Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts.
Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts.
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PDK4 的下调对于人胎盘滋养细胞合体化过程中碳水化合物分解代谢的切换至关重要
DOI：
10.1038/s41598-017-09163-8
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发表时间：
2017-08-16
影响因子：
4.6
通讯作者：
Ying H
中科院分区：
文献类型：
--
作者：
Liu X;Zuo R;Bao Y;Qu X;Sun K;Ying H
丙酮酸脱氢酶激酶（PDK）是一种通过抑制丙酮酸脱氢酶复合物来引导碳流进入糖酵解的看门人。在胎盘滋养层细胞的合胞化过程中，ATP的产生和氧的消耗都增加，以满足合胞滋养层细胞增强的能量需求。我们推测PDK表达下调可能在合胞过程中从糖酵解到氧化磷酸化（OXPHOS）的转变中起着重要作用。通过使用原代人滋养层细胞，我们证明了PDK 4是人细胞滋养层细胞中主要的PDK亚型，并且其丰度在合胞化后大幅降低，这伴随着乳酸产生的减少和ATP产生的增加。PDK 4表达的敲低降低了乳酸产生并增加了ATP产生，而PDK 4的过表达增加了乳酸产生并减少了ATP产生，表明PDK 4的下调是合胞期间从糖酵解转变为OXPHOS的关键。此外，人绒毛膜促性腺激素（hCG）/cAMP/PKA通路被证明参与了合胞后PDK 4表达的下调。总之，我们的研究结果表明，PDK 4的下调是关键的代谢转变从糖酵解到OXPHOS合胞体化过程中，这可能是一个先决条件，适当的实施合胞体滋养层功能。
Pyruvate dehydrogenase kinase (PDK) is known as a gatekeeper directing the carbon flux into glycolysis via inhibition of the pyruvate dehydrogenase complex. During syncytialization of placental trophoblasts, both ATP production and oxygen consumption are increased to meet enhanced energetic demands by syntiotrophoblasts. We hypothesized that down-regulation of PDK expression may play a central role in the switch from glycolysis to oxidative phosphorylation (OXPHOS) during syncytialization. By using primary human trophoblasts, we demonstrated that PDK4 was the dominating PDK isoform in human cytotrophoblasts, and its abundance was substantially decreased upon syncytialization, which was accompanied by decreases in lactate production and increases in ATP production. Knock-down of PDK4 expression reduced lactate production and increased ATP production, while over-expression of PDK4 increased lactate production and decreased ATP production, indicating that down-regulation of PDK4 is key to the shift from glycolysis to OXPHOS during syncytialization. Moreover, human chorionic gonadotropin (hCG)/cAMP/PKA pathway was demonstrated to be involved in the down-regulation of PDK4 expression upon syncytialization. Taken together, our findings disclosed that down-regulation of PDK4 is critical for the metabolic shift from glycolysis to OXPHOS during syncytialization, which may be a prerequisite for the proper implementation of syncytiotrophoblast functions.
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影响因子：
46.9
作者：
Trapnell C;Williams BA;Pertea G;Mortazavi A;Kwan G;van Baren MJ;Salzberg SL;Wold BJ;Pachter L
通讯作者：
Pachter L
影响因子：
3.8
作者：
Weedon-Fekjraer, M. S.;Tasken, K.
通讯作者：
Tasken, K.
影响因子：
11.4
作者：
Zhang, Jin;Khvorostov, Ivan;Teitell, Michael A.
通讯作者：
Teitell, Michael A.
影响因子：
11.2
作者：
Doherty JR;Yang C;Scott KE;Cameron MD;Fallahi M;Li W;Hall MA;Amelio AL;Mishra JK;Li F;Tortosa M;Genau HM;Rounbehler RJ;Lu Y;Dang CV;Kumar KG;Butler AA;Bannister TD;Hooper AT;Unsal-Kacmaz K;Roush WR;Cleveland JL
通讯作者：
Cleveland JL
影响因子：
4.8
作者：
Korotchkina, LG;Patel, MS
通讯作者：
Patel, MS