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    
Abstract/OtherAbstract:
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.
Authors:
Carolyn Sandoval; Angelina Stojanova; Marcos R DiFalco; L Fernando Congote
Related Documents :
3360216 - Autoradiographic evidence for insulin and insulin-like growth factor binding to early m...
1695626 - Discrete alterations of the insulin-like growth factor i molecule which alter its affin...
15543566 - Insulin-like growth factors in patients with liver cysts.
8448166 - Ligand binding by a recombinant insect juvenile hormone binding protein.
9694876 - Grb2 forms an inducible protein complex with cd28 through a src homology 3 domain-proli...
23277586 - Involvement of distinct arrestin-1 elements in binding to different functional forms of...
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    
Affiliation:
Endocrine Laboratory, McGill University Health Centre, 687 avenue des pins, ouest, Montreal, Que., Canada H3A 1A1.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Base Sequence
Binding, Competitive
Cattle
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
Humans
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
Chemical
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Inhibition of the norepinephrine transporter function in cultured bovine adrenal medullary cells by ...
Next Document:  Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibr...