葡萄糖六磷酸鹽去氫酶在斑馬魚早期發育的影響

葡萄糖-6-磷酸去氫酶（Glucose-6-phosphate dehydrogenase，G6PD），主要調控五碳糖磷酸代謝途徑（pentose-phosphate pathway），使得葡萄糖-6-磷酸（Glucose-6-phosphate）轉換成6-磷酸葡萄糖酸內酯（6-phosphogluconolactone），同時伴隨著產生還原態的菸草醯胺腺嘌呤二核苷酸磷酸鹽（Nicotinamide adenine dinucleotide phosphate，NADPH），對於細胞而言，提供了還原的能量，使得細胞得以消除細胞內的過氧化物，避免過氧化物過度的累積，造成細胞的損傷或凋亡。在臨床上，主要是研究G6PD缺乏時造成的影響，像是蠶豆症。近年還有研究發現此酵素和癌症、心臟血管病症及中風有關，但是對於此酵素對於胚胎發育和生長的調控研究較少，所以，在研究中利用斑馬魚動物模式，在胚胎中注射反義股核苷酸（Morpholino），阻斷G6PD的表現，減少斑馬魚胚胎中G6PD表現，結果發現比起正常魚體，G6PD缺乏的斑馬魚的體型有明顯變小，卵黃囊腫大和微心腔腫大的情形。再者，分析活性氧化物（ROS）的堆積和氧化壓力相關基因（FOXM1和NOX5）都有增加的現象，由這些結果可以證明G6PD在發育中扮演著重要的角色，提供胚胎清除活性氧化物的能力，使胚胎能夠正常發育生長。

關鍵字

葡萄糖-6-磷酸去氫酶活性氧化物；斑馬魚；反義股核苷酸

並列摘要

Glucose-6-phosphate dehydrogenase (G6PD) is the rate limiting enzyme in pentose-phosphate pathway. G6PD catalyzes glucose-6-phosphate to 6-phosphogluconolactone and concomitantly produced Nicotinamide adenine dinucleotide phosphate (NADPH). In cells, the NADPH serves as the reduced energy to eliminate the reactive oxygen species (ROS) and oxidative damage. In clinical, recent studies reveal the G6PD deficiency is associated with cancer, cardiovascular disease and stroke. Due to G6PD deficiency induced embryonic lethality, little is known about the role of G6PD during early embryonic development and organism level. In this study, zebrafish was used as an animal model. By injecting G6PD morpholino (MO) to the embryo, the G6PD-knockdown zebrafish was established. In phenotype, G6PD-knockdown zebrafish showed smaller size, enlarged yolk, and enlarged cardiac edema. Furthermore, increasedROS accumulation and up-regulated oxidative stress associated gene expression were detected in G6PD-knockdown zebrafish. These results suggest that G6PD plays an important role during zebrafish early embryonic development.

並列關鍵字

Glucose-6-phosphate dehydrogenase ； reactive oxygen species ； zebrafish ； morpholino

參考文獻

1. Wood, T. The pentose phosphate pathway (Academic Press, Orlando, 1985).

2. Wamelink, M.M., Struys, E.A. & Jakobs, C. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis 31, 703-17 (2008).

4. Adam, A. Linkage between deficiency of glucose-6-phosphate dehydrogenase and colour-blindness. Nature 189, 686 (1961).

5. Takizawa, T., Huang, I.Y., Ikuta, T. & Yoshida, A. Human glucose-6-phosphate dehydrogenase: primary structure and cDNA cloning. Proc Natl Acad Sci U S A 83, 4157-61 (1986).

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葡萄糖六磷酸鹽去氫酶在斑馬魚早期發育的影響

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