Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum

D. R. Powell, F. Liu, B. Baker, Phillip Lee, C. W. Belsha, E. D. Brewer, R. L. Hintz

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)136-143
Number of pages8
JournalPediatric Research
Volume33
Issue number2
StatePublished - 1993
Externally publishedYes

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Insulin-Like Growth Factor Binding Protein 3
Chronic Kidney Failure
Serum
Molecular Weight
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor I
Ligands

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Powell, D. R., Liu, F., Baker, B., Lee, P., Belsha, C. W., Brewer, E. D., & Hintz, R. L. (1993). Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum. Pediatric Research, 33(2), 136-143.

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 journalArticle

Powell, DR, Liu, F, Baker, B, Lee, P, Belsha, CW, Brewer, ED & Hintz, RL 1993, 'Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum', Pediatric Research, vol. 33, no. 2, pp. 136-143.
Powell, D. R. ; Liu, F. ; Baker, B. ; Lee, Phillip ; Belsha, C. W. ; Brewer, E. D. ; Hintz, R. L. / Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum. In: Pediatric Research. 1993 ; Vol. 33, No. 2. pp. 136-143.
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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.",
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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.

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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.

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