Abstract
BackgroundMammalian cardiac myocytes withdraw from the cell cycle during post-natal development, resulting in a non-proliferating, fully differentiated adult phenotype that is unable to repair damage to the myocardium, such as occurs following a myocardial infarction. We and others previously have shown that forced expression of certain cell cycle molecules in adult cardiac myocytes can promote cell cycle progression and division in these cells. The mitotic serine/threonine kinase, Polo-like kinase-1 (Plk1), is known to phosphorylate and activate a number of mitotic targets, including Cdc2/Cyclin B1, and to promote cell division.Principal FindingsThe mammalian Plk family are all differentially regulated during the development of rat cardiac myocytes, with Plk1 showing the most dramatic decrease in both mRNA, protein and activity in the adult. We determined the potential of Plk1 to induce cell cycle progression and division in cultured rat cardiac myocytes. A persistent and progressive loss of Plk1 expression was observed during myocyte development that correlated with the withdrawal of adult rat cardiac myocytes from the cell cycle. Interestingly, when Plk1 was over-expressed in cardiac myocytes by adenovirus infection, it was not able to promote cell cycle progression, as determined by cell number and percent binucleation.ConclusionsWe conclude that, in contrast to Cdc2/Cyclin B1 over-expression, the forced expression of Plk1 in adult cardiac myocytes is not sufficient to induce cell division and myocardial repair.
Highlights
Mammalian cardiac myocytes lose the ability to divide shortly after birth, [1,2,3,4], differentiating into cell cycle arrested binucleated cells
Based upon previous studies showing the downregulation of positive regulators of cell cycle molecules during cardiac myocyte development, we hypothesized that the expression of Polo-like kinase-1 (Plk1) would be downregulated as these cells progressed towards full differentiation
Quantitative PCR analysis revealed a progressive decline in Plk1 mRNA levels during development (Figure 1A) and this was seen at the protein level (Figure 1B)
Summary
Mammalian cardiac myocytes lose the ability to divide shortly after birth, [1,2,3,4], differentiating into cell cycle arrested binucleated cells. The change in growth potential of cardiac myocytes during cardiac development and hypertrophy is reflected in the expressions and activities of certain cell cycle molecules.[8,9,10,11,12,13,14,15] positive regulators of the cell cycle machinery, such as the Cdk/cyclin complexes and the pro-proliferative E2F transcription factors (E2F1-3) are down regulated, whilst negative regulators, including retinoblastoma protein (pRb) and the cyclin-dependent kinase inhibitors (CDKIs), p21 and p27, are upregulated. Mammalian cardiac myocytes withdraw from the cell cycle during post-natal development, resulting in a nonproliferating, fully differentiated adult phenotype that is unable to repair damage to the myocardium, such as occurs following a myocardial infarction. The mitotic serine/ threonine kinase, Polo-like kinase-1 (Plk1), is known to phosphorylate and activate a number of mitotic targets, including Cdc2/Cyclin B1, and to promote cell division
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
