Bioactivity of a 29-kilodalton insulin-like growth factor binding protein-3 fragment present in excess in chronic renal failure serum

Susan K. Durham, Subburaman Mohan, Frances Liu, Bonita K. Baker, Phillip D K Lee, Raymond L. Hintz, Cheryl A Conover, David R. Powell

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Abstract

Children with chronic renal failure (CRF) have normal or high serum levels of GH, IGF-I, and IGF-II. Despite this, the serum of CRF patients has low IGF bioactivity, which may contribute to CRF growth failure. Recent studies suggest that excess IGF binding proteins (IGFBPs) in the ~35-kD fractions of CRF serum contribute to this low IGF bioactivity. This report characterizes a 29-kD form of IGFBP-3, IGFBP-329, which accumulates in the ~35-kD fractions of CRF serum and peritoneal dialysate. Deglycosylation and [125I]IGF ligand blot studies show that IGFBP-329 is a glycosylated IGFBP-3 fragment with low affinity for IGF peptides. Using an IGFBP-3 antibody column, IGFBP-329 was purified to homogeneity from the ~35-kD fractions of peritoneal dialysate from children with CRF. Compared with native IGFBP-3, pure IGFBP-329 has a 4-10-fold lower affinity for IGP-II and a 200-fold lower affinity for IGF-I. Consistent with the binding data, IGFBP-329 inhibited IGF-II stimulated thymidine incorporation in chondrosarcoma cells, but was a less potent inhibitor than native IGFBP-3; also, native IGFBP-3 clearly inhibited IGF-I-stimulated thymidine incorporation in chondrosarcoma cells and potentiated IGF-I-stimulated aminoisobutyric acid uptake in bovine fibroblasts, but higher concentrations of IGFBP-329 had no effect on these IGF-I actions. Thus, the 29-kD IGFBP-3 form that accumulates in CRF serum and extravascular spaces is an IGFBP-3 fragment that may modulate IGF-II, but not IGF-I, effects on target tissues. Whether IGFBP-329 plays any role in the growth failure of children with CRF remains to be determined.

Original languageEnglish (US)
Pages (from-to)335-341
Number of pages7
JournalPediatric Research
Volume42
Issue number3
StatePublished - Sep 1997

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Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor Binding Protein 3
Chronic Kidney Failure
Insulin-Like Growth Factor I
Serum
Insulin-Like Growth Factor II
Chondrosarcoma
Dialysis Solutions
Thymidine
Aminoisobutyric Acids
Growth
Fibroblasts
Ligands
Peptides
Antibodies

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Durham, S. K., Mohan, S., Liu, F., Baker, B. K., Lee, P. D. K., Hintz, R. L., ... Powell, D. R. (1997). Bioactivity of a 29-kilodalton insulin-like growth factor binding protein-3 fragment present in excess in chronic renal failure serum. Pediatric Research, 42(3), 335-341.

Bioactivity of a 29-kilodalton insulin-like growth factor binding protein-3 fragment present in excess in chronic renal failure serum. / Durham, Susan K.; Mohan, Subburaman; Liu, Frances; Baker, Bonita K.; Lee, Phillip D K; Hintz, Raymond L.; Conover, Cheryl A; Powell, David R.

In: Pediatric Research, Vol. 42, No. 3, 09.1997, p. 335-341.

Research output: Contribution to journalArticle

Durham, SK, Mohan, S, Liu, F, Baker, BK, Lee, PDK, Hintz, RL, Conover, CA & Powell, DR 1997, 'Bioactivity of a 29-kilodalton insulin-like growth factor binding protein-3 fragment present in excess in chronic renal failure serum', Pediatric Research, vol. 42, no. 3, pp. 335-341.
Durham, Susan K. ; Mohan, Subburaman ; Liu, Frances ; Baker, Bonita K. ; Lee, Phillip D K ; Hintz, Raymond L. ; Conover, Cheryl A ; Powell, David R. / Bioactivity of a 29-kilodalton insulin-like growth factor binding protein-3 fragment present in excess in chronic renal failure serum. In: Pediatric Research. 1997 ; Vol. 42, No. 3. pp. 335-341.
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AU - Lee, Phillip D K

AU - Hintz, Raymond L.

AU - Conover, Cheryl A

AU - Powell, David R.

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