Glycolysis in preimplantation development is partially controlled by the Warburg Effect
Glycolysis in preimplantation development is partially controlled by the Warburg Effect
复制标题
DOI：
10.1002/mrd.22017
复制
发表时间：
2012-04-01
影响因子：
2.5
通讯作者：
Prather, Randall S.
中科院分区：
文献类型：
--
作者：
Redel, Bethany K.;Brown, Alana N.;Prather, Randall S.
传统上，植入前胚胎的葡萄糖代谢是从体细胞的角度来观察的。在这里，我们展示了早期胚胎中的基因表达类似于快速分裂的癌细胞。在体外培养的猪囊胚中进行了深度测序，发现表达了两个与癌细胞代谢有关的基因变体(HK2和PKM2的M2变体)。在低氧或高氧(空气中5%二氧化碳、5%氧气、90%氮气与5%二氧化碳)培养的额外胚胎中，监测发育并量化基因表达。两种气氛下的囊胚期发育情况相似，不同之处在于低氧比高氧能产生更多的总核团和内细胞核。在筛选出的15个与糖代谢相关的候选基因中，只有TALDO1和PDK1在低氧环境中表达增加。用于解释低氧分压下糖酵解的一个范例是Warburg效应(WE)。我们预测，HK2和PKM2 M2的表达都会导致TCA循环中葡萄糖代谢的放缓，从而迫使糖酵解的产物通过戊糖磷酸途径代谢成乳酸。这种系统的充电显然对早期胚胎是如此重要，以至于存在多余的机制，即胎儿形式的PKM2和高水平的PDK1。在这里，我们建立了框架，使用WE来描述植入前发育过程中的葡萄糖代谢和能量产生。摩尔。是Reprod。戴夫。2012年，79：262271。(C)2011年威利期刊公司。
Glucose metabolism in preimplantation embryos has traditionally been viewed from a somatic cell viewpoint. Here, we show that gene expression in early embryos is similar to rapidly dividing cancer cells. In vitro-produced pig blastocysts were subjected to deep-sequencing, and were found to express two gene variants that have been ascribed importance to cancer cell metabolism (HK2 and the M2 variant of PKM2). Development was monitored and gene expression was quantified in additional embryos cultured in low or high O2 (5% CO2, 5% O2, 90% N2 vs. 5% CO2 in air). Development to the blastocyst stage in the two atmospheres was similar, except low O2 resulted in more total and inner cell mass nuclei than high O2. Of the 15 candidate genes selected that are involved in glucose metabolism, only TALDO1 and PDK1 were increased in the low O2 environment. One paradigm that has been used to explain glycolysis under low oxygen tension is the Warburg Effect (WE). The WE predicts that expression of both HK2 and PKM2 M2 results in a slowing of glucose metabolism through the TCA cycle, thereby forcing the products of glycolysis to be metabolized through the pentose phosphate pathway and to lactic acid. This charging of the system is apparently so important to the early embryo that redundant mechanisms are present, that is, a fetal form of PKM2 and high levels of PDK1. Here, we set the framework for using the WE to describe glucose metabolism and energy production during preimplantation development. Mol. Reprod. Dev. 79: 262271, 2012. (C) 2011 Wiley Periodicals, Inc.