Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/36244
標題: 人類6-磷酸葡萄糖異構酵素與鳥糞嘌呤核苷三磷酸鹽結合對生理影響之探討
Investigating the Biological Effects of the Interaction between GTP and Human Phosphoglucose Isomerase
作者: 劉霓蓉
Liu, Ni-Rung
關鍵字: human phosphoglucose isomerase;人類6-磷酸葡萄糖異構酵素
出版社: 生物科技學研究所
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摘要: 
6-磷酸葡萄糖異構酵素 ( phosphoglucose isomerase, PGI) 是一個廣泛存在於各種細胞內的多功能性蛋白質,在醣解作用與醣質新生作用代謝路徑中負責催化6-磷酸葡萄糖與6-磷酸果糖間可逆性的轉換。在細胞外,PGI也是一種腫瘤自泌移動因子 (autocrine motility factor, AMF) 能促使腫瘤細胞移動;此外也是具有支持脊髓及感覺神經元生長能力的神經白素以及調節單核細胞 (monocytic cells) 成熟的免疫細胞成熟因子。前人研究發現腫瘤細胞會過度表達AMF,許多惡性腫瘤 (如腸胃道、腎、乳、結腸直腸及肺癌) 病患血液或尿液中的AMF濃度會提升,因此被視為一種腫瘤標記分子。本實驗室先前研究中發現human PGI (簡稱hPGI) 具有結合GTP的能力。為了探討hPGI與GTP結合的生理意義,本研究將hPGI與GTP分別或同時加入肺癌細胞株A549與胚胎腎細胞株HEK293之培養液中,在48小時後觀察細胞形態並以MTT及WST-1 assays測定細胞的存活率。初步試驗結果得知當GTP濃度高於50 uM會抑制細胞的生長,而hPGI (0.16 uM、0.79 uM) 會提高細胞存活率約10%-20%,然而同時處理hPGI與濃度25 uM、50 uM的GTP會造成細胞存活數的下降。之後利用螢光染劑Hoechst 33342進行細胞核染色觀測核染色質形態變化,發現A549細胞在hPGI與GTP共同處理下,細胞核的染色質有濃縮聚集的現象,以上結果暗示hPGI與GTP的結合可能引發細胞凋亡。本研究也利用小室遷移試驗探討細胞外hPGI與GTP共同存在下對於人類肝癌細胞HepG2與老鼠大腸癌細胞CT-26的移動影響。試驗結果發現,在hPGI與GTP共同處理下會抑制hPGI本身促進HepG2與CT-26細胞之移行能力,與單獨加入hPGI之組別相比,HepG2細胞的移動比例降低90%,而CT-26細胞的移動比例降低了50%,以上結果暗示當hPGI與GTP共存時會透過某種機制而抑制hPGI的促細胞移動能力。

Phosphoglucose isomerase (PGI) is a multifunctional protein ubiquitously expressed in cell. Inside the cells, it catalyzes the interconversion of glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P), the second step of the glycolytic pathway. Outside the cells, PGI moonlights as an autocrine motility factor (AMF) involved in cancer metastasis development. PGI can also function as a neuroleukin that facilitates survival and growth of embryonic spinal and sensory neurons; a maturation factor mediating the differentiation of myeloid leukemic HL-60 cells to terminal monocytic cells. AMF/PGI is secreted by tumor cells to detectable levels in both serum and urine and thus has been used as a prognostic marker of cancer progression. Previous study discovered that human PGI (hPGI) could bind to GTP; however, the physiological significance of interaction is unknown. Thus, to realize the effects of the interaction between hPGI and GTP on cell proliferation, hPGI and/or GTP was added into the culture media of A549 and HEK293 cell lines. Cell viability was quantified after 48 hours incubation by using MTT and WST-1 assays. The data showed that GTP decreased cell proliferation when its concentration was more than 50 uM, whereas hPGI (0.16 uM、0.79 uM) enhanced proliferation about 10%-20%. However, treatment of hPGI with low GTP concentrations (i.e. 25 uM and 50 uM) caused a decline in the number of cells. By Hoechst 33342 staining used to observe nuclear morphological changes, A549 cells exhibited condensed chromatin gathering with the co-treatment of hPGI and GTP suggesting the binding of hPGI to GTP may induce apoptosis of A549 cells. To study the effects of hPGI and GTP on cell motility, the migration rates of HepG2 and CT-26 cell lines were assayed by transwell. hPGI and GTP inhibited the cell motility-stimulating activity of AMF/PGI. Compared to the cells with hPGI, co-treatment of hPGI and GTP reduced the migration rate by 90% and 50% on HepG2 cells and CT-26 cells respectively. These results implicating there is an unknown mechanism of inhibition of the cell locomotion by hPGI-GTP.
URI: http://hdl.handle.net/11455/36244
其他識別: U0005-1708201018215400
Appears in Collections:生物科技學研究所

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