Characterization of a chicken hepatoma cell line with a specific defect in fibrinogen secretion.

Abstract

This study characterizes plasma protein synthesis and its hormonal regulation in a chicken hepatoma cell line, with particular emphasis on fibrinogen. Whereas virtually all aspects of hemopexin, transferrin and albumin production in these cells corresponded to those of cultured primary hepatocytes, fibrinogen was not secreted. Analysis of fibrinogen subunit synthesis revealed a specific defect in synthesis of one subunit, gamma, correlating with a lack of its mRNA. Pulse-chase and electron microscopic studies demonstrate that, despite the inability of these cells to secrete the A alpha and B beta subunits produced, there is no long-term accumulation of unsecreted fibrinogen. The B beta fibrinogen subunits are largely degraded 2 hr after synthesis. During this time, approximately half of the A alpha subunits are degraded; the rest are converted to the glycosylated form. The implications of this type of defect with respect to the pathogenesis of fibrinogen storage disease are discussed.