GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration.
GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration.
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GLUT1过表达增强了葡萄糖代谢并促进新生儿心脏再生。
DOI：
10.1038/s41598-021-88159-x
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发表时间：
2021-04-21
影响因子：
4.6
通讯作者：
Nakano A
中科院分区：
文献类型：
--
作者：
Fajardo VM;Feng I;Chen BY;Perez-Ramirez CA;Shi B;Clark P;Tian R;Lien CL;Pellegrini M;Christofk H;Nakano H;Nakano A
哺乳动物心脏在出生后不久就将其主要代谢底物从葡萄糖转换为脂肪酸。这种代谢转换与心脏再生能力的丧失相吻合。然而，葡萄糖代谢是否调节心脏再生尚不清楚。在这里，我们报告说，葡萄糖代谢是新生哺乳动物心脏再生能力的决定因素。心脏特异性过表达的Glut 1，胚胎形式的组成型活性葡萄糖转运蛋白，导致增加葡萄糖摄取和伴随的积累糖原储存在出生后的心脏。冷冻损伤后，Glut 1转基因心脏表现出更高的再生能力，纤维化程度低于非转基因对照心脏。有趣的是，流式细胞术分析揭示了两种不同的心室心肌细胞群体：Tnnt 2-高和Tnnt 2-低心肌细胞，后者显示出显着更高的有丝分裂活性响应于高细胞内葡萄糖在Glut 1转基因心脏。代谢分析表明，Glut 1转基因心脏损伤后葡萄糖代谢产物（包括核苷酸）显著增加。核苷酸生物合成的抑制消除了心肌细胞内高葡萄糖水平的再生优势，表明葡萄糖通过供应核苷酸增强心肌细胞再生。我们的数据表明，葡萄糖代谢的增加促进新生小鼠心脏的心脏再生。
The mammalian heart switches its main metabolic substrate from glucose to fatty acids shortly after birth. This metabolic switch coincides with the loss of regenerative capacity in the heart. However, it is unknown whether glucose metabolism regulates heart regeneration. Here, we report that glucose metabolism is a determinant of regenerative capacity in the neonatal mammalian heart. Cardiac-specific overexpression of Glut1, the embryonic form of constitutively active glucose transporter, resulted in an increase in glucose uptake and concomitant accumulation of glycogen storage in postnatal heart. Upon cryoinjury, Glut1 transgenic hearts showed higher regenerative capacity with less fibrosis than non-transgenic control hearts. Interestingly, flow cytometry analysis revealed two distinct populations of ventricular cardiomyocytes: Tnnt2-high and Tnnt2-low cardiomyocytes, the latter of which showed significantly higher mitotic activity in response to high intracellular glucose in Glut1 transgenic hearts. Metabolic profiling shows that Glut1-transgenic hearts have a significant increase in the glucose metabolites including nucleotides upon injury. Inhibition of the nucleotide biosynthesis abrogated the regenerative advantage of high intra-cardiomyocyte glucose level, suggesting that the glucose enhances the cardiomyocyte regeneration through the supply of nucleotides. Our data suggest that the increase in glucose metabolism promotes cardiac regeneration in neonatal mouse heart.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
2.7
作者：
Darehzereshki, Ali;Rubin, Nicole;Gamba, Laurent;Kim, Jieun;Fraser, James;Huang, Ying;Billings, Joshua;Mohammadzadeh, Robabeh;Wood, John;Warburton, David;Kaartinen, Vesa;Lien, Ching-Ling
通讯作者：
Lien, Ching-Ling
DOI：
10.1126/science.1226603
发表时间：
2013-01-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Shyh-Chang N;Locasale JW;Lyssiotis CA;Zheng Y;Teo RY;Ratanasirintrawoot S;Zhang J;Onder T;Unternaehrer JJ;Zhu H;Asara JM;Daley GQ;Cantley LC
通讯作者：
Cantley LC
影响因子：
30.8
作者：
Patterson M;Barske L;Van Handel B;Rau CD;Gan P;Sharma A;Parikh S;Denholtz M;Huang Y;Yamaguchi Y;Shen H;Allayee H;Crump JG;Force TI;Lien CL;Makita T;Lusis AJ;Kumar SR;Sucov HM
通讯作者：
Sucov HM
DOI：
10.1073/pnas.1208863110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Porrello, Enzo R.;Mahmoud, Ahmed I.;Sadek, Hesham A.
通讯作者：
Sadek, Hesham A.