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    Please use this identifier to cite or link to this item: http://ir.lib.ncu.edu.tw/handle/987654321/6302

    Title: 砷化物抑制Galectin-1基因之表現及機制之研究;The mechanism of arsenic inhibit galectin-1 gene expression.
    Authors: 潘雅芳;Ya-Fang Pan
    Contributors: 生命科學研究所
    Keywords: β-半乳糖苷蛋白;砷化物;galectin-1;arsenic
    Date: 2003-07-04
    Issue Date: 2009-09-22 10:17:14 (UTC+8)
    Publisher: 國立中央大學圖書館
    Abstract: 長期暴露在含有砷化物的環境之下,已知會造成肝臟的損傷與周邊血管疾病,如烏腳病及周邊神經病變等。此外長期暴露於砷化物中會提高皮膚癌,肺癌及膀胱癌發生的機會。而根據本實驗室之前的研究指出,三價砷在中國倉鼠卵巢細胞中會抑制一種特定蛋白-Galectin-1 (Gal-1) 的表現。而Gal-1蛋白是一種β-半乳糖苷蛋白,它能參與細胞貼附,增生與計劃性的細胞死亡。本論文進一步研究砷化物抑制Gal-1之表現及調控機制。 根據目前之研究結果指出三價砷對HFW,H1299,H460,KB,3T3等細胞內之Gal-1的量並無抑制現象。而在HaCaT與IRC細胞中Gal-1的表現量則會隨著砷化物處理的劑量而降低。砷化物在生物體中之代謝主要是經由甲基化之過程,而基因表現也與驅動子 (promoter) 之甲基化息息相關。因此我們進一步去探討在哺乳動物細胞中,砷化物是否會改變Gal-1基因之promoter區域的DNA methylation,而去抑制Gal-1基因之表現。我們將DNA利用二種對甲基化之敏感性不同的限制酶裁剪後,再以依照Gal-1基因之promoter序列所設計之primer,經PCR放大後,結果顯示在亞砷酸鈉所處理過的IRC細胞中,其Gal-1的promoter區域會有高度甲基化的情形。此外,將細胞前處理5-azadeoxycytidine (5-aza,一種甲基轉移酶的抑制劑),則可回復受亞砷酸鈉抑制的Gal-1基因mRNA及蛋白質表現。此一結果顯示,砷化物抑制Gal-1基因的表現是在transcription的層面,且與Gal-1基因promoter區段的過度甲基化有關。 Chronic exposure to arsenic has been associated with liver damage, peripheral vascular disease and peripheral neuropathy. Furthermore, exposure to excessive levels of arsenic has been correlated with an increased incidence of skin, lung and bladder cancers. The preliminary study in our laboratory showed that arsenite inhibits galectin-1 (gal-1) expression in CHOA cells. Gal-1 is a member of a growing family of animal ?-galactoside-binding proteins that are involved in the regulation of cell adhesion and immune function as well as proliferation and apoptosis. In this study, we further investigate the mechanism of arsenite-inhibited Gal-1 expression. The present results showed that arsenite has no effect on the expression of Gal-1 in HFW, H1299, H460, KB, 3T3 cells, however arsenite treatment results in dose-dependent inhibition of Gal-1 expression in HaCaT and IRC cells. Arsenite is metabolized in vivo by methylation and DNA methylation in promoter region involves in regulating gene expression. We propose that alteration of gal-1 DNA methylation of the promoter region by arsenic might contribute to the inhibition of gal-1 gene expression in mammalian cells. The DNA was first digested with methylation-sensitive/insensitive restriction enzymes, and PCR-amplified with primers derived from the promoter region of gal-1. The results showed that the promoter region of Gal-1 gene is hypermethylated in arsenite-treated IRC cells. Moreover, the arsenite-inhibited expression of Gal-1 mRNA and protein can be effectively restored by pre-treatment of cells with 5-azadeoxycytidine (5-aza, a methyltransferase inhibitor). The results suggested that arsenite inhibits Gal-1 expression in transcription level, and is mediated through DNA hypermethylation of the Gal-1 promoter region.
    Appears in Collections:[生命科學研究所 ] 博碩士論文

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