No evidence for vitamin K-dependent carboxylation of canine surfactant apoproteins, 28-36 kDa.
Recent research has shown that rat surfactant apoproteins (26-38 kDa) are vitamin K-dependent [Rannels, Gallaher, Wallin & Rannels (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5952-5956]. We have investigated the effect of the vitamin K antagonist warfarin on this family of apoproteins in surfactant from dog lung. Our data suggest that warfarin does not interfere with synthesis and secretion of these proteins into dog lung surfactant. Abnormal surfactant apoproteins, produced in response to warfarin treatment of the dog, were also not found in lung surfactant. 4-Carboxyglutamic acid analysis of purified dog apoproteins also failed to detect the vitamin K-modification. When vitamin K-dependent 14C labelling of precursors of vitamin K-dependent proteins was carried out, fluorography of these precursors, when electrophoresed into SDS/polyacrylamide gels, revealed 14C-labelled proteins of apparent molecular mass 74, 46, 42, 34, 31 and 23 kDa. Antibodies produced against purified dog surfactant apoproteins recognized precursors of the surfactant apoproteins in lung microsomes but did not recognize any 14C-labelled carboxylase substrates. These precursors appeared on immunoblots with apparent molecular mass 29, 32, 33 and 50 kDa. Our data suggest that there are significant differences between this class of surfactant apoproteins in the rat and the dog.
Wallin
R
R
Department of Surgery, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Seaton
M
M
Martin
L F
LF
D000818:Animals; D001059:Apoproteins / Q000378:metabolism*; D019735:Carbon-Carbon Ligases; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007122:Immunoelectrophoresis; D007525:Isoelectric Focusing; D008025:Ligases / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014812:Vitamin K / Q000494:pharmacology*; D014859:Warfarin / Q000494:pharmacology
D001059:Apoproteins; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C046616:pulmonary surfactant apoprotein; D014812:Vitamin K; D014859:Warfarin; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase