Estrogen receptor beta interacts and colocalizes with HADHB in mitochondria.

Estrogen receptor beta interacts and colocalizes with HADHB in mitochondria.
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DOI:
10.1016/j.bbrc.2012.09.047
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发表时间:
2012-10-19
影响因子:
3.1
通讯作者:
Du, Yuchun
Du, Yuchun
中科院分区:
生物学4区
文献类型:
--
作者:
Zhou, Zhenqi;Zhou, Jianhong;Du, Yuchun

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雌激素受体定位于线粒体,但其在该细胞器中的功能尚不清楚。我们先前发现ERα与线粒体蛋白HADHB相互作用,并影响HADHB在β氧化中的硫解切割活性。已知ERβ与ERα结合。此外,ERβ主要定位于线粒体。这些事实使我们推测,线粒体中的ERβ可能也与HADHB有关。为了验证这一假设,我们对人乳腺癌MCF7细胞进行了免疫共沉淀和共聚焦显微镜分析。结果表明,内质网β确实与HADHB在线粒体内存在联系和共存。有趣的是,与先前研究中观察到的ERα对HADHB酶活性的刺激作用相反,在本研究中,沉默ERβ增强了HADHB的酶活性,表明ERβ对乳腺癌细胞的HADHB酶活性具有抑制作用。我们的结果提示,ERα和ERβ可能通过影响乳腺癌细胞中脂肪酸的β氧化速率而不同地影响细胞的氧化应激。
Estrogen receptors are localized in mitochondria, but their functions in this organelle remain unclear. We previously found that ERα interacted with mitochondrial protein HADHB and affected the thiolytic cleavage activity of HADHB in β-oxidation. It is known that ERβ binds to ERα. In addition, ERβ is predominately located in mitochondria. These facts led us to speculate that ERβ may also be associated with HADHB in mitochondria. In order to test this hypothesis, we performed co-immunoprecipitation and confocal microscopy analyses with human breast cancer MCF7 cells. The results demonstrated that ERβ was indeed associated and colocalized with HADHB within mitochondria. Interestingly, in contrast to the stimulatory effect of ERα on HADHB enzyme activity observed in the previous study, silencing of ERβ enhanced the enzyme activity of HADHB in the present study, suggesting that ERβ plays an inhibitory role in HADHB enzyme activity in the breast cancer cells. Our results imply that ERα and ERβ may differentially affect cellular oxidative stress through influencing the rate of β-oxidation of fatty acids in breast cancer cells.
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