Department of Anatomy, College of Basic Medicine, Guilin Medical University, Guilin, Guangxi, 541004, China; Clinical Pathology Department, The Second People's Hospital of China Three Gorges University, Yichang, Hubei, 443600, China.
Department of Anatomy, College of Basic Medicine, Guilin Medical University, Guilin, Guangxi, 541004, China.
Mol Cell Endocrinol. 2024 Sep 1;590:112271. doi: 10.1016/j.mce.2024.112271. Epub 2024 May 15.
Hyperthyroidism is becoming increasingly important as an independent risk factor for cardiovascular disease, eventually resulting in cardiac hypertrophy and heart failure. The 14-3-3 protein family subtypes regulate many cellular processes in eukaryotes by interacting with a diverse array of client proteins. Considering that the 14-3-3η protein protects cardiomyocytes by affecting mitochondrial function, exploring the biological influence and molecular mechanisms by which 14-3-3η alleviates the cardiac hypertrophy of hyperthyroidism is imperative. In vivo and in vitro, RT-PCR, Western blot, and Mitochondrial tracking assay were performed to understand the molecular mechanism of thyroxine-induced cardiomyocyte hypertrophy. HE staining, transmission electron microscopy, and immunofluorescence were used to observe intuitively changes of hearts and cardiomyocytes. The in vivo and in vitro results indicated that overexpression of the 14-3-3η ameliorated thyroxine-induced cardiomyocyte hypertrophy, whereas knockdown of the 14-3-3η protein aggravated thyroxine-induced cardiomyocyte hypertrophy. Additionally, overexpression of the 14-3-3η protein reduces thyroxine-induced mitochondrial damage and mitophagy in cardiomyocytes. Overexpression of 14-3-3η protein improves excessive mitophagy in the myocardium caused by thyroxine and thus prevents cardiac hypertrophy.
甲状腺功能亢进症作为心血管疾病的独立危险因素变得越来越重要，最终导致心肌肥厚和心力衰竭。14-3-3 蛋白家族亚型通过与多种不同的客户蛋白相互作用来调节真核生物中的许多细胞过程。鉴于 14-3-3η 蛋白通过影响线粒体功能来保护心肌细胞，因此研究 14-3-3η 减轻甲状腺功能亢进引起的心肌肥厚的生物学影响和分子机制至关重要。在体内和体外，通过 RT-PCR、Western blot 和线粒体追踪分析来了解甲状腺素诱导的心肌细胞肥大的分子机制。通过 HE 染色、透射电子显微镜和免疫荧光观察直观地观察心脏和心肌细胞的变化。体内和体外结果表明，14-3-3η 的过表达改善了甲状腺素诱导的心肌细胞肥大，而 14-3-3η 蛋白的敲低则加重了甲状腺素诱导的心肌细胞肥大。此外，14-3-3η 蛋白的过表达减少了甲状腺素诱导的心肌细胞中线粒体损伤和自噬。14-3-3η 蛋白的过表达改善了甲状腺素引起的心肌中过度的自噬，从而防止了心肌肥厚。
