Identification of a unique form of protein C in the ovine fetus: developmentally linked transition to the adult form.
To investigate fetal development of protein C, a pregnant ovine model was used. Protein C was isolated from ovine plasma, and a polyclonal antibody was raised. Citrated plasma was obtained from undisturbed chronically catheterized fetal lambs. On Western blot, nonreduced adult ovine protein C had a molecular mass of 70 kD. Fetal ovine protein C was determined to have a molecular mass of 4 to 6 kD larger than the adult molecule. Crossed immunoelectrophoresis demonstrated slightly increased anodal migration of the fetal form. Isoelectric focusing demonstrated a decreased pI of the fetal molecule (4.45 versus 4.6). The ovine protein C molecules were deglycosylated with N-glycanase. Deglycosylated fetal protein C migrated more similarly to the adult form, although a portion of the fetal form persisted. These experiments demonstrate the first example of a unique fetal form of a vitamin K-dependent protein and are compatible with increased glycosylation of fetal ovine protein C. It is speculated that altered posttranslational processing may exist as a general process by which certain coagulation proteins are modified during fetal development. mRNA was isolated from maternal and fetal hepatic tissue and analyzed by Northern hybridization. Fetal plasma concentration and hepatic mRNA for protein C were both 40% of normal maternal values from midgestation onward. At term, protein C mRNA increased to adult range (p < 0.025), although plasma protein C concentration decreased slightly (p < 0.001). A transition from fetal to adult protein C form was found beginning 6 d before term birth, with a doubling time of 24 h. These data are compatible with a gestationally determined maturation of ovine protein C.(ABSTRACT TRUNCATED AT 250 WORDS)
Manco-Johnson
M J
MJ
Department of Pediatrics, University of Colorado Health Sciences Center, Denver 80262, USA.
Spedale
S
S
Peters
M
M
Townsend
S F
SF
Jacobson
L J
LJ
Christian
J
J
Krugman
S D
SD
Hay
W W
WW
Sparks
J W
JW
D000375:Aging / Q000097:blood; D000818:Animals; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D005326:Fetal Proteins / Q000032:analysis*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D011486:Protein C / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep
D005326:Fetal Proteins; D011486:Protein C; D012333:RNA, Messenger