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Article

In vitro expression of mutant factor VII proteins and characterization of their clinical significance

  • Authors:
    • Amir Mashayekhi
    • Shirin Shahbazi
    • Mirdavood Omrani
    • Reza Mahdian
  • View Affiliations / Copyright

    Affiliations: Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 1431633443, Iran, Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran, Department of Molecular Medicine, Pasteur Institute of Iran, Tehran 1316943551, Iran
  • Pages: 2738-2742
    |
    Published online on: November 27, 2017
       https://doi.org/10.3892/mmr.2017.8158
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Abstract

Abstract. Factor VII (FVII) serves an essential role in the initiation of blood coagulation. Mutations in conserved residues within its serine protease domain may lead to dysregulated coagulation activity. The objective of the present study was to elucidate the impact of altering two conserved residues, H348R and S282R, on the functional properties of the FVII protein. The mutation‑harboring fragments were derived from genomic DNA of a FVII deficient patient. The fragments were integrated into a pcDNA vector containing FVII cDNA of HepG2 cells. The wild-type and mutated FVII constructs were transfected into CHO‑K1 cells as a mammalian cell model. The coagulation activity, antigen levels and intracellular localization of the recombinant proteins were studied in association with their pathological importance. Results indicated that FVII activity was not detectable in conditioned media of the cells transfected with the mutated constructs. The H348R mutation reduced the expression of intracellular and secreted forms of the FVII protein. Following S282R transfection, intracellular FVII expression showed no significant variation; however, extracellular protein was reduced. The pattern of intracellular localization of mutated FVII remained unaltered in comparison to the wild-type protein. In conclusion, the present study suggested that missense mutations within the serine protease domain of FVII affect extracellular levels in addition to the coagulation activity of FVII. These results may contribute to further understanding of the molecular pathogenesis of FVII deficiency and the development of pharmaceutical candidates with improved therapeutic properties.
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1 

Hellstern P, Beeck H, Fellhauer A, Fischer A and Faller-Stöckl B: Measurement of factor VII and of activated factor VII in healthy individuals and in prothrombin complex concentrates. Thromb Res. 86:493–504. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Millar DS, Kemball-Cook G, McVey JH, Tuddenham EG, Mumford AD, Attock GB, Reverter JC, Lanir N, Parapia LA, Reynaud J, et al: Molecular analysis of the genotype-phenotype relationship in factor VII deficiency. Hum Genet. 107:327–342. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Tanaka R, Nakashima D, Suzuki A, Miyawaki Y, Fujimori Y, Yamada T, Takagi A, Murate T, Yamamoto K, Katsumi A, et al: Impaired secretion of carboxyl-terminal truncated factor VII due to an F7 nonsense mutation associated with FVII deficiency. Thromb Res. 125:262–266. 2010. View Article : Google Scholar : PubMed/NCBI

4 

O'Hara PJ, Grant FJ, Haldeman BA, Gray CL, Insley MY, Hagen FS and Murray MJ: Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation. Proc Natl Acad Sci USA. 84:pp. 5158–5162. 1987; View Article : Google Scholar : PubMed/NCBI

5 

Nagaizumi K, Inaba H, Suzuki T, Hatta Y, Hagiwara T, Amano K, Arai M and Fukutake K: Two double heterozygous mutations in the F7 gene show different manifestations. Br J Haematol. 119:1052–1058. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Shahbazi S: Nonsense-mediated mRNA decay among coagulation factor genes. Iran J Basic Med Sci. 19:344–349. 2016.PubMed/NCBI

7 

Mariani G and Bernardi F: Factor VII deficiency. Semin Thromb Hemos. 35:400–406. 2009. View Article : Google Scholar

8 

Mariani G, Herrmann FH, Dolce A, Batorova A, Etro D, Peyvandi F, Wulff K, Schved JF, Auerswald G, Ingerslev J, et al: Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. Thromb Haemost. 93:481–487. 2005.PubMed/NCBI

9 

Liu N, Aldea S, Francois D, Cherqui-Michel M, Giansily-Blaizot M and Fischler M: Recombinant activated factor VII for a patient with factor VII deficiency undergoing urgent intracerebral haematoma evacuation with underlying cavernous angioma. Br J Anaesth. 103:858–860. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Ahmed RP, Biswas A, Kannan M, Bhattacharya M, Geisen C, Seifried E, Oldenburg J and Saxena R: First report of a FVII-deficient Indian patient carrying double heterozygous mutations in the FVII gene. Thromb Res. 115:535–536. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Peyvandi F, Jenkins PV, Mannucci PM, Billio A, Zeinali S, Perkins SJ and Perry DJ: Molecular characterisation and three-dimensional structural analysis of mutations in 21 unrelated families with inherited factor VII deficiency. Thromb Haemost. 84:250–257. 2000.PubMed/NCBI

12 

Ma W, Shi X, Lu S, Wu L and Wang Y: Hypoxia-induced overexpression of DEC1 is regulated by HIF-1α in hepatocellular carcinoma. Oncol Rep. 30:2957–2962. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Jiang P, Xue D, Zhang Y, Ye L, Liu Y, Makale M, Kesari S, Edgington TS and Liu C: The extrinsic coagulation cascade and tissue factor pathway inhibitor in macrophages: A potential therapeutic opportunity for atherosclerotic thrombosis. Thromb Res. 133:657–666. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Quintavalle G, Riccardi F, Rivolta GF, Martorana D, Di Perna C, Percesepe A and Tagliaferri A; Ad-Hoc Study Group, : F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency. Results from a genotype-phenotype study. Thromb Haemost. 117:1455–1464. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Girolami A, Cosi E, Ferrari S, Girolami B and Lombardi AM: Bleeding manifestations in heterozygotes with congenital FVII deficiency: A comparison with unaffected family members during a long observation period. Hematology. 22:375–379. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Hunault M, Arbini AA, Carew JA, Peyvandi F and Bauer KA: Characterization of two naturally occurring mutations in the second epidermal growth factor-like domain of factor VII. Blood. 93:1237–1244. 1999.PubMed/NCBI

17 

Branchini A, Ferrarese M, Lombardi S, Mari R, Bernardi F and Pinotti M: Differential functional readthrough over homozygous nonsense mutations contributes to the bleeding phenotype in coagulation factor VII deficiency. J Thromb Haemost. 14:1994–2000. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Hao X, Cheng X, Ye J, Wang Y, Yang L, Wang M and Jin Y: Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s. Blood Coagul Fibrinolysis. 27:461–463. 2016. View Article : Google Scholar : PubMed/NCBI

19 

D'Andrea G, Bossone A, Lupone MR, Peyvandi F, Maisto G, Perricone F, Grandone E and Margaglione M: Molecular characterization of a factor VII deficient patient supports the importance of the second epidermal growth factor-like domain. Haematologica. 89:979–984. 2004.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Mashayekhi A, Shahbazi S, Omrani M and Mahdian R: In vitro expression of mutant factor VII proteins and characterization of their clinical significance. Mol Med Rep 17: 2738-2742, 2018.
APA
Mashayekhi, A., Shahbazi, S., Omrani, M., & Mahdian, R. (2018). In vitro expression of mutant factor VII proteins and characterization of their clinical significance. Molecular Medicine Reports, 17, 2738-2742. https://doi.org/10.3892/mmr.2017.8158
MLA
Mashayekhi, A., Shahbazi, S., Omrani, M., Mahdian, R."In vitro expression of mutant factor VII proteins and characterization of their clinical significance". Molecular Medicine Reports 17.2 (2018): 2738-2742.
Chicago
Mashayekhi, A., Shahbazi, S., Omrani, M., Mahdian, R."In vitro expression of mutant factor VII proteins and characterization of their clinical significance". Molecular Medicine Reports 17, no. 2 (2018): 2738-2742. https://doi.org/10.3892/mmr.2017.8158
Copy and paste a formatted citation
x
Spandidos Publications style
Mashayekhi A, Shahbazi S, Omrani M and Mahdian R: In vitro expression of mutant factor VII proteins and characterization of their clinical significance. Mol Med Rep 17: 2738-2742, 2018.
APA
Mashayekhi, A., Shahbazi, S., Omrani, M., & Mahdian, R. (2018). In vitro expression of mutant factor VII proteins and characterization of their clinical significance. Molecular Medicine Reports, 17, 2738-2742. https://doi.org/10.3892/mmr.2017.8158
MLA
Mashayekhi, A., Shahbazi, S., Omrani, M., Mahdian, R."In vitro expression of mutant factor VII proteins and characterization of their clinical significance". Molecular Medicine Reports 17.2 (2018): 2738-2742.
Chicago
Mashayekhi, A., Shahbazi, S., Omrani, M., Mahdian, R."In vitro expression of mutant factor VII proteins and characterization of their clinical significance". Molecular Medicine Reports 17, no. 2 (2018): 2738-2742. https://doi.org/10.3892/mmr.2017.8158
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