Glycolytic network restructuring integral to the energetics of embryonic stem cell cardiac differentiation.
Glycolytic network restructuring integral to the energetics of embryonic stem cell cardiac differentiation.
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DOI：
10.1016/j.yjmcc.2009.12.014
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发表时间：
2010-04
影响因子：
5
通讯作者：
Dzeja PP
中科院分区：
文献类型：
--
作者：
Chung S;Arrell DK;Faustino RS;Terzic A;Dzeja PP
对胚胎干细胞心脏分化背后的生物能量特征的解码揭示了代谢基础结构的强制性转变，其中线粒体网络扩张突出，以及从糖酵解到氧化磷酸化的独特转变。在这里，我们证明，尽管减少总糖酵解能力，干细胞心脏发生从事一个显着的转录组，蛋白质组，以及酶和拓扑重排的近端，中间和远端模块的糖酵解途径。糖酵解重组表现为己糖激酶（Hk）亚型从Hk-2转变为心脏Hk-1，细胞内和肌原纤维间定位映射线粒体网络排列。此外，心肌特异性烯醇化酶3、磷酸果糖激酶、磷酸葡萄糖变位酶的上调和甘油醛3-磷酸脱氢酶（GAPDH）磷酸转移活性的显著增加，沿着GAPDH和磷酸甘油酸激酶的明显翻译后修饰，与胚胎干细胞来源相比，衍生的心肌细胞都是独特的。乳酸脱氢酶（LDH）亚型向LDH-2和LDH-3进化，含有更高比例的心脏特异性亚基，丙酮酸脱氢酶亚型在E1α和E1β之间重排，有利于线粒体中底物氧化的转变。同时，胎儿丙酮酸激酶亚型M2，醛缩酶3和转酮醇酶，分流的糖酵解与磷酸戊糖途径，转录水平降低。总的来说，糖酵解途径模块的变化表明积极的重新部署，这将有助于扩大线粒体网络与ATP利用位点的连接。因此，描绘的糖酵解磷酸转移网络的发育动力学是不可或缺的干细胞心脏发生的细胞能量基础设施的重塑。
Decoding of the bioenergetic signature underlying embryonic stem cell cardiac differentiation has revealed a mandatory transformation of the metabolic infrastructure with prominent mitochondrial network expansion, and a distinctive switch from glycolysis to oxidative phosphorylation. Here, we demonstrate that despite reduction in total glycolytic capacity, stem cell cardiogenesis engages a significant transcriptome, proteome, as well as enzymatic and topological rearrangement in the proximal, medial, and distal modules of the glycolytic pathway. Glycolytic restructuring was manifested by a shift in hexokinase (Hk) isoforms from Hk-2 to cardiac Hk-1, with intracellular and intermyofibrillar localization mapping mitochondrial network arrangement. Moreover, upregulation of cardiac specific enolase 3, phosphofructokinase, phosphoglucomutase and a marked increase in glyceraldehyde 3-phosphate dehydrogenase (GAPDH) phosphotransfer activity, along with apparent post-translational modifications of GAPDH and phosphoglycerate kinase, were all distinctive for derived cardiomyocytes compared to the embryonic stem cell source. Lactate dehydrogenase (LDH) isoforms evolved towards LDH-2 and LDH-3, containing higher proportions of heart-specific subunits, and pyruvate dehydrogenase isoforms rearranged between E1α and E1β, transitions favorable for substrate oxidation in mitochondria. Concomitantly, transcript levels of fetal pyruvate kinase isoform M2, aldolase 3 and transketolase, which shunt the glycolytic with pentose phosphate pathways, were reduced. Collectively, changes in glycolytic pathway modules indicate active redeployment which would facilitate connectivity of the expanding mitochondrial network with ATP utilization sites. Thus, the delineated developmental dynamics of the glycolytic phosphotransfer network is integral to the remodeling of cellular energetic infrastructure underlying stem cell cardiogenesis.
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DOI：
10.1084/jem.20061916
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Behfar A;Perez-Terzic C;Faustino RS;Arrell DK;Hodgson DM;Yamada S;Puceat M;Niederländer N;Alekseev AE;Zingman LV;Terzic A
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影响因子：
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作者：
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Terzic, Andre
DOI：
10.1073/pnas.0809144106
发表时间：
2009-01-27
影响因子：
11.1
作者：
Hsu, Hwei-Jan;Drummond-Barbosa, Daniela
通讯作者：
Drummond-Barbosa, Daniela
影响因子：
2.3
作者：
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通讯作者：
Branch, S
影响因子：
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作者：
de Groof, AJC;Oerlemans, FTJJ;Wieringa, B
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