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Localization of proliferating cell nuclear antigen in the developing and mature rat heart cell
T A Marino1, W Cao, J Lee
1Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. marino@astro.ocis.temple.edu
The Anatomical Record
|August 1, 1996
Summary
Cardiac muscle cell division and DNA synthesis cease after birth, linked to declining levels of proliferating cell nuclear antigen (PCNA) protein, which is not found in adult cell nuclei.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Biology
- Developmental Biology
Background:
- Cardiac muscle cells stop dividing shortly after birth.
- A limited window exists for DNA synthesis and karyokinesis without cytokinesis.
- Regulation of this process remains largely unknown.
Purpose of the Study:
- To investigate potential mechanisms regulating cardiac muscle cell division cessation.
- To explore the role of proliferating cell nuclear antigen (PCNA) in this process.
Main Methods:
- Isolated cardiac myocytes from rats at various fetal and postnatal ages (fetal day 18, postnatal days 0, 4, 8, 12, 16, and adult).
- Assessed DNA synthesis using tritiated thymidine incorporation.
- Analyzed messenger RNA (mRNA) and protein levels of PCNA via Northern and Western blotting and immunofluorescence.
Main Results:
- Serum stimulation increased DNA synthesis in fetal, but not neonatal, cardiac myocytes.
- PCNA mRNA levels remained constant until the second postnatal week, then declined.
- PCNA protein was nuclear in the first two postnatal weeks, shifting to the cytoplasm and diminishing by day 16 and in adults.
Conclusions:
- PCNA expression and nuclear localization decrease significantly after birth in cardiac muscle cells.
- These changes in PCNA correlate with the cessation of cell division and DNA synthesis.
- PCNA's nuclear translocation appears critical for continued DNA synthesis in cardiac myocytes.