Kim W H, Joo C U, Ku J H, Ryu C H, Koh K N, Koh G Y, Ko J K
Department of Obstetrics and Gynecology, Chonbuk National University Medical School, Chonju, Korea.
Korean J Intern Med. 1998 Jul;13(2):77-82. doi: 10.3904/kjim.1998.13.2.77.
The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans.
Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery. Cyclin and CDK proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate.
Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP1 protein increased markedly in the adult period, while p21CIP1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period.
These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans.
调节人类心肌细胞细胞周期和终末分化的分子机制在很大程度上仍不清楚。为了确定哪些细胞周期蛋白、细胞周期蛋白依赖性激酶（CDK）和细胞周期蛋白激酶抑制剂（CKI）对心肌细胞增殖很重要，我们检测了人类正常心房发育过程中细胞周期蛋白、CDK和CKI的蛋白水平。
从难免流产的胎儿和手术中的成年人获取心房组织。通过蛋白质印迹分析确定细胞周期蛋白和CDK蛋白。使用特异性底物通过磷酸化量确定CDK活性。
大多数细胞周期蛋白和CDK在胎儿期含量较高，在成年期其水平以不同速率下降。虽然细胞周期蛋白D1、细胞周期蛋白D3、CDK4、CDK6和CDK2的蛋白水平在成年心房中仍可检测到，但细胞周期蛋白E、细胞周期蛋白A、细胞周期蛋白B、cdc2和增殖细胞核抗原（PCNA）的蛋白水平无法检测到。有趣的是，p27KIP1蛋白在成年期显著增加，而心房中的p21CIP1蛋白仅在胎儿期可检测到。虽然CDK6、CDK2和cdc2的活性显著下降，但CDK4的活性从胎儿期到成年期没有变化。
这些发现表明，细胞周期蛋白和CDK的蛋白水平和活性显著降低，以及心房中p27KIP1的显著诱导，与成年人类心脏细胞周期的退出有关。
