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Distribution of chimeric IGF binding protein (IGFBP)-3 and IGFBP-4 in the rat heart: importance of C-terminal basic region.

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-3(4) and IGF binding protein-4(3). Perfused IGF binding protein-3(4) behaved like IGF binding protein-4, localizing in connective tissue elements, whereas IGF binding protein-4(3) 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 (125)I-IGF binding protein-3(4) and (125)I-IGF binding protein-4(3) to bind to microvascular endothelial cells was determined and compared with IGF binding protein-3. IGF binding protein-3(4) retained 15% of the binding capacity of IGF binding protein-3, whereas IGF binding protein-4(3) 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.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Knudtson KL,Boes M,Sandra A,Dake BL,Booth BA,Bar RS

doi

10.1210/endo.142.9.8353

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

3749-55

issue

9

eissn

0013-7227

issn

1945-7170

journal_volume

142

pub_type

杂志文章

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