Recombinant variant fibrinogens substituted at residues γ326Cys and γ339Cys demonstrated markedly impaired secretion of assembled fibrinogen

The present study indicated that the 326-339 intrachain disulfide bond has a crucial role in maintaining the tertiary structure of the C-terminal domain of the γ-module, which is necessary for fibrinogen assembly and secretion

Ayumi Haneishi

2009

Scholarcy highlights

  • Fibrinogen is a 340 kDa plasma glycoprotein composed of two sets of three different polypeptide chains, Aα, Bβ, and γ, which are stabilized by 29 disulfide bonds, including 12 intrachain and 17 interchain disulfide connections
  • Four variant and normal fibrinogens were expressed in Chinese hamster ovary cells, and the cell lysates and culture media of 8 to 14 fibrinogen-synthesizing cell lines were selected as described in the Materials and Methods
  • For the media of γ326A cells, a weak variant fibrinogen band was observed at 6 h, but it became fainter at 8 h. These results indicated that the rates of both assembly and secretion for the γ326A variant fibrinogen were slower than those of normal fibrinogen
  • To examine the assembly and/or secretion of variant fibrinogens substituted at residues
  • It was first speculated that the variant fibrinogens were assembled at a similar rate to normal fibrinogen in the cells but had a reduced rate of secretion into the culture media
  • Experiments using CHO cells do not reflect the function of human hepatocytes properly in vivo; the present results concerning fibrinogen assembly and secretion are coincident with the observation of naturally occurring variant fibrinogens
  • Experiments using Chinese hamster ovary cells do not reflect the function of human hepatocytes properly in vivo; the present results concerning fibrinogen assembly and secretion are coincident with the observation of naturally occurring variant fibrinogens

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