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失去Mdm4会导致p53依赖的扩张性心肌病
Shunbin Xiong1, Carolyn S Van Pelt, Ana C Elizondo-Fraire
1Department of Cancer Genetics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Circulation
|May 30, 2007
概括
成人心脏细胞中Mdm4蛋白质的损失会导致小鼠的扩张性心肌病 (DCM). 这种p53依赖心肌细胞的亡模仿了人类的DCM,并提出了一个新的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 分子遗传学 分子遗传学
- 细胞死亡途径 细胞死亡途径
背景情况:
- 家庭扩张性心肌病 (DCM) 的起源通常是未知的.
- Mdm2和Mdm4调节p53,一种瘤抑制剂.
- 在成人心肌细胞和DCM中Mdm4的作用尚未被探索.
研究的目的:
- 为了研究Mdm4在成人心肌细胞中的功能.
- 为了确定Mdm4缺乏是否与DCM有关.
主要方法:
- 在成年老鼠心脏中使用心肌细胞特异性Cre.
- 对心脏功能,存活率和心肌细胞亡的分析.
- 评估p53通路的参与.
主要成果:
- 成年人心脏中的Mdm4删除导致DCM和降低生存率.
- 在男性中,DCM的发病时间较早,反映了人类的疾病.
- 心肌细胞亡,依赖于p53,导致DCM.
结论:
- 在分化心肌细胞中,Mdm4抑制p53.
- 通过p53介导的心肌细胞亡是DCM的一个潜在机制.
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