Cited by 35Growth Hormone and Insulin-like Growth FactorsProtein Interaction Studies and Fluorescence AnalysisIron Metabolism and Disorders

Transferrin binds insulin‐like growth factors and affects binding properties of insulin‐like growth factor binding protein‐3

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Storch, Stephan, Kübler, Bernd, Höning, Stefan, Ackmann, Michael, Zapf, Jürgen, Blum, Werner, Braulke, Thomas·2001·FEBS Letters

Abstract

In the circulation, most of the insulin‐like growth factors (IGFs) are bound to a ternary 150 kDa complex with IGF‐binding protein (IGFBP)‐3 and the acid labile subunit. In the current study, we identify transferrin (Tf) by mass spectrometry, and immunoprecipitation as a component of a major IGF‐binding fraction separated from human plasma. IGF ligand blotting, cross‐linkage experiments and surface plasmon resonance spectrometry have been used to demonstrate the capability of Tf to bind IGFs specifically. In combination with Tf, IGFBP‐3 showed a 5‐fold higher affinity for IGF‐II than IGFBP‐3 alone. The data suggest that Tf may play an important role in regulating IGF/IGFBP‐3 functions.

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  • Cells derived from FRDA patients contained a 40% increase in mitochondrial iron content and were more susceptible to iron-mediated cytotoxicity and hydrogen peroxide.

    “Similarly, cells derived from FRDA patients contained 40% increase in mitochondrial iron content and were more susceptible to iron-mediated cytotoxicity and hydrogen peroxide (287, 321)”
  • The increased susceptibility of FRDA patient cells to iron-mediated cytotoxicity and hydrogen peroxide was rescued by treatment with deferoxamine or by near-physiologic levels of frataxin expression.

    “which was rescued by treatment with the iron chelator deferoxamine (321) or by near-physiologic levels of frataxin expression (287).”

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  1. Ekblom, P., Thesle¡, I., Saxen, L., Miettinen, A. and Timpl, R. (1983) Proc. Natl. Acad. Sci. USA 80, 2651^2655.

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Authors
Storch, S., Kübler, B., Höning, S., Ackmann, M., Zapf, J., Blum, W., & Braulke, T.
Affiliations
  • Universität Hamburg (DE)
  • University of Göttingen (DE)
  • University Hospital Zurich (CH)
  • Eli Lilly (Germany) (DE)
Corresponding author
Braulke, Thomas
Venue
FEBS Letters
Publisher
Wiley
Published
2001-11-29
Volume
509
Issue
3
Pages
395-398
ISSN
  • 0014-5793 (ISSN-L)
  • 1873-3468
OpenAlex
W1996135852
Cited by
35
References
23
Citations by year
2019: 1 · 2018: 2 · 2017: 2 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 3
FWCI
1.61
Type
journal article
Language
en
Open access
Locations
  • FEBS Letters (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • Deutsche Forschungsgemeinschaft (SFB 402)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
transferrin, insulin-like growth factor, insulin-like growth factor II, IGF binding protein-3, acid-labile subunit, ligand binding affinity, plasma protein binding, growth factor regulation
MeSH terms
Chromatography, Affinity, Chromatography, High Pressure Liquid, Humans, Insulin-Like Growth Factor II, Kinetics, Precipitin Tests, Protein Binding, Mass Spectrometry, Transferrin, Yeasts, Insulin-Like Growth Factor Binding Protein 3, Surface Plasmon Resonance, Two-Hybrid System Techniques

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