Regulation of insulin-like growth factor binding protein-1 expression during aging

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17 Scopus citations


Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is primarily produced in the liver during inflammation and regulates biological activities of IGF-I. Here we demonstrate that interleukin-1β (IL-1β) stimulates IGFBP-1 mRNA production in a dose-dependent manner in hepatocytes from Fisher 344 rats. Employment of c-Jun N-terminal kinase (JNK) inhibitor SP600125 resulted in 3-fold reduction of IGFBP-1 mRNA and protein levels, indicating that IL-1β-induced IGFBP-1 production is mediated through JNK activation. We further show that hepatocytes from aged rats (20-22 mo), as compared to young (3-4 mo), exhibit up to 2-fold higher levels of IGFBP-1 in response to IL-1β. IL-1β-induced phosphorylation of JNK was also significantly higher in aged hepatocytes, and SP600125 treatment eliminated age-related differences in IGFBP-1 mRNA production. Moreover, glutathione depletion in hepatocytes from young rats potently activated JNK, as well as increased IL-1β-induced IGFBP-1 mRNA levels, suggesting that age-related oxidative stress underlies the upregulated JNK activation and IGFBP-1 expression.

Original languageEnglish
Pages (from-to)263-269
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Sep 21 2007

Bibliographical note

Funding Information:
This work was supported by the National Institute of Aging grant RO1 AG019223 (to M.N.N.-K.) and a pre-doctoral fellowship from the American Heart Association (to K.R.). We thank members of Dr. Van Zant’s lab (University of Kentucky) for technical consultations.


  • Glutathione
  • IGFBP-1
  • Inflammation
  • JNK
  • Liver
  • Oxidative stress

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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