Basil and Gerald Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Petach-Tikva 49100, Israel.
Int J Mol Med. 2011 Jan;27(1):25-31. doi: 10.3892/ijmm.2010.558. Epub 2010 Nov 10.
Congestive heart failure, a complex disease of heterogeneous etiology, involves alterations in the expression of multiple genes. The Popeye domain-containing (POPDC) family of three novel muscle-restricted genes (POPDC1-3) is evolutionarily conserved and developmentally regulated. In mice, POPDC1 has been shown to play an important role in skeletal and cardiac muscles subjected to injury or stress. However, it has never been explored in human hearts. In biopsies from non-failing and failing human hearts, we examined the cellular distribution of POPDC1 as well as the expression patterns of POPDC1-3 mRNAs. POPDC1 was visualized by immunohistochemistry and estimated by Western immunoblotting. The mRNA levels of POPDC1-3 and ß myosin heavy chain (MYHC7) were assessed using reverse transcription/quantitative polymerase chain reaction. POPDC1 was predominantly localized in the sarcolemma with an enhanced expression in the intercalated discs. In failing hearts, many cardiomyocytes appeared deformed and POPDC1 labeling was deranged. The three POPDC mRNAs were expressed in the four heart chambers with higher transcript levels in the ventricles compared to the atria. Heart failure concurred with reduced levels of POPDC1 mRNA and protein in the left ventricle. Correlation analyses of mRNA levels among the failing heart specimens indicated the coordinated regulation of POPDC1 with POPDC3 and of POPDC2 with MYHC7. It can be concluded that POPDC gene expression is modified in end-stage heart failure in humans in a manner suggesting regulatory and/or functional differences between the three family members and that POPDC1 is particularly susceptible to this condition.
充血性心力衰竭是一种病因复杂的异质性疾病，涉及多个基因表达的改变。三个新型肌肉特异性基因（POPDC1-3）的 Popeye 结构域家族在进化上是保守的，并且受发育调控。在小鼠中，POPDC1 已被证明在受到损伤或应激的骨骼肌和心肌中发挥重要作用。然而，在人类心脏中从未进行过探索。在非衰竭和衰竭的人类心脏活检中，我们检查了 POPDC1 的细胞分布以及 POPDC1-3 mRNA 的表达模式。通过免疫组织化学观察 POPDC1，并通过 Western 免疫印迹进行估计。使用逆转录/定量聚合酶链反应评估 POPDC1-3 和ß肌球蛋白重链（MYHC7）的 mRNA 水平。POPDC1 主要定位于肌膜，在闰盘处表达增强。在衰竭的心脏中，许多心肌细胞变形，POPDC1 标记异常。三个 POPDC mRNA 在四个心腔中表达，与心房相比，心室中的转录物水平更高。与左心室相比，心力衰竭时 POPDC1 mRNA 和蛋白水平降低。衰竭心脏标本中 mRNA 水平的相关分析表明，POPDC1 与 POPDC3 的协调调节以及 POPDC2 与 MYHC7 的协调调节。可以得出结论，在人类终末期心力衰竭中，POPDC 基因表达发生改变，提示三个家族成员之间存在调节和/或功能差异，并且 POPDC1 特别容易受到这种情况的影响。
