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Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish.
EMBO Reports ( IF 6.5 ) Pub Date : 2020-07-09 , DOI: 10.15252/embr.201949752
Ryuichi Fukuda 1, 2 , Rubén Marín-Juez 1, 2 , Hadil El-Sammak 1, 2 , Arica Beisaw 1, 2 , Radhan Ramadass 1, 2 , Carsten Kuenne 3 , Stefan Guenther 3, 4 , Anne Konzer 2, 5 , Aditya M Bhagwat 2, 5 , Johannes Graumann 2, 5 , Didier Yr Stainier 1, 2
Affiliation  

Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNA s encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss‐of‐function models for the metabolic regulators Pkma2 and peroxisome proliferator‐activated receptor gamma coactivator 1 alpha. Cardiomyocyte‐specific loss‐ and gain‐of‐function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC ) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK ‐PDC axis in cardiomyocyte behavior following cardiac injury.

中文翻译:


刺激糖酵解可促进成年斑马鱼受伤后心肌细胞增殖。



心脏代谢在产生足够的能量以维持心脏功能方面起着至关重要的作用。然而,代谢在心肌细胞再生不同方面的作用仍不清楚。通过研究成年斑马鱼心脏再生模型,我们首先发现编码调节葡萄糖和丙酮酸代谢的酶的 mRNA 水平增加,包括丙酮酸激酶 M1/2 (Pkm) 和丙酮酸脱氢酶激酶 (Pdks),特别是在与心脏相邻的组织中。受损区域。我们进一步发现,糖酵解受损会减少损伤后增殖的心肌细胞的数量。这些观察结果得到了使用代谢调节剂 Pkma2 和过氧化物酶体增殖物激活受体 γ 共激活剂 1 α 功能丧失模型的分析的支持。使用 Pdk3 以及丙酮酸脱氢酶复合物 (PDC) 的催化亚基对心肌细胞特异性的丙酮酸代谢功能丧失和功能获得进行操作,揭示了其在损伤后心肌细胞去分化和增殖中的重要性。此外,我们发现 PDK 活性可以调节培养的哺乳动物心肌细胞的细胞周期进程和突出活性。我们的研究结果揭示了心脏代谢和 PDK-PDC 轴在心脏损伤后心肌细胞行为中的新作用。
更新日期:2020-08-05
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