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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42522
標題: | 細胞膜修補誘發與HDAC6無關的自噬作用與
蛋白質聚集體形成 Membrane repair induced HDAC6-independent autophagy and aggresome formation |
作者: | Yu-Ting Weng 翁于婷 |
指導教授: | 張震東(Geen-Dong Chang) |
關鍵字: | 自噬作用,細胞膜修補,HDAC6,ubiquitin, autophagy,membrane repair,HDAC6,ubiquitin, |
出版年 : | 2009 |
學位: | 碩士 |
摘要: | 細胞因為機械壓力或外力所造成短細胞膜傷害,在細胞膜受傷後,細胞內會接觸到細胞外相對氧化的環境,造成胞內蛋白質被氧化形成蛋白質聚集(protein aggregates)。此外,細胞外Ca2+大量進入細胞內,促進液泡融合(vesicles fusion)或胞吐作用(exocytosis)於損傷處形成膜狀區塊,防止細胞內物質持續溢出細胞。之後細胞會進行胞吞作用(endocytosis)產生內吞體(endosome)移除細胞膜上的修補區域,而促進細胞膜的組成復原。目前還沒有人提出細胞膜傷害後,蛋白質聚集、膜狀區塊以及內吞體是如何被清除。
本篇論文中,利用磁珠滾動的方式大規模傷害細胞的細胞膜後,發現在滾珠後四小時會誘發自噬作用。若3-methyladenine (3-MA)抑制自噬作用則會使滾珠後細胞的存活率下降,顯示自噬作用可輔助細胞膜修補來增加細胞的存活率。此外,我們發現HDAC6不參與此類的自噬作用,而且此類的自噬作用並不幫助清除polyubiquitined proteins。由於蛋白質聚集、膜狀區塊以及內吞體沒有polyubiquitination,應該不是透過ubiquitin的途徑來降解,而且它們的分子量都很大,因此細胞滾珠後誘發的自噬作用可能可以幫助清除蛋白質聚集、膜狀區塊以及內吞體的機制。 Transient plasma membrane disruptions commonly occur in cells that experience mechanical stress or external force. From what we have known, disruption of the plasma membrane would lead to the exposure of the cell interior to the external oxidizing environment and change the oxidation state of proteins in cells. These oxidized proteins would become extensively aggregated or cross-linked and attach to the disrupted plasma membrane. Furthermore, extracellular Ca2+ would enter cells, promoting vesicle fusion and exocytosis to form membrane patches that prevent cell contents from spilling out of cells. Afterward, damaged cells proceed to endocytosis and the formation of endosomes that promote the replacement of wound areas in plasma membrane. Protein aggregates, membrane patches, and endosomes that occur during plasma membrane disruption might cause cell stress. At present, it remains unclear how protein aggregates, membrane patches, and endosomes are eliminated in cells after membrane damage. Here, the results suggest that membrane damage at 4 hour after magnetic beads rolling is able to induce autophagy. By blocking autophagy with 3-methyladenine (3-MA), cell viability decreased after beads rolling. These results imply that autophagy participates in membrane repair. Moreover, we found that polyubiquitination and HDAC6 were not involved in the autophagic process following membrane damage and repair. Since ubiquitination plays a minimal role, autophagy, an alternative pathway caused by beads rolling, might help to eliminate protein aggregates, membrane patches and endosomes. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42522 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科學研究所 |
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