Biosynthesis of Abnormally Glycosylated α-Antitrypsin by a Human Hepatoma Cell Line†

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Abstract
The human hepatoma cell line PLC/PRF/5 synthesized and secreted a functioal α-antitrypsin (α-AT) glycoprotein with normal molecular size but retarded electrophoretic mobility. The total process of translation, glycosylation and export required about 40 min and followed the same synthetic pattern as seen in rat hepatocytes, i.e., a signal peptide is cleaved cotranslationally; a core-glycosylated protein in the high-mannose form is formed in the rough endoplasmic reticulum, trimmed, and a stable complex-glycosylated α 1-AT is found intracellularly prior to export. α 1-AT export to medium was delayed by tunicamycin, inhibited by cycloheximide but unaffected by colchicine. After addition of exogenous α 1-AT to culture medium, neither negative nor positive feedback induction of synthesis could be demonstrated. Electrophoretic techniques indicated the presence of atypical, highly branched but incompletely sialylated carbohydrate chains in the hepatoma cell-derived α 1-AT. The accumulation of intracellular α 1-AT inclusions seen in the endoplasmic reticulum may reflect an imbalance between a high rate of polypeptide synthesis and terminal glycosylation.
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