ISSN Print: 2472-9574  ISSN Online: 2472-9590
International Journal of Chemical and Biomedical Science  
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The Construction of a Novel Fusion Protein GSH-bFGF and the Characterization of Its Activities in vitro
International Journal of Chemical and Biomedical Science
Vol.2 , No. 2, Publication Date: Aug. 18, 2016, Page: 9-16
2281 Views Since August 18, 2016, 837 Downloads Since Aug. 18, 2016
 
 
Authors
 
[1]    

Lin Chen, Department of Biology, School of Life Science and Technology, Jinan University, Guangzhou, China.

[2]    

Yi Zou, Department of Biology, School of Life Science and Technology, Jinan University, Guangzhou, China.

[3]    

Tianhong Zhou, Department of Biology, School of Life Science and Technology, Jinan University, Guangzhou, China.

[4]    

Hongjian Li, Department of Biology, School of Life Science and Technology, Jinan University, Guangzhou, China.

[5]    

Lin Cao, Department of Anesthesiology of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

 
Abstract
 

The basic fibroblast growth factor (bFGF) and glutathione (GSH) have extensive biological functions. The bFGF is currently used to treat cardiovascular diseases, osteoarthritis, chronic kidney disease, Parkinson’s disease and mood disorders due to its mitogenic activity. Also, GSH deficiency has been linked to a number of human diseases such as liver cirrhosis, pancreatic inflammation, diabetes, neurodegenerative diseases, pulmonary diseases and aging. In this study, we construct a novel fusion protein, glutathione-basic fibroblast growth factor (GSH-bFGF) and characterized its bio-activities in vitro. The results showed that GSH-bFGF promoted the proliferation of cultured NIH/3T3 and primary human umbilical vein endothelial cells (HUVECs) using CCK-8 assays. The fusion protein also displayed well preserved antioxidant activity using Total Antioxidant Capacity Assay and significantly inhibited the senescence of HUVECs. We therefore, proposed that comparing with GSH or bFGF alone, the synthetic novel fusion protein GSH-bFGF was likely to have improved potentials in treating aging related diseases, such as atherosclerosis and neurodegenerative diseases.


Keywords
 

GSH-bFGF, Proliferation, Antioxidant Ability, Cell Senescence, Atherosclerosis


Reference
 
[01]    

Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth [J]. Nature, 1974, 249: 123-127.

[02]    

Acevedo V D, Ittmann M, Spencer D M. Paths of FGFR-driven tumorigenesis [J]. Cell Cycle, 2009, 8 (4): 580-588.

[03]    

Maciag T, Mehlman T, Friesel R, et al. Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain [J]. Science, 1984, 225 (4665): 932-935.

[04]    

Shing Y, Folkman J, Sullivan R, et al. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor [J]. Science, 1984, 223 (4642): 1296-1299.

[05]    

Prats H, Kaghad M, Prats A C, et al. High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons [J]. Pro Natl Acad Sci, 1989, 86 (6): 1836-1840.

[06]    

Bikfalvi A, Klein S, Pintucci G, et al. Biological Roles of Fibroblast Growth Factor-2 1 [J]. Endocr Rev, 1997, 18 (1): 26-45.

[07]    

Mohammadi M, Olsen S K, Ibrahimi O A. Structural basis for fibroblast growth factor receptor activation [J]. Cytokine Growth F R, 2005, 16 (2): 107-137.

[08]    

Yun Y R, Won J E, Jeon E, et al. Fibroblast growth factors: biology, function, and application for tissue regeneration [J]. J Tissue Engineering, 2010, 1 (1): 218142.

[09]    

Johnson D E, Lu J, Chen H, et al. The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain [J]. Mol Cell Biol, 1991, 11 (9): 4627-4634.

[10]    

Schlessinger J, Plotnikov A N, Ibrahimi O A, et al. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization [J]. Mol Cell, 2000, 6 (3): 743-750.

[11]    

Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy [J]. Nat Rev Drug Discov, 2009, 8 (3): 235-253.

[12]    

Sternberg P W, Alberola-Ila J. Conspiracy theory: RAS and RAF do not act alone [J]. Cell, 1998, 95 (4): 447-450.

[13]    

Dailey L, Ambrosetti D, Mansukhani A, et al. Mechanisms underlying differential responses to FGF signaling [J]. Cytokine Growth F R, 2005, 16 (2): 233-247.

[14]    

Coutu D L, Galipeau J. Roles of FGF signaling in stem cell self-renewal, senescence and aging [J]. Aging (Albany NY), 2011, 3 (10): 920-33.

[15]    

Jin K, Sun Y, Xie L, et al. Neurogenesis and aging: FGF-2 and HB‐EGF restore neurogenesis in hippocampus and subventricular zone of aged mice [J]. Aging cell, 2003, 2 (3): 175-183.

[16]    

Penninckx M J, Elskens M T. Metabolism and functions of glutathione in micro-organisms [J]. Adv Microb Physiol, 1993, 34: 239-301.

[17]    

Ghezzi P. Protein glutathionylation in health and disease [J]. BBBA Gen Subjects, 2013, 1830 (5): 3165-3172.

[18]    

Meister A, Anderson M E. Glutathione [J]. Annu Rev Biochem, 1983, 52 (1): 711-760.

[19]    

Wu G, Fang Y Z, Yang S, et al. Glutathione metabolism and its implications for health [J]. J Nutr, 2004, 134 (3): 489-492.

[20]    

Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature, 1993, 801-809.

[21]    

Fridlyanskaya I, Alekseenko L, Nikolsky N. Senescence as a general cellular response to stress: A mini-review [J]. Exp Gerontol, 2015, 72: 124-128.

[22]    

Suzuki T, Akasaka Y, Namiki A, et al. Basic fibroblast growth factor inhibits ventricular remodeling in Dahl salt-sensitive hypertensive rats [J]. J Hypertens, 2008, 26 (12): 2436-2444.

[23]    

Tomanek R J, Zheng W, Yue X. Growth factor activation in myocardial vascularization: therapeutic implications [J]. Mol Cell Biochem, 2004, 264 (1-2): 3-11.

[24]    

Kanazawa T, Komazawa D, Indo K, et al. Single injection of basic fibroblast growth factor to treat severe vocal fold lesions and vocal fold paralysis [J]. The Laryngoscope, 2015, 125 (10): E338-E344.

[25]    

Liu Y, Yi X C, Guo G, et al. Basic fibroblast growth factor increases the transplantation mediated therapeutic effect of bone mesenchymal stem cells following traumatic brain injury [J]. Mol Med Rep, 2014, 9 (1): 333-339..

[26]    

Colavitti R, Finkel T. Reactive oxygen species as mediators of cellular senescence [J]. IUBMB life, 2005, 57 (4-5): 277-281.

[27]    

Homma T, Fujii J. Application of Glutathione as Anti-Oxidative and Anti-Aging Drugs [J]. Curr Drug Metab, 2015, 16 (7): 560-571.

[28]    

Nakamizo S, Egawa G, Natsuaki Y, et al. Topical treatment with basic fibroblast growth factor promotes wound healing and barrier recovery induced by skin abrasion [J]. Skin Pharmacol Physiol, 2013, 26 (1): 22-29.

[29]    

Webley K, Bond J A, Jones C J, et al. Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage [J]. Mol Cell Biol, 2000, 20 (8): 2803-2808.





 
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