Fetal lung development in rats with a glycogen storage disorder.
A New Zealand strain of rats (NZR/Mh) is unable to mobilize liver glycogen due to a deficiency of phosphorylase b kinase. Affected homozygous rats (gsd/gsd) were used to assess the developmental relationship between lung glycogen loss and surfactant phospholipid and protein biosynthesis. Phosphorylase a and phosphorylase b kinase activities were negligible in gsd/gsd fetal lungs compared with controls from gestational day (D18) until postnatal day 1 (D + 1). At D20, tissue glycogen content was 158 +/- 5 and 181 +/- 6 mumol/g lung for control and gsd/gsd, respectively. Control rats mobilized 84% of their lung glycogen by D + 1, whereas the gsd/gsd strain retained 70-80% of D19-20 levels. This apparent fall in gsd/gsd glycogen per gram lung was due to an increase in cellular protein and size. Thus, in controls, total glycogen per lung decreased 65% from D20 to D + 1, whereas DNA doubled. In contrast, gsd/gsd lung growth resulted in a doubling of total lung glycogen, whereas the glycogen-to-DNA ratio remained constant. A lack of cellular glycogenolysis was confirmed by electron microscopy where gsd/gsd type II cells remained large and glycogen-rich over the entire perinatal interval. The potential for glycogen breakdown by a lysosomal alpha-amyloglucosidase in gsd/gsd lungs was estimated in tissue homogenates, whereas rates of hydrolysis of glycogen or p-nitrophenylglucoside were significant and equal to controls at all ages tested. Incorporation of [14C]choline into phosphatidylcholine (PC) of incubated lung slices increased 1.7-fold in control lungs from D20-D21. Over the same interval, PC synthesis in gsd/gsd lungs was 40% lower and did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Rannels
S R
SR
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033.
Rannels
S L
SL
Sneyd
J G
JG
Loten
E G
EG
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D005314:Embryonic and Fetal Development; D006003:Glycogen / Q000378:metabolism; D006008:Glycogen Storage Disease / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D008168:Lung / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D010764:Phosphorylase Kinase / Q000172:deficiency*; D051381:Rats; D011922:Rats, Mutant Strains; D012016:Reference Values
D006003:Glycogen; D010764:Phosphorylase Kinase