© 1995 American Heart Association, Inc.
Articles |
Decreased Elastin Synthesis in Normal Development and in Long-term Aortic Organ and Cell Cultures Is Related to Rapid and Selective Destabilization of mRNA for Elastin
From the Division of Cardiovascular Research, Hospital for Sick Children, Toronto, Canada, and the Departments of Biochemistry and Clinical Biochemistry, University of Toronto.
Correspondence to Dr F.W. Keeley, Division of Cardiovascular Research, Hospital for Sick Children, 555 University Ave, Toronto, Canada, M5G 1X8. E-mail fwk@resunix.ri.sickkids.on.ca.
Abstract We have previously shown that aortic organ cultures
from 1- to 3-day-old chickens initially mimic the high levels of
elastin production seen in vivo. However, more prolonged
incubation of these tissues results in decreased synthesis of elastin.
In the present study, we demonstrate that decreased
production of elastin in these aortic organ cultures is
selective for elastin compared with collagen and is correlated with
decreased steady state levels of mRNA for elastin. These decreases in
steady state levels of elastin mRNA are due at least in part to a rapid
and selective destabilization of mRNA for elastin, the half-life of
which falls from 
25 hours in fresh aortic tissues to 15 hours
after incubation for only 8 hours. Destabilization of elastin mRNA can
be prevented by incubation in the presence of blockers of DNA
transcription (5,6-dichlorobenzimidazole riboside and actinomycin D)
and mRNA translation (cycloheximide). Furthermore, the half-life of
aortic elastin mRNA decreases from 25 hours in the 1-day-old
chicken to 7 hours in the 8-week-old chicken, demonstrating that
destabilization of mRNA is an important contributing factor in the
decline in production of aortic elastin taking place during
normal postnatal growth.
Key Words: elastin • mRNA turnover • aorta • organ culture • development
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