Max-Planck-Institut for Heart und Lung Research, D-61231 Bad Nauheim, Germany.
Circ Res. 2010 May 14;106(9):1498-506. doi: 10.1161/CIRCRESAHA.109.211888. Epub 2010 Apr 1.
Polyploidy and multinucleation are characteristic features of mammalian cardiomyocytes, which develop shortly after birth when most differentiated cardiomyocytes become acytokinetic. Cardiac overload and hypertrophy further increase the degree of polyploidy of cardiomyocytes, suggesting a role in cell type-specific responses to physiological and pathological stimuli.
We sought to study the function of cyclinG1 in the regulation of polyploidy and multinucleation in cardiomyocytes.
We found that expression of cyclinG1, a transcriptional target of p53, coincides with arrest of cardiomyocyte proliferation and onset of polyploidization. Overexpression of cyclinG1 promoted DNA synthesis but inhibited cytokinesis in neonatal cardiomyocytes leading to an enlarged population of binuclear cardiomyocytes. Reciprocally, inactivation of the cyclinG1 gene in mice lowered the degree of polyploidy and multinucleation in cardiomyocytes. Moreover, lack of cyclinG1 prevented the increase of polynucleated cardiomyocytes in response to pressure overload and hypertrophy.
CyclinG1 is an important player for the regulation of polyploidy and multinucleation in cardiomyocytes probably by inhibition of apoptosis caused by checkpoint activation.
多倍体和多核是哺乳动物心肌细胞的特征，这些细胞在出生后不久就会发育，此时大多数分化的心肌细胞成为无丝分裂细胞。心脏负荷过重和肥大进一步增加了心肌细胞的多倍体程度，表明其在细胞类型特异性对生理和病理刺激的反应中起作用。
我们试图研究细胞周期蛋白 G1 在调节心肌细胞多倍体和多核中的作用。
我们发现，细胞周期蛋白 G1 的表达与心肌细胞增殖的停滞和多倍体化的开始相吻合，细胞周期蛋白 G1 是 p53 的转录靶点。细胞周期蛋白 G1 的过表达促进了新生儿心肌细胞的 DNA 合成，但抑制了胞质分裂，导致双核心肌细胞的数量增加。相反，在小鼠中敲除 cyclinG1 基因可降低心肌细胞的多倍体和多核程度。此外，缺乏 cyclinG1 可防止压力超负荷和肥大引起的多核心肌细胞数量增加。
细胞周期蛋白 G1 是调节心肌细胞多倍体和多核的重要因素，可能通过抑制检查点激活引起的细胞凋亡来实现。
