雌激素受体β激活导致参与心脏保护的蛋白质的S-化

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Jeffrey Lin¹, Charles Steenbergen, Elizabeth Murphy

¹Harvard Medical School, Boston, MA, USA.

Circulation

|July 8, 2009

概括

雌激素受体-β (ER-β) 激活通过增加蛋白质S-化 (SNO) 来保护心脏免受缺血/反损伤. 这种机制突显了ER-β和氧化信号在长期雌激素介导的心脏保护中.

科学领域:

心血管生物学心血管生物学
内分泌学在内分泌学.
分子医学是分子医学.

背景情况:

已知雌激素受体-β (ER-β) 激活有助于预防缺血/反 (I/R) 损伤的心脏保护作用.
基础ER-β介导心脏保护的精确分子机制尚不清楚.
假设雌激素的保护作用涉及ER-β激活,导致关键蛋白质的S-化 (SNO).

研究的目的:

调查ER-β激活在介导心脏保护对I/R损伤中的作用.
阐明ER-β激活赋予保护的机制,特别是研究蛋白质S-化酶的作用.
确定ER-β选择性激动剂是否可以复制雌激素的心脏保护作用.

主要方法:

经过卵巢切除的小鼠被用ER-β选择性激动剂 (DPN) 或17β-雌激醇 (E2) 治疗了两周.
隔离的心脏经历了兰根多夫输液,随后是缺血和再输液.
使用2D DyLight光差凝电泳的蛋白质组分析被用来量化蛋白质S-化.
用氧化合成酶抑制来评估氧化在观察到的影响中的作用.

主要成果:

与车辆对照组相比,DPN和E2治疗显著改善了后缺血功能恢复和减少了心脏病发作的大小.
在接受DPN治疗的ER-β绝杀性小鼠中,心脏保护被取消,证实了ER-β的特异性.
DPN和E2治疗增加了几种蛋白质的S-化,其中一些已知在预先条件的心脏中被化.
心脏保护作用和增加的蛋白质SNO被氧化合成酶抑制取消.

结论:

通过DPN治疗激活ER-β,可以显著地保护心脏免受缺血/反损伤的影响.
增加蛋白质S-化是调解ER-β诱导心脏保护的关键机制.
长期暴露于雌激素可能主要通过ER-β激活和氧化/SNO信号通路保护心脏.

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