PI3K/AKT/mTOR通路
自噬
蛋白激酶B
雌激素受体
内分泌学
内科学
血管紧张素II
化学
雌激素
肌肉肥大
受体
细胞生物学
信号转导
生物
医学
细胞凋亡
生物化学
癌症
乳腺癌
作者
Hui Peng,Wei Wang,Di Zhao,Hongyan Su,Guohai Su,Zhuo Zhao
摘要
Estrogen has been demonstrated to protect the heart against cardiac remodelling and heart failure in women. G protein-coupled estrogen receptor 1 (GPER1) is a recently discovered estrogen receptor (ER) that is expressed in various tissues. However, the mechanisms by which estrogen protects the heart, especially the roles played by ERs, are not clear. In this study, we explored the effect of GPER1 activation on angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and the involved signalling pathways and mechanisms. Our data demonstrated that GPER1 is expressed in cardiomyocytes, a GPER1 agonist, G1, attenuated Ang II-induced cardiomyocyte hypertrophy and downregulated the mRNA expression levels of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). Bioinformatics analysis revealed that five proteins, including RAP1gap, might be the key proteins involved in the attenuation of Ang II-induced cardiomyocyte hypertrophy by GPER1. G1 increased the protein level of p-Akt, p-70S6K1 and p-mTOR but decreased p-4EBP1 expression. All these effects were inhibited by either G15 (a GPER1 antagonist) or MK2206 (an inhibitor of Akt). Autophagy analysis showed that the LC3II/LC3I ratio was increased in Ang II-treated cells, and the increase was inhibited by G1 treatment. The effect of G1 on autophagy was blocked by treatment with G15, rapamycin, and MK2206. These results suggest that GPER1 activation attenuates Ang II-induced cardiomyocyte hypertrophy by upregulating the PI3K-Akt-mTOR signalling pathway and inhibiting autophagy.
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