The insulin-like growth factor system in the circulation of patients with viral infections

2004 ◽  
Vol 42 (10) ◽  
Author(s):  
Ivona Baričević ◽  
Olgica Nedić ◽  
Judith Anna Nikolić ◽  
Jasminka Nedeljković
Keyword(s):  
Growth Factor ◽  
Viral Infections ◽  
Serum Cortisol ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Ligand Affinity ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Simplex Virus

AbstractThe insulin-like growth factor (IGF) system was examined in the circulation of patients with viral infections (herpes simplex virus, HSV; cytomegalovirus, CMV; rotavirus, RV and adenovirus, AV). The serum concentrations of IGF-I, IGF-II and cortisol were measured by radioimmunoassay, while IGF-binding proteins (IGFBPs) were characterised by ligand-affinity blotting. Although both IGF-I and IGF-II concentrations were significantly lower in patients with viral infections (p < 0.05) than in healthy persons, the IGF-II/IGF-I ratio was increased (p < 0.05). No correlation between the concentration of IGF-I and IGF-II and the intensity of the antibody response to infection was observed. Ligand-affinity blotting demonstrated decreased amounts of IGFBP-3 (patients with HSV, CMV, AV and some patients with RV), increased IGFBP-2 (some patients with HSV and RV) and IGFBP-1 (patients with RV). Serum cortisol was significantly elevated (p < 0.05) in patients infected with HSV, CMV and RV. The alterations observed can be interpreted as induction of the hypothalamic-pituitary-adrenal axis and suppression of the growth hormone (GH)/IGF axis under the influence of viral infection.

scholarly journals Mutations in the B-domain of insulin-like growth factor-I influence the oxidative folding to yield products with modified biological properties

1995 ◽  
Vol 308 (3) ◽  
pp. 865-871 ◽  
Author(s):  
S J Milner ◽  
G L Francis ◽  
J C Wallace ◽  
B A Magee ◽  
F J Ballard
Keyword(s):  
Growth Factor ◽  
Biological Properties ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Oxidative Folding ◽  
Biological Assays ◽  
Igf I ◽  
Igf Binding ◽  
L6 Myoblast

The oxidative folding of human insulin-like growth factor (IGF)-I yields two major disulphide folding isomers. In the present study, B-domain analogues of IGF-I were used to investigate the effect of mutations on the folding reaction and to investigate the functional implications of misfolding. The analogues used were substitutions of the native Glu3 by Gly or Arg, or the native Glu9 by Lys. IGF-I and these analogues were also prepared attached to a hydrophobic 13-amino-acid N-terminal extension, Met-Phe-Pro-Ala-Met-Pro-Leu-Ser-Ser-Leu-Phe-Val-Asn, referred to as ‘Long-IGF-I’ analogues. Each IGF was fully reduced and refolded to yield native and misfolded isomers, which were subsequently purified for biological characterization. Analysis of the folding reaction at equilibrium revealed a distribution of folding isomers characteristic for each peptide. The yield of the native disulphide folding isomer was increased for the Glu3 substitutions, but not for the Glu9 substitution. The main alternative folding isomer was present in the IGF-I analogues in reduced proportions. Except for [Gly3]IGF-I the N-terminal extension increased the yield of the native isomer which was maximal for the analogue Long-[Arg3]IGF-I. A folding intermediate for the latter analogue was isolated and partially characterized. The biological assays showed that all the main alternative isomers bound poorly to IGF-binding proteins (IGFBPs) secreted by L6 myoblasts. Moreover, these isomers bound to the type 1 IGF receptor with 0.5-25% the affinity of the native isomer. In a rat L6 myoblast protein-synthesis assay, the observed biological activity of the native and main alternative isomers was explained by their modified IGFBP- and receptor-binding properties. We propose that the N-terminal extension imparts a steric constraint at a crucial point in folding, thus allowing native disulphide bonds to form efficiently.

scholarly journals Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-6 in IGF-II

1993 ◽  
Vol 293 (3) ◽  
pp. 713-719 ◽  
Author(s):  
G L Francis ◽  
S E Aplin ◽  
S J Milner ◽  
K A McNeil ◽  
F J Ballard ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Biological Activities ◽  
Biological Properties ◽  
Hepatoma Cells ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Anabolic Response ◽  
Igf I ◽  
Igf Binding

Recombinant insulin-like growth factor-II (IGF-II) and two structural analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were produced to investigate the role of N-terminal residues in binding to IGF-binding proteins (IGFBPs) and hence the biological properties of the modified peptides. The growth factors were modelled on two previously characterized variants of IGF-I, des(1-3)IGF-I and [Arg3]-IGF-I, which both show substantially decreased binding to IGFBPs and were expressed as fusion proteins in Escherichia coli. The biological activities of the corresponding analogues of IGF-I and IGF-II were compared in rat L6 myoblasts and H35B hepatoma cells. In the L6-myoblast protein-synthesis assay, the IGF-II analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were slightly more potent than IGF-II but about 10-fold less potent than IGF-I and 100-fold less potent than the respective IGF-I analogues, des(1-3)IGF-I and [Arg3]IGF-I. In H35 hepatoma cells the anabolic response measured was the inhibition of protein breakdown, and the potency order was insulin >>> [Arg3]-IGF-I > des(1-3)IGF-I > [Arg6]-IGF-II > des(1-6)IGF-II > IGF-I > IGF-II. Binding of the IGFs and their analogues to the type 1 IGF receptor in L6 myoblasts and to the insulin receptor in H35 hepatoma cells did not fully explain the observed anabolic potency differences. Moreover, binding of all four analogues to the IGFBPs secreted by L6 myoblasts and H35B hepatoma cells was greatly decreased compared with the parent IGF. We conclude that the observed anabolic response to each IGF was determined by their relative binding to the competing cell receptor and IGFBP binding sites present.

IGF-binding protein-2 is induced during development of urinary bladder hypertrophy in the diabetic rat

1997 ◽  
Vol 272 (2) ◽  
pp. E297-E303 ◽  
Author(s):  
Y. Chen ◽  
B. Gustafsson ◽  
H. J. Arnqvist
Keyword(s):  
Growth Factor ◽  
Urinary Bladder ◽  
Messenger Rna ◽  
Diabetic Rat ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Streptozotocin Induced Diabetes ◽  
Wet Weight

Because the locally produced insulin-like growth factor-binding proteins (IGFBP) may influence bladder hypertrophy, either directly or by their interaction with insulin-like growth factor I (IGF-I), we studied the IGF system during the development of urinary bladder hypertrophy in rats with streptozotocin-induced diabetes. Messenger RNA for IGF-I, IGFBP-2, and IGFBP-4 was determined by solution hybridization. The bladder wet weight was elevated after 7 days. DNA synthesis was increased and peaked at 2 days, whereas DNA content per bladder wet weight was decreased by 7 days. The IGF-I mRNA did not change during the first 7 days and then decreased, and IGFBP-4 mRNA was increased transiently on day 7. On the other hand, IGFBP-2 mRNA was significantly increased after 1 day (2-fold), peaked by 7 days (6.4-fold), and then declined to approximately 50% above control at the end of experiment. This was associated with an increased IGFBP-2 protein content. Our results suggest that both stretching of the bladder due to diuresis and the diabetic state contribute to changes of the IGF system in the hypertrophying bladder.

Ontogenic Changes in the Circulating Concentrations of Insulin-like Growth Factor (IGF)-I, IGF-II, and IGF-Binding Proteins in the Chicken Embryo

1997 ◽  
Vol 106 (2) ◽  
pp. 265-270 ◽  
Author(s):  
Colin G. Scanes ◽  
Robert C. Thommes ◽  
Steven V. Radecki ◽  
Frances C. Buonomo ◽  
James E. Woods
Keyword(s):  
Growth Factor ◽  
Chicken Embryo ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding
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