title: [Assembly and secretion of mutant fibrinogens with variant gamma-chain C terminal region (gamma313-gamma345)].
abstract: BACKGROUND
  It has been reported that the structure of the fibrinogen gamma-chain C terminal (D) region (140-411 residues) has important functions in fibrinogen assembly and/or secretion. Variant fibrinogens, gamma313S>N, gamma336M>I, gamma341A>D, and gamma345N>D have been reported as hypofibrinogenemias or dysfibrinogenemias. To study the assembly and secretion of the variant fibrinogens containing aberrant D regions, we established CHO cells producing these four fibrinogens.
  
  
  METHODS
  A fibrinogen gamma-chain expression vector was altered and transfected into CHO cells that expressed normal human fibrinogen Aalpha and Bbeta-chains. Cell lysates and culture media of the selected cell lines were subjected to ELISA and immunoblot analysis.
  
  
  RESULTS
  The CHO cells synthesized mutant gamma-chains and assembled these into fibrinogen, although these variant fibrinogens were barely secreted into the culture media. In the cell lysates, however, concentrations of these variant fibrinogens were higher than the normal levels.
  
  
  CONCLUSIONS
  The present study indicated that the tertiary structure of the fibrinogen gamma-chain C terminal region between 313 and 345 is necessary for fibrinogen secretion. These findings suggest that reduced levels of fibrinogen secretion lead to the hypofibrinogen in the patients and secreted fibrinogens might show dysfibrinogenemia.
authors.affiliation: Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University, Matsumoto 390-8621, Japan. fterasa@shinshu-u.ac.jp
authors.forename: Fumiko
authors.initials: F
authors.lastname: Terasawa
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kamijyo
authors.forename: Noriko
authors.initials: N
authors.lastname: Fujihara
authors.forename: Nobuo
authors.initials: N
authors.lastname: Okumura
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D015241:Fibrinogens, Abnormal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D009154:Mutation; D010957:Plasmids
chemical_list: D015241:Fibrinogens, Abnormal