Document Detail

The fusion of IGF I with stromal cell-derived factor I or alpha1 proteinase inhibitor alters their mitogenic or chemotactic activities while keeping their ability to inhibit HIV-1-gp120 binding.
MedLine Citation:
PMID:  12787886     Owner:  NLM     Status:  MEDLINE    
It has been previously reported that insulin-like growth factor I (IGF I) decreases in AIDS patients with wasting, a condition that is partially prevented by combined IGF I growth hormone therapy. By generating bifunctional proteins of IGF I and stromal cell-derived factor 1alpha (SDF-1alpha) or alpha1 proteinase inhibitor (API), two proteins known to prevent HIV infection, it may be possible to improve the therapeutic effectiveness of these compounds for the treatment of AIDS-mediated wasting. SDF-1alpha or the M351E-M358L mutant of API were attached at the C-terminal end of IGF I and synthesized by a stable insect cell expression technique. The IGF I-SDF-1alpha chimera reduced the enhancement of thymidine incorporation into bovine fetal erythroid cells observed in the presence of insect cell produced IGF I alone. It also decreased the SDF-1 and IGF I-stimulated hematopoietic cell migration, without losing the capacity to compete with the binding of HIV-1 (IIIB)-surface glycoprotein gp120. The IGF I-API chimera displayed the same mitogenic activity and a similar, but lower chemotactic activity than IGF I in the assays mentioned above. It had a comparable anti-elastase activity to that observed with a previously described IGF II-API fusion protein with the single mutation M351E. The binding of gp120 to a murine hematopoietic cell line was stimulated by human neutrophil elastase (25-100 nM) and inhibited by IGF I-API. In conclusion, the linkage of IGF I with SDF-1 or API can alter some biological functions of the single components of the chimera while keeping their ability to compete with HIV-1-gp120 binding.
Carolyn Sandoval; Angelina Stojanova; Marcos R DiFalco; L Fernando Congote
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  65     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-05     Completed Date:  2003-07-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2055-63     Citation Subset:  IM    
Endocrine Laboratory, McGill University Health Centre, 687 avenue des pins, ouest, Montreal, Que., Canada H3A 1A1.
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MeSH Terms
Amino Acid Sequence
Base Sequence
Binding, Competitive
Chemokine CXCL12
Chemokines, CXC / genetics,  metabolism*,  pharmacology
Chemotaxis / drug effects
HIV Envelope Protein gp120 / drug effects*
HIV-1 / chemistry
Hematopoietic Stem Cells / drug effects,  physiology
Insects / cytology
Insulin-Like Growth Factor I / genetics,  metabolism*,  pharmacology
Mitogens / pharmacology
Molecular Sequence Data
Recombinant Fusion Proteins / metabolism,  pharmacology
alpha 1-Antitrypsin / genetics,  metabolism*,  pharmacology
Reg. No./Substance:
0/CXCL12 protein, human; 0/Chemokine CXCL12; 0/Chemokines, CXC; 0/HIV Envelope Protein gp120; 0/Mitogens; 0/Recombinant Fusion Proteins; 0/alpha 1-Antitrypsin; 67763-96-6/Insulin-Like Growth Factor I

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