Liang Jiayi, Xie Qiang, Li Ping, Zhong Xueyun, Chen Yunxian
Department of Hematology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
Mol Cell Biochem. 2015 Mar;401(1-2):71-86. doi: 10.1007/s11010-014-2293-y. Epub 2014 Dec 19.
Previous studies reported that estrogen receptor β (ERβ) is localized to mitochondria, whereas little is known about the physiological functions of mitochondrial ERβ. In the present study, we explored the role of mitochondrial ERβ in regulating apoptosis using stable ERβ-expressing and ERβ knockdown cells lines. We found that exogenous ERβ was mainly expressed in mitochondrial but not in nuclear after ERβ overexpression and protected cells from apoptosis induced by hydrogen peroxide (H₂O₂), ultraviolet (UV), and staurosporine (STS). Moreover, overexpression of ERβ prevented Bax activation, cytochrome c release, caspase-3 activation, and PARP cleavage during apoptosis. Furthermore, knockdown of ERβ significantly suppressed the expression of ERβ in mitochondrial and promoted cell apoptosis induced by H₂O₂, UV, and STS. Downregulation of ERβ also enhanced Bax activation, cytochrome c release, caspase-3 activation and PARP cleavage. In addition, our study discovered that mitochondrial ERβ interacted with proapoptotic protein Bad in a ligand-independent manner, which suggests that mitochondrial ERβ inhibits Bad, and prevents Bax activation and cytochrome c release. Collectively, the results of this study support that mitochondrial ERβ prevents cell apoptosis via the mitochondrial apoptotic pathway in a ligand-independent manner.
先前的研究报道雌激素受体β（ERβ）定位于线粒体，而关于线粒体ERβ的生理功能却知之甚少。在本研究中，我们利用稳定表达ERβ和敲低ERβ的细胞系，探讨了线粒体ERβ在调节细胞凋亡中的作用。我们发现，ERβ过表达后，外源性ERβ主要在线粒体中表达，而不在细胞核中表达，并保护细胞免受过氧化氢（H₂O₂）、紫外线（UV）和星形孢菌素（STS）诱导的细胞凋亡。此外，ERβ的过表达在细胞凋亡过程中阻止了Bax激活、细胞色素c释放、caspase-3激活和PARP裂解。此外，敲低ERβ显著抑制了线粒体中ERβ的表达，并促进了由H₂O₂、UV和STS诱导的细胞凋亡。ERβ的下调还增强了Bax激活、细胞色素c释放、caspase-3激活和PARP裂解。此外，我们的研究发现线粒体ERβ以不依赖配体的方式与促凋亡蛋白Bad相互作用，这表明线粒体ERβ抑制Bad，并阻止Bax激活和细胞色素c释放。总的来说，本研究结果支持线粒体ERβ以不依赖配体的方式通过线粒体凋亡途径阻止细胞凋亡。
