颠倒
重编程
磷酸化
细胞生物学
p38丝裂原活化蛋白激酶
再生(生物学)
MAPK/ERK通路
化学
生物
生物化学
细胞
工程类
汽车工程
作者
Luxun Tang,Yu Shi,Qiao Liao,Feng Wang,Hao Wu,Hongmei Ren,Xuemei Wang,Wenbin Fu,Jialing Shou,Wei Eric Wang,Pedro A. José,Yongjian Yang,Ceng Bi Zeng
标识
DOI:10.1016/j.apsb.2024.11.001
摘要
The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.
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