Increased N-glycosylation and reduced transferrin-binding capacity of transferrin receptor isolated from placentae of diabetic women.
Infants of diabetic mothers are frequently born iron deficient because their fetal iron demand exceeds placental iron transport capacity. Although transferrin receptor (TfR) expression is increased, binding to diferric transferrin is decreased proportionately to the severity of maternal disease. It is hypothesized that TfR isolated from diabetic placentae has altered N-glycosylation since proper glycosylation of N-linked oligosaccharides is important for normal TfR binding kinetics to diferric transferrin. TfR was obtained from syncytiotrophoblastic membranes of six diabetic and six non-diabetic human placentae. Competitive binding to 125I-transferrin demonstrated a higher Kd in the diabetic TfR (P = 0.04), directly correlated to cord serum C-peptide concentration (r = 0.81, P < 0.001). The molecular weight of the monomeric form of TfR prior to treatment with glycopeptidase F (PNG-F) was greater in the diabetic group (P < 0.001) was directly related to the Kd (r = 0.77, P = 0.002). Treatment with PNG-F eliminated the molecular weight difference between the two groups. Increased glycosylation of the N-linked oligosaccharides of TfR isolated from diabetic placentae may alter the three-dimensional structure or charge of the receptor, thus reducing its binding affinity for transferrin.
Georgieff
M K
MK
Division of Neonatology, Department of Minnesota School of Medicine, Minneapolis, USA. geog001@maroon.tc.umn.edu
Petry
C D
CD
Mills
M M
MM
McKay
H
H
Wobken
J D
JD
D001667:Binding, Competitive; D002096:C-Peptide / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005865:Gestational Age; D006031:Glycosylation; D006801:Humans; D008970:Molecular Weight; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*; D014327:Trophoblasts / Q000737:chemistry / Q000378:metabolism
D002096:C-Peptide; D011990:Receptors, Transferrin; D014168:Transferrin