The perfused liver is capable of producing all transferrin glycan variants found in the sera of intact rats.
The single oligosaccharide attachment in rat transferrin exhibits marked structural microheterogeneity. In this study we examined whether all microheterogeneous forms of rat transferrin found in plasma are derived from a single organ, such as the liver. To this end we analyzed the glycans of rat transferrin synthesized by the isolated perfused rat liver by a method established earlier for rat transferrin isolated from rat plasma. Our observations provide evidence that the liver can and does produce all variant rat transferrin glycans present in plasma. However, this discovery does not preclude the possibility that extrahepatic sources with an active rat transferrin gene may contribute to the circulation rat transferrin molecules, which bear glycan variants identical to those made by the liver. The glycan spectra of rat transferrin in plasma and in liver perfusate compared closely with each other in a quantitative sense. Nevertheless, rat transferrin in the perfusate was sialylated to a lesser extent and fucosylated to a greater extent than rat transferrin in plasma. These differences could not be eliminated by supplementation of the medium with insulin, dexamethasone, pyruvate and adenine or adenosine either alone or in combinations, nor could it be eliminated by use of a fluorocarbon O2 carrier. In contrast, epidermal growth factor normalized both parameters. The pH of the perfusing medium also influenced sialylation and fucosylation in such a way that higher pH brought these parameters closer to their values in plasma rat transferrin. Lower pH, on the other hand, reduced sialylation and left the fucosylation index unchanged.
Hu
W L
WL
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Chindemi
P A
PA
Regoeczi
E
E
D000818:Animals; D001646:Bile / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011134:Polysaccharides / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D051381:Rats / Q000097:blood / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*
D011134:Polysaccharides; D014168:Transferrin