scholarly journals Imbalance of the Nerve Growth Factor and Its Precursor as a Potential Biomarker for Diabetic Retinopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
B. A. Mysona ◽  
S. Matragoon ◽  
M. Stephens ◽  
I. N. Mohamed ◽  
A. Farooq ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Experimental Diabetes ◽  
Critical Role ◽  
Diabetic Patients ◽  
Retinal Damage ◽  
Nerve Growth ◽  
Potential Biomarker ◽  
Early Biomarker

Our previous studies have demonstrated that diabetes-induced oxidative stress alters homeostasis of retinal nerve growth factor (NGF) resulting in accumulation of its precursor, proNGF, at the expense of NGF which plays a critical role in preserving neuronal and retinal function. This imbalance coincided with retinal damage in experimental diabetes. Here we test the hypothesis that alteration of proNGF and NGF levels observed in retina and vitreous will be mirrored in serum of diabetic patients. Blood and vitreous samples were collected from patients (diabetic and nondiabetic) undergoing vitrectomy at Georgia Regents University under approved IRB. Levels of proNGF, NGF, andp75NTRshedding were detected using Western blot analysis. MMP-7 activity was also assayed. Diabetes-induced proNGF expression and impaired NGF expression were observed in vitreous and serum. Vitreous and sera from diabetic patients(n=11)showed significant 40.8-fold and 3.6-fold increases, respectively, compared to nondiabetics(n=9). In contrast, vitreous and sera from diabetic patients showed significant 44% and 64% reductions in NGF levels, respectively, compared to nondiabetics. ProNGF to NGF ratios showed significant correlation between vitreous and serum. Further characterization of diabetes-induced imbalance in the proNGF to NGF ratio will facilitate its utility as an early biomarker for diabetic complications.

scholarly journals Critical Role for Kalirin in Nerve Growth Factor Signaling through TrkA

2005 ◽  
Vol 25 (12) ◽  
pp. 5106-5118 ◽  
Author(s):  
Kausik Chakrabarti ◽  
Rong Lin ◽  
Noraisha I. Schiller ◽  
Yanping Wang ◽  
David Koubi ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Critical Role ◽  
Neuronal Morphology ◽  
Neurotrophin Receptor ◽  
General Mechanism ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Nerve Growth

ABSTRACT Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low concentration of NGF. Furthermore, elevated Kalirin expression resulted in catalytic activation of TrkA, as demonstrated by in vitro kinase assays and increased NGF-stimulated cellular activation of Rac, Mek, and CREB. Domain mapping demonstrated that the N-terminal Kalirin pleckstrin homology domain mediates the interaction with TrkA. The effects of Kalirin on TrkA provide a molecular basis for the requirement of Kalirin in process extension from PC12 cells and for previously observed effects on axonal extension and dendritic maintenance. The interaction of TrkA with the pleckstrin homology domain of Kalirin may be one example of a general mechanism whereby receptor/Rho GEF pairings play an important role in receptor tyrosine kinase activation and signal transduction.

Characterization of the γ subunits of the 7S nerve growth factor complex

Biochemistry ◽  
1976 ◽  
Vol 15 (7) ◽  
pp. 1455-1461 ◽  
Author(s):  
Robert W. Stach ◽  
Alfred C. Server ◽  
Pier F. Pignatti ◽  
Arthur Piltch ◽  
Eric M. Shooter
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Nerve Growth

Increased nerve growth factor mRNA in lateral calf skin biopsies from diabetic patients

1999 ◽  
Vol 16 (2) ◽  
pp. 113-119 ◽  
Author(s):  
L. T. Diemel ◽  
F. Cai ◽  
P. Anand ◽  
G. Warner ◽  
P. G. Kopelman ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Diabetic Patients ◽  
Nerve Growth ◽  
Skin Biopsies ◽  
Calf Skin

The Characterization of the ?-Subunits of 7S Nerve Growth Factor

1980 ◽  
Vol 34 (4) ◽  
pp. 850-855 ◽  
Author(s):  
Robert W. Stach ◽  
Pier F. Pignatti ◽  
Michael E. Baker ◽  
Eric M. Shooter
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Nerve Growth
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