近日,，研究者發(fā)現(xiàn)處于增殖期的非洲爪蟾的視網(wǎng)膜細(xì)胞采用的是有氧糖酵解而不是氧化磷酸化,。表明以往Warburg effect只發(fā)生在腫瘤細(xì)胞中的認(rèn)識(shí)是片面的，Warburg effect或許普遍存在于增殖代謝中,。相關(guān)論文發(fā)表在近期的Nature Cell Biology上,。
瓦氏效應(yīng)(Warburg effect),，指奧托·海因里希·瓦爾堡(Otto Heinrich Warburg)所提出的理論,，認(rèn)為癌細(xì)胞的生長速度遠(yuǎn)大于正常細(xì)胞的原因來自于能量的來源差別,。癌細(xì)胞會(huì)偏向使用糖酵解作用取代一般正常細(xì)胞的氧化磷酸化。
Agathocleous等人發(fā)現(xiàn)，處于發(fā)育期的視網(wǎng)膜增殖的祖細(xì)胞通過糖酵解將葡萄糖轉(zhuǎn)化為乳酸,，即使有氧也是如此,。若用糖原磷酸化酶抑制劑（glycogen phosphorylase inhibitor,GPI）處理胚胎，視網(wǎng)膜祖細(xì)胞仍然依賴糖酵解進(jìn)行增殖,。只有分化為終末分化的視網(wǎng)膜細(xì)胞才依賴氧化磷酸化供能。
通常認(rèn)為胞外的葡萄糖對(duì)于細(xì)胞的增殖是必須的,，但是此項(xiàng)研究表明在某些增殖細(xì)胞中糖原可作為葡萄糖產(chǎn)生的源泉,。糖酵解對(duì)于細(xì)胞增殖的作用不是產(chǎn)生更多的ATP，而是生物合成,，例如產(chǎn)生所有核苷酸合成的前體--核糖-5-磷酸,。
由于整體動(dòng)物水平代謝跟蹤方法（whole-animal metabolic tracing methods）的廣泛使用，闡明體內(nèi)組織的代謝方式變得簡單,。而我們首先應(yīng)該明白的是,，在同一種組織中增殖和非增殖細(xì)胞的代謝方式可能是完全不同的。（生物谷Bioon.com）
doi:10.1038/ncb2554
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Seeing the Warburg effect in the developing retina
Brian P. Fiske1 & Matthew G. Vander Heiden1
During development, instead of using extracellular glucose, Xenopus retina cells rely on intracellular nutrient stores, including glycogen1. Agathocleous et al. now demonstrate in vivo that proliferating progenitor cells of the developing retina rely on aerobic glycolysis (rather than on oxidative phosphorylation), which converts glucose to lactate, to support their metabolic needs2. This occurs even in the presence of oxygen, despite the fact that, when oxygen is available, oxidative phosphorylation allows more ATP to be produced per mole of glucose than glycolysis alone (Fig. 1). Interestingly, this preference for aerobic glycolysis is regulated by glycogen-phosphorylase-mediated glycogen metabolism. Even when progenitor cells are forced to utilize oxidative phosphorylation to produce ATP, by treating developing embryos with a glycogen phosphorylase inhibitor (GPI)3, they continue to depend on glycolytic flux for proliferation and survival. Only after terminal differentiation to non-proliferating retinal cells do the cells switch to oxidative phosphorylation. This work demonstrates that normal proliferating embryonic tissues use aerobic glycolysis even when relying on intracellular nutrient stores.
