碩士 / 國立臺灣海洋大學 / 食品科學系 / 99 / This study aims to investigate the effects of food component on cell migration in human hepatoma cells. Previous studies revealed that mitochondrial dysfunction-induced amphiregulin (AR) upregulation mediates cell migration and chemoresistance in HepG2 cells. Moreover, mitochondrial dysfunction induced intracellular hydrogen peroxide overproduction and calcium mobilization may modulate AR induction in this setting. In this study, the mitochondrial dysfunction was defined as the dysfunction of mitochondrial respiratory chain, such as treatment with the inhititor of ATPase (oligomycin). Firstly, this study investigated the roles of Tumor necrosis factor-alpha converting enzyme (TACE) activation and Interlukin-8 (IL-8) induction in mitochondrial dysfunction-induced AR secretion. Subsequently, this study investigated the effects and mechanisms of food component on mitochondrial dysfunction-induced cell migration in human hepatoma cells.
This study revealed that the activities of TACE were activated by mitochondrial dysfunction in HepG2 cells, in time-dependent manner. Besides, oligomycin-induced TACE activation of HepG2 cells was attenuated by IL-8 and IL-8RA-specific RNA interferences. Furthermore, mitochondrial dysfunction upregulated IL-8 induction and secretion in various types of human hepatoma cell lines, including poorly differentiated cells (HA22T/VGH and SK-Hep-1), and well-differentiated cells (HepG2, Hep3B, and HuH7). Meanwhile, mitochondrial dysfunction-induced IL-8 overexpression was abolished by IL-8 and AR neutralizing antibody, respectively. Together, these findings suggest that mitochondrial dysfunction-induced IL-8 induction, as well as AR upregulation mediates cell migration via TACE activation.
On the other hand, pretreatment of hydrolyzed Chlorella sorokiniana decreased mitochondrial dysfunction-induced hydrogen peroxide (H2O2) production in a concentration-dependent manner. Additionally, hydrolyzed Chlorella sorokiniana concentration-dependently suppressed AR release, but not IL-8 secretion and TACE activation, in HepG2 cells. These findings suggest that hydrolyzed Chlorella sorokiniana may inhibit cell migration by improvement of ROS scavenging and attenuation of AR release in human hepatoma cells.
| Identifer | oai:union.ndltd.org:TW/099NTOU5253078 |
| Date | January 2011 |
| Creators | Chun-Huan Chou, 周君奐 |
| Contributors | Chun-Ju Chang, 張君如 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 105 |
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