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 Lee, Raymond L. Hintz, Cheryl A. Conover, David R. Powell

Research output: Contribution to journalArticle

27 Citations (Scopus)

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
Externally publishedYes

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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., 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; 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, P, 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 ; 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

AU - Hintz, Raymond L.

AU - Conover, Cheryl A.

AU - Powell, David R.

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