Department of Anatomy, College of Basic Medicine, Guilin Medical University, Guilin, China.
Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, China.
PLoS One. 2024 Jul 22;19(7):e0307696. doi: 10.1371/journal.pone.0307696. eCollection 2024.
It has been reported that Ywhah (14-3-3η) reduces glycolysis. However, it remains unclear about the downstream mechanism by which glycolysis is regulated by 14-3-3η in cardiac hypertrophy. As an important regulator, Yes-associated protein (YAP) interacts with 14-3-3η to participate in the initiation and progression of various diseases in vivo. In this study, the model of H9C2 cardiomyocyte hypertrophy was established by triiodothyronine (T3) or rotenone stimulation to probe into the action mechanism of 14-3-3η. Interestingly, the overexpression of 14-3-3η attenuated T3 or rotenone induced cardiomyocyte hypertrophy and decreased glycolysis in H9C2 cardiomyocytes, whereas the knockdown of 14-3-3η had an opposite effect. Mechanistically, 14-3-3η can reduce the expression level of YAP and bind to it to reduce its nuclear translocation. In addition, changing YAP may affect the expression of lactate dehydrogenase A (LDHA), a glycolysis-related protein. Meanwhile, LDHA is also a possible target for 14-3-3η to mediate glycolysis based on changes in pyruvate, a substrate of LDHA. Collectively, 14-3-3η can suppress cardiomyocyte hypertrophy via decreasing the nucleus translocation of YAP and glycolysis, which indicates that 14-3-3η could be a promising target for inhibiting cardiac hypertrophy.
据报道，Ywhah（14-3-3η）可降低糖酵解。然而，14-3-3η 如何调节心肌肥厚中的糖酵解，其下游机制仍不清楚。作为一个重要的调节剂，Yes 相关蛋白（YAP）与 14-3-3η 相互作用，参与体内各种疾病的发生和发展。在这项研究中，通过三碘甲状腺原氨酸（T3）或鱼藤酮刺激建立 H9C2 心肌细胞肥大模型，以探讨 14-3-3η 的作用机制。有趣的是，14-3-3η 的过表达可减弱 T3 或鱼藤酮诱导的 H9C2 心肌细胞肥大和糖酵解，而 14-3-3η 的敲低则有相反的效果。机制上，14-3-3η 可以降低 YAP 的表达水平，并与之结合以减少其核转位。此外，改变 YAP 可能会影响糖酵解相关蛋白乳酸脱氢酶 A（LDHA）的表达。同时，LDHA 也可能是 14-3-3η 介导糖酵解的一个潜在靶点，基于其对 LDHA 底物丙酮酸的变化。总之，14-3-3η 可以通过减少 YAP 的核转位和糖酵解来抑制心肌肥大，这表明 14-3-3η 可能是抑制心肌肥大的有前途的靶点。
