PMID- 10226801
OWN - NLM
STAT- MEDLINE
DCOM- 19990622
LR  - 20090219
IS  - 0018-5043 (Print)
IS  - 0018-5043 (Linking)
VI  - 31
IP  - 2-3
DP  - 1999 Feb-Mar
TI  - Proteolysis of insulin-like growth factor binding protein-3 in serum from 
      pregnant, non-pregnant and fetal rats by matrix metalloproteinases and serine 
      proteases.
PG  - 186-91
AB  - The insulin-like growth factors (IGFs) in adult mammalian plasma circulate 
      predominantly in 150-kDa complexes that also contain IGF-binding protein-3 
      (IGFBP-3) and an acid-labile subunit. Proteolysis of IGFBP-3 within the 150-kDa 
      complex decreases its affinity for IGFs, facilitating their release to the 
      tissues. By contrast, 150-kDa complexes are not detected in serum from fetal or 
      pregnant adult rats. Decreased complex formation results from insufficient 
      availability of IGFBP-3 due to increased IGFBP-3 proteolysis. The present study 
      characterizes IGFBP-3 protease activity in serum from fetal, pregnant and 
      non-pregnant adult rats by comparing the effect of different protease inhibitors. 
      Proteolysis of exogenous recombinant human IGFBP-3 (for fetal and pregnancy 
      serum) or endogenous IGFBP-3 (for non-pregnant adult rat serum) following 
      incubation at 37 degrees C was measured by ligand blotting. In all three sera, 
      IGFBP-3 proteolysis was inhibited completely by: (i) EDTA, a chelator of divalent 
      cations. Inhibition was reversed by zinc, but not by calcium ions; (ii) 
      4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), an inhibitor of serine 
      proteases; and (iii) a specific tissue inhibitor of matrix metalloproteinases 
      (TIMP-1). Recombinant human matrix metalloproteinase-3 (MMP-3) proteolyzed 
      recombinant human IGFBP-3 or endogenous rat IGFBP-3 in non-pregnancy serum 
      pretreated with AEBSF to inactivate endogenous serine proteases. These results 
      suggest that serine proteases initiate the activation of latent MMP precursor, 
      and that the activated MMP directly degrades IGFBP-3.
FAU - Wu, H B
AU  - Wu HB
AD  - Growth and Development Section, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 
      hbwu@nih.gov
FAU - Lee, C Y
AU  - Lee CY
FAU - Rechler, M M
AU  - Rechler MM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Germany
TA  - Horm Metab Res
JT  - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et 
      metabolisme
JID - 0177722
RN  - 0 (Carrier Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Somatomedins)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (alpha-Macroglobulins)
RN  - 0 (insulin-like growth factor binding protein, acid labile subunit)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Carrier Proteins/blood
MH  - Cricetinae
MH  - Enzyme Activation/physiology
MH  - Female
MH  - Glycoproteins/blood
MH  - Glycosylation
MH  - Insulin-Like Growth Factor Binding Protein 3/*blood
MH  - Matrix Metalloproteinase 3/*blood
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/metabolism
MH  - Serine Endopeptidases/*blood
MH  - Somatomedins/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/*blood
MH  - alpha-Macroglobulins/metabolism
EDAT- 1999/05/05 00:00
MHDA- 1999/05/05 00:01
CRDT- 1999/05/05 00:00
PHST- 1999/05/05 00:00 [pubmed]
PHST- 1999/05/05 00:01 [medline]
PHST- 1999/05/05 00:00 [entrez]
AID - 10.1055/s-2007-978718 [doi]
PST - ppublish
SO  - Horm Metab Res. 1999 Feb-Mar;31(2-3):186-91. doi: 10.1055/s-2007-978718.