Abstract
IGF-binding protein-3 (IGFBP-3), usually found as glycosylated 41- and 38- kD forms, is the major serum IGFBP during extrauterine life. In normal serum IGFBP-3 binds one IGF peptide and one acid-labile (α) subunit in a high- molecular-weight (MW) complex of 150 kD. By RIA, an excess of IGFBP-3 is present in chronic renal failure (CRF) serum, where it reportedly accumulates at low MW (25-55 kD) rather than as part of the 150-kD complex. To further evaluate IGFBP-3 forms in CRF, sera were obtained from seven healthy adolescents and seven adolescents with CRF. By RIA, IGFBP-3 levels were higher in CRF than normal sera (15.4 ± 2.2 versus 10.1 ± 2.1 μg/mL). High- MW (150-kD) fractions of CRF and normal sera, obtained by neutral size- exclusion chromatography, had equal amounts of IGFBP-3 by RIA. However, a second RIA peak of IGFBP-3, present in low-MW (35-kD) fractions of CRF but not normal sera, could account for the higher IGFBP-3 levels of CRF serum. [125I]IGF ligand blots of whole serum and serum fractions, either with or without prior precipitation by IGFBP-3 antiserum, found levels of 41- and 38- kD IGFBP-3 forms to be similar between CRF and normal whole sera and located these forms in the high-MW (150-kD) fractions of CRF and normal sera. [125I]IGF ligand blots also identified excess IGFBP in low-MW CRF serum fractions; cross-linking these IGFBP with [125I]IGF-I, followed by precipitation with IGFBP-1, -2, and -3 antibodies, identified high levels of unsaturated IGFBP-1, IGFBP-2, and 19- and 14-kD forms of IGFBP-3 in CRF serum. These studies indicate that 1) normal levels of functional 41- and 38- kD IGFBP-3 forms are present in CRF serum, and these forms can be incorporated into the 150-kD serum complex; and 2) high RIA levels of IGFBP- 3 in low-MW fractions of CRF serum are at least in part due to 19- and 14-kD IGFBP-3 forms. These studies suggest that the excess unsaturated IGFBP of CRF serum are small enough to enter interstitial tissue spaces where they may modulate IGF-I-mediated mitogenic, metabolic, and differentiative effects.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 136-143 |
| Number of pages | 8 |
| Journal | Pediatric Research |
| Volume | 33 |
| Issue number | 2 |
| State | Published - 1993 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
Cite this
Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum. / Powell, D. R.; Liu, F.; Baker, B.; Lee, Phillip; Belsha, C. W.; Brewer, E. D.; Hintz, R. L.
In: Pediatric Research, Vol. 33, No. 2, 1993, p. 136-143.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum
AU - Powell, D. R.
AU - Liu, F.
AU - Baker, B.
AU - Lee, Phillip
AU - Belsha, C. W.
AU - Brewer, E. D.
AU - Hintz, R. L.
PY - 1993
Y1 - 1993
N2 - IGF-binding protein-3 (IGFBP-3), usually found as glycosylated 41- and 38- kD forms, is the major serum IGFBP during extrauterine life. In normal serum IGFBP-3 binds one IGF peptide and one acid-labile (α) subunit in a high- molecular-weight (MW) complex of 150 kD. By RIA, an excess of IGFBP-3 is present in chronic renal failure (CRF) serum, where it reportedly accumulates at low MW (25-55 kD) rather than as part of the 150-kD complex. To further evaluate IGFBP-3 forms in CRF, sera were obtained from seven healthy adolescents and seven adolescents with CRF. By RIA, IGFBP-3 levels were higher in CRF than normal sera (15.4 ± 2.2 versus 10.1 ± 2.1 μg/mL). High- MW (150-kD) fractions of CRF and normal sera, obtained by neutral size- exclusion chromatography, had equal amounts of IGFBP-3 by RIA. However, a second RIA peak of IGFBP-3, present in low-MW (35-kD) fractions of CRF but not normal sera, could account for the higher IGFBP-3 levels of CRF serum. [125I]IGF ligand blots of whole serum and serum fractions, either with or without prior precipitation by IGFBP-3 antiserum, found levels of 41- and 38- kD IGFBP-3 forms to be similar between CRF and normal whole sera and located these forms in the high-MW (150-kD) fractions of CRF and normal sera. [125I]IGF ligand blots also identified excess IGFBP in low-MW CRF serum fractions; cross-linking these IGFBP with [125I]IGF-I, followed by precipitation with IGFBP-1, -2, and -3 antibodies, identified high levels of unsaturated IGFBP-1, IGFBP-2, and 19- and 14-kD forms of IGFBP-3 in CRF serum. These studies indicate that 1) normal levels of functional 41- and 38- kD IGFBP-3 forms are present in CRF serum, and these forms can be incorporated into the 150-kD serum complex; and 2) high RIA levels of IGFBP- 3 in low-MW fractions of CRF serum are at least in part due to 19- and 14-kD IGFBP-3 forms. These studies suggest that the excess unsaturated IGFBP of CRF serum are small enough to enter interstitial tissue spaces where they may modulate IGF-I-mediated mitogenic, metabolic, and differentiative effects.
AB - IGF-binding protein-3 (IGFBP-3), usually found as glycosylated 41- and 38- kD forms, is the major serum IGFBP during extrauterine life. In normal serum IGFBP-3 binds one IGF peptide and one acid-labile (α) subunit in a high- molecular-weight (MW) complex of 150 kD. By RIA, an excess of IGFBP-3 is present in chronic renal failure (CRF) serum, where it reportedly accumulates at low MW (25-55 kD) rather than as part of the 150-kD complex. To further evaluate IGFBP-3 forms in CRF, sera were obtained from seven healthy adolescents and seven adolescents with CRF. By RIA, IGFBP-3 levels were higher in CRF than normal sera (15.4 ± 2.2 versus 10.1 ± 2.1 μg/mL). High- MW (150-kD) fractions of CRF and normal sera, obtained by neutral size- exclusion chromatography, had equal amounts of IGFBP-3 by RIA. However, a second RIA peak of IGFBP-3, present in low-MW (35-kD) fractions of CRF but not normal sera, could account for the higher IGFBP-3 levels of CRF serum. [125I]IGF ligand blots of whole serum and serum fractions, either with or without prior precipitation by IGFBP-3 antiserum, found levels of 41- and 38- kD IGFBP-3 forms to be similar between CRF and normal whole sera and located these forms in the high-MW (150-kD) fractions of CRF and normal sera. [125I]IGF ligand blots also identified excess IGFBP in low-MW CRF serum fractions; cross-linking these IGFBP with [125I]IGF-I, followed by precipitation with IGFBP-1, -2, and -3 antibodies, identified high levels of unsaturated IGFBP-1, IGFBP-2, and 19- and 14-kD forms of IGFBP-3 in CRF serum. These studies indicate that 1) normal levels of functional 41- and 38- kD IGFBP-3 forms are present in CRF serum, and these forms can be incorporated into the 150-kD serum complex; and 2) high RIA levels of IGFBP- 3 in low-MW fractions of CRF serum are at least in part due to 19- and 14-kD IGFBP-3 forms. These studies suggest that the excess unsaturated IGFBP of CRF serum are small enough to enter interstitial tissue spaces where they may modulate IGF-I-mediated mitogenic, metabolic, and differentiative effects.
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M3 - Article
VL - 33
SP - 136
EP - 143
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 2
ER -