Abstract
Antibodies directed against the major apoprotein of rabbit lung surfactant, a 29-36-kDa glycoprotein, were used to study changes in the levels of translatable surfactant apoprotein mRNA in rabbit lung tissue during development, as well as the effects of cortisol and cyclic AMP analogues on the levels of surfactant apoprotein and its mRNA in fetal rabbit lung tissue in organ culture. The major surfactant apoprotein and its mRNA were undetectable in lung tissues of 21-day gestational age fetal rabbits. Translatable mRNA specific for the major surfactant apoprotein was first detectable in lung tissues of 26-day fetuses, increased 25-fold on day 28, reached peak levels at day 31, and declined after birth. Incubation of 21-day fetal rabbit lung explants with cortisol in serum-free medium resulted in an increase in the specific content of the 29-36-kDa apoprotein. Cyclic AMP analogues and forskolin, an activator of adenylate cyclase, also caused a marked increase in the accumulation of surfactant apoprotein. When fetal lung explants were incubated with cortisol and dibutyryl cyclic AMP in combination, the specific content of the surfactant apoprotein was increased to levels greater than that of explants treated with either cortisol or dibutyryl cyclic AMP alone. These effects of dibutyryl cyclic AMP and cortisol on surfactant apoprotein accumulation were associated with comparable changes in the levels of translatable surfactant apoprotein mRNA. Thus, we have shown for the first time that the induction of pulmonary surfactant apoprotein synthesis during differentiation in vitro and in vivo is associated with an increase in the level of translatable mRNA and that cortisol and cyclic AMP increase both the accumulation of the major surfactant apoprotein and the corresponding mRNA in fetal rabbit lung tissue in vitro.
Highlights
From the Departments of $Biochemistry,Well Biology, and Obstetrics-Gynecology and The Cecil H.and IdaGreen Center for ReproductiveBiology Sciences, University of Texas Health Science Center at Dallas, Dallas, Texas75235
No stimulatory effect of cortisol was detected on day 1;,an increase in phosphatidylcholine synthesis was observed in cortisoltreated explants as compared to controls after 3 and 5 days of incubation
We have demonstrated for the first time that cortisol and cyclic AMP increase the rate of accumulation of the major surfactant apoprotein and its mRNA in fetal rabbit lung tissue
Summary
Cyclic AMP analogues [18,19,20] and phosphodiesterase inhibitors [18, 21,22,23] have been reported to increase surfactant glycerophospholipid synthesisinfetallung tissue. In studiesusing fetal rat lung inorgan culture, Gross and Wilson [27] found that dexamethasone and cyclic AMP act synergistically to increase phosphatidylcholine synthesis. In consideration of the potential importance of surfactantassociated proteins in the biogenesis and structural organization of the lamellar body within the type I1 cell, as well as the possible role of these proteins in surfactant function, it was an objective of the present study to utilize antibodies specific for the major apoprotein of rabbit lung surfactant to investigate developmental changes in thelevels of translatable mRNA specific for this protein and the effect of glucocorticoids and analogues of cyclic AMP on the synthesis of this protein in fetal rabbitlung tissue maintained in uitro
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