Organ cultures of human fetal hepatocytes in the study of extra-and intracellular alpha1-antitrypsin.
The rate of synthesis of alpha 1-antitrypsin has been studied in organ cultures of fetal human liver. By de novo synthesis, alpha 1-antitrypsin of the same electrophoretic mobility and molecular size as plasma alpha 1-antitrypsin was produced. Synthetic rate was comparable to in vivo conditions and was suppressed by cycloheximide, colchicine and neuraminidase. By increasing alpha 1-antitrypsin levels in cultre medium, suppression of alpha 1-antitrypsin release from the intra-to the extracellular site was achieved, i.e., synthesis does not proceed autonomously. This suppression was preceded by a temporary enhancement of synthesis. Both effects were found to be independent of degree of sialylation of add-d alpha 1-antitrypsin. In contrast to alpha 1-antitrypsin released in tissue culture, the intracellular protein, as analyzed by crossed immunoelectrophoresis of Triton X-100 extracts from fetal liver, was found to occur partly as slowly moving peaks. Whether these peaks represent proforms or incompletely glycosylated precursors of export alpha 1-antitrypsin or complexes with proteases remains unsettled. A variety of other plasma proteins are released in organ cultures making the system suitable for study of factors regulating plasma protein synthesis.
D003470:Culture Media; D005110:Extracellular Space / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D009924:Organ Culture Techniques; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis / Q000378:metabolism*
D003470:Culture Media; D006023:Glycoproteins; D000515:alpha 1-Antitrypsin; D009439:Neuraminidase