抑制性心脏转录因子SRF-N是由人类心力衰竭中的caspase 3裂变产生的,并通过心室卸载减弱
Jiang Chang1, Lei Wei, Takayuki Otani
1Department of Molecular and Cellular Biology, Center for Cardiovascular Development, Methodist Hospital, Baylor College of Medicine, One Baylor Plaza, Houston, Tex 77030, USA.
Circulation
|July 23, 2003
概括
在心力衰竭中,caspase 3分裂血清响应因子 (SRF),产生抑制心脏基因的主导负因子. 这种SRF裂纹在心室卸载时可能是可逆的.
科学领域:
- 分子生物学分子生物学
- 心血管研究的心血管研究.
- 生物化学 生物化学
背景情况:
- 心力衰竭的特点是基因活性降低和适度的caspase 3激活.
- 心脏转录因子血清反应因子 (SRF) 在心力衰竭中的作用尚未完全理解.
- 我们假设caspase 3分裂SRF,抑制其功能并导致心力衰竭.
研究的目的:
- 调查血清响应因子 (SRF) 是否是末期心力衰竭中caspase 3的裂解标.
- 为了确定在失败的心脏中SRF裂变的功能后果.
主要方法:
- 从心力衰竭患者和正常对照患者的人类心脏样本中分析SRF蛋白水平和碎片化.
- 在使用左心室辅助器件的患者中调查SRF碎片化.
- 在SRF上使用抗体和部位定向突变发生的方法识别caspase 3裂变部位.
- 在肌细胞中评估SRF片段的转录活性.
主要成果:
- 全长SRF在心脏衰竭中显著减少和碎片化,但在正常心脏中完好无损.
- 在带有左心室辅助装置的心脏中观察到最小的SRF碎片化.
- 确定了两个替代的酶3裂解点,产生N端和C端SRF碎片.
- 32kDa N-终端SRF片段 (SRF-N) 的表达抑制了50-60%的α-actin基因促进活性.
结论:
- 在心力衰竭中,卡斯帕酶3的激活会顺序地切割SRF,产生主导负的转录因子.
- 这一过程可能解释了心力衰竭中心脏特异性基因的下调.
- 卡斯帕酶3激活和随后的SRF裂变在心室卸载时可能是可逆的.
关键词:
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