Journal article
Distribution of Chimeric IGF Binding Protein (IGFBP)-3 and IGFBP-4 in the Rat Heart: Importance of C-Terminal Basic Region
Endocrinology (Philadelphia), Vol.142(9), pp.3749-3755
09/2001
DOI: 10.1210/endo.142.9.8353
Abstract
Abstract
IGF binding proteins-3 and -4, whether given in the perfused rat heart or given iv in the intact animal, cross the microvascular endothelium of the heart and distribute in subendothelial tissues. IGF binding protein-3, like IGF-I/II, localizes in cardiac muscle, with lesser concentrations in CT elements. In contrast, IGFBP-4 preferentially localizes in CT. In this study, chimeric IGF binding proteins were prepared in which a basic 20-amino-acid C-terminal region of IGF binding protein-3 was switched with the homologous region of IGF binding protein-4, and vice-versa, to create IGF binding protein-34 and IGF binding protein-43. Perfused IGF binding protein-34 behaved like IGF binding protein-4, localizing in connective tissue elements, whereas IGF binding protein-43 now localized in cardiac muscle at concentrations identical to perfused IGF binding protein-3. To determine whether these small mutations altered the affinity of the chimera for cells, the ability of 125I-IGF binding protein-34 and 125I-IGF binding protein-43 to bind to microvascular endothelial cells was determined and compared with IGF binding protein-3. IGF binding protein-34 retained 15% of the binding capacity of IGF binding protein-3, whereas IGF binding protein-43 bound to microvessel endothelial cells with higher affinity and greater total binding than that of IGF binding protein-3. We conclude that small changes in the C-terminal basic domain of IGF binding protein-3 and the corresponding region of IGF binding protein-4 can alter their affinity for cultured cells and influence their tissue distribution in the rat heart.
Details
- Title: Subtitle
- Distribution of Chimeric IGF Binding Protein (IGFBP)-3 and IGFBP-4 in the Rat Heart: Importance of C-Terminal Basic Region
- Creators
- K. L. Knudtson - University of IowaM. Boes - Iowa Diabetes and Endocrinology Research CenterA. Sandra - Iowa Diabetes and Endocrinology Research CenterB. L. Dake - University of IowaB. A. Booth - Iowa Diabetes and Endocrinology Research CenterR. S. Bar - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.142(9), pp.3749-3755
- DOI
- 10.1210/endo.142.9.8353
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Language
- English
- Date published
- 09/2001
- Academic Unit
- Iowa Institute of Human Genetics; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984627287302771
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