Impaired surfactant synthesis in fetal type II lung cells from gsd/gsd rats.
The importance of intracellular glycogen for surfactant synthesis was investigated in fetal type II lung cells isolated from rats with a glycogen storage disorder, designated gsd/gsd. Compared to cells from a control Wistar strain, cultured gsd/gsd pneumocytes were glycogenrich and contained fewer and smaller lamellar inclusions. Freshly isolated cells from day 19-21 fetuses of control rats demonstrated the expected gestational rise and fall of cellular glycogen seen in intact fetal lungs. At day 20, when tissue glycogen peaks, cellular glycogen content was 48 and 70 nmol glucose/micrograms DNA in isolated type II cells of control and gsd/gsd lungs, respectively. In control cells, while active glycogen phosphorylase changed from 35 to 65% of total during 24 h of culture, glycogen fell 85%. In contrast, gsd/gsd cell phosphorylase was not activated, phosphorylase kinase activity was nondetectable, and glycogen per cell remained unchanged. [3H]Choline incorporation into total PC and disaturated PC (DSPC) was 50 and 62% lower, respectively, in gsd/gsd type II cells compared to controls in the absence of exogenous substrate. Cellular content of the surfactant-associated protein SP-A was similar in control and gsd/gsd cells at day 20, and increased 3- to 4-fold during a subsequent 24-h interval of tissue culture. These results suggest that PC synthesis is dramatically impaired in type II cells in which glycogen cannot be mobilized, but SP-A is synthesized at normal rates. This work characterizes the isolated gsd/gsd fetal type II cell and supports its use in future studies to determine the importance and relative utilization of specific nonglycogen substrates.
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Department of Cellular and Molecular Physiology, Pennsylvania State University, Hershey 17033, USA.
D000818:Animals; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005325:Fetal Organ Maturity; D005865:Gestational Age; D006003:Glycogen / Q000378:metabolism*; D008168:Lung / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D011663:Pulmonary Surfactants; D006003:Glycogen