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| 題 名 | Overexpression of Glucose-6-phosphate Dehydrogenase (G6PD) in NIH 3T3 Cells Enhances Cell Proliferation=高量表現葡萄糖-六-磷酸去氫酶能促進NIH 3T3細胞的生長 |
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| 作 者 | 郭維英; 唐堂; | 書刊名 | Acta Zoologica Taiwanica |
| 卷 期 | 10:1 1999.01[民88.01] |
| 頁 次 | 頁15-24 |
| 分類號 | 381.8 |
| 關鍵詞 | 葡萄糖-六-磷酸去氫酶; 細胞生長; G6PD; NADPH; Cell proliferation; DHEA; |
| 語 文 | 英文(English) |
| 中文摘要 | 葡萄糖-六磷酸去氫�瞗]glucose-6-phosphate dehydrogenase, G6PD)是pentose phosphate pathway(PPP)第一個步驟的關鍵酵素,負責催化NADP+ 還原成NADPH,而NADPH則為細胞維持正常的氧化還原狀態(redox status)以及代謝活性氧化物(reactive oxygen species)所必需的還原力,過去的許多研究發現G6PD在細胞的抗氧化系統中扮演著重要的角色。此外,G6PD除了在抗氧化系統中提供NADPH的角色,也有報告指出G6PD的活性和細胞的生長能力有直接的相關,當細胞快速分裂(growth proliferation)時,G6PD的活性常有增高的情形。但是,G6PD的角色並不清楚,G6PD活性的增高有可能是促進生長(growth stimulation)上游的因,也有可能是下游的果。為了研究G6PD在調控細胞生長過程中所可能扮演的角色,我們利用轉染人類G6PD基因後獲得的G6PD-overexpressing NIH 3T3細胞,觀察它們的生長特性。我們的研究結果發現,大量表現G6PD的細胞H6(6倍)及H7(16倍),其生長能力會受到激發,細胞的生長速度都較只有轉殖質體的控制組細胞來得快,且細胞飽和密度(saturation density)也較高。如果用G6PD抑制劑來降低G6PD的活性,這個刺激生長的現象也會隨之降低。此外,G6PD-overexpressing cells其細胞型態會發生改變,呈現出已轉型細胞的樣子,而且也能在低血清(0.5%)的培養液中繼續分裂,這些都是轉型細胞的生長特質。我們的研究結果證明了G6PD活性的高低直接影響細胞生長的能力,而G6PD在細胞中的不正常活化,可能使細胞發生轉型。我們也提供了一個很好的模型可以用來研究G6PD刺激細胞生長的機制以及其他的參與因子。 |
| 英文摘要 | Glucose-6-phosphate dehydrogenase (G6PD) functions to catalyze the first step in the pen-tose phosphate pathway. The major physiological function of G6PD is to provide NADPH, which is required for reductive biosynthesis and for detoxification of free radicals and perox-ides in mature red blood cells. We previously showed that overexpression of human G6PD in NIH3T3 cells may alter the cellular redox status by enhancing intracellular NADPH and GSH levels (Kuo and Tang, 1998a). In this report, we provide evidence that an increase in G6PD activity is important for cell proliferation. To investigate the role of G6PD in cell growth, we stably transfected human G6PD cDNA into NIH 3T3 cells. Two G6PD-overex-pressing clones which had a 6-fold (H6) and a 16-fold (H7) increase, respectively, in their intracellular G6PD activity were compared with control cells transfected with a vector alone. Overexpression of G6PD promoted cell growth at both low (0.5%) and high (10%) serum conditions. When treated with dihydroepiandrosterone (DHEA), a potent G6PD inhibitor, stimulated cell growth in G6PD-overexpressing cells was significantly suppressed. Further-more, cells expressing high levels of human G6PD were able to grow to a higher cell density and proliferated in a low serum concentration, which are characteristicws of transformed phenotypes. These results show that G6PD activity is important not only in modulating intracellular redox status, but also in regulating cell proliferation. |
本系統中英文摘要資訊取自各篇刊載內容。