Balatskyi Volodymyr V, Palchevska Oksana L, Bortnichuk Lina, Gan Ana-Maria, Myronova Anna, Macewicz Larysa L, Navrulin Viktor O, Tumanovska Lesya V, Olichwier Adam, Dobrzyn Pawel, Piven Oksana O
Department of Human Genetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Akademika Zabolotnogo Street, 03680 Kyiv, Ukraine.
Laboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland.
Life (Basel). 2020 Dec 17;10(12):357. doi: 10.3390/life10120357.
The role of canonical Wnt signaling in metabolic regulation and development of physiological cardiac hypertrophy remains largely unknown. To explore the function of β-catenin in the regulation of cardiac metabolism and physiological cardiac hypertrophy development, we used mice heterozygous for cardiac-specific knockout that were subjected to a swimming training model. haploinsufficient mice subjected to endurance training displayed a decreased β-catenin transcriptional activity, attenuated cardiomyocytes hypertrophic growth, and enhanced activation of AMP-activated protein kinase (AMPK), phosphoinositide-3-kinase-Akt (Pi3K-Akt), and mitogen-activated protein kinase/extracellular signal-regulated kinases 1/2 (MAPK/Erk1/2) signaling pathways compared to trained wild type mice. We further observed an increased level of proteins involved in glucose aerobic metabolism and β-oxidation along with perturbed activity of mitochondrial oxidative phosphorylation complexes (OXPHOS) in trained haploinsufficient mice. Taken together, Wnt/β-catenin signaling appears to govern metabolic regulatory programs, sustaining metabolic plasticity in adult hearts during the adaptation to endurance training.
经典Wnt信号通路在代谢调节及生理性心肌肥大发展过程中的作用在很大程度上仍不清楚。为了探究β-连环蛋白在心脏代谢调节及生理性心肌肥大发展中的功能，我们使用了心脏特异性敲除杂合子小鼠，并使其接受游泳训练模型。与经过训练的野生型小鼠相比，接受耐力训练的单倍剂量不足小鼠表现出β-连环蛋白转录活性降低、心肌细胞肥大生长减弱，以及AMP激活的蛋白激酶（AMPK）、磷酸肌醇-3-激酶-蛋白激酶B（Pi3K-Akt）和丝裂原活化蛋白激酶/细胞外信号调节激酶1/2（MAPK/Erk1/2）信号通路的激活增强。我们进一步观察到，在经过训练的单倍剂量不足小鼠中，参与葡萄糖有氧代谢和β-氧化的蛋白质水平升高，同时线粒体氧化磷酸化复合物（OXPHOS）的活性受到干扰。综上所述，Wnt/β-连环蛋白信号通路似乎在调控代谢调节程序，在成年心脏适应耐力训练的过程中维持代谢可塑性。
