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.
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 approximately 25 hours in fresh aortic tissues to approximately 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 approximately 25 hours in the 1-day-old chicken to approximately 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.
Johnson
D J
DJ
Division of Cardiovascular Research, Hospital for Sick Children, Toronto, Canada.
Robson
P
P
Hew
Y
Y
Keeley
F W
FW
D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D004247:DNA / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004549:Elastin / Q000096:biosynthesis* / Q000235:genetics*; D006207:Half-Life; D009924:Organ Culture Techniques; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic
D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D004004:Dichlororibofuranosylbenzimidazole; D004247:DNA; D004549:Elastin