequent cell death indicating that protein synthesis is required for this process. Generation of reactive oxygen species and mitochondrial Ca²⁺ overload was shown to act as a critical early signal in celastrol-induced paraptosis-like cell death contributing to the dilation of mitochondria/ER and subsequent paraptotic cell death. Inhibition of mitochondrial Ca2+ uniporter employing ruthenium red and IP₃ receptor employing 2-APB very effectively blocked celastrol-induced paraptosis-like cell death. Taken together, our results suggest that Ca²⁺ overload into the mitochondria via mitochondrial Ca2+ uniporter and IP3 receptor critically contribute to celastrol-induced paraptosis-like cell death. | - |
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