Double-stranded RNA decreases IGF-I gene expression in a protein kinase R-dependent, but type I interferon-independent, mechanism in C6 rat glioma cells

Maryanne S. Chacko, Martin L Adamo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We previously demonstrated that Poly (IC) decreased the growth of C6 cultures in association with reduced IGF-I synthesis and secretion. In this study we characterized the mechanism(s) by which Poly (IC) decreased IGF-I mRNA in C6 cells. Both Poly (IC) and type I interferon (IFN) decreased IGF-I mRNA. Cycloheximide and a blocking antibody against IFN did not alter the Poly (IC)-mediated inhibition of IGF-I mRNA, but prevented IFN from reducing IGF-I mRNA. Poly (IC) did not alter the stability of IGF-I mRNA. Poly (IC) decreased the abundance of IGF-I pre-mRNA in C6 nuclei, but did not inhibit proximal IGF-I exon 1 promoter/luciferase fusion constructs in transient transfection assays. Poly (IC) activated double-stranded RNA-activated protein kinase (PKR) at 5 min and increased PKR protein levels at 48 and 72 h. Exogenous IGF-I did not prevent Poly (IC) from activating PKR, but inhibited the Poly (IC)-mediated increase in PKR protein levels. The PKR inhibitor 2-aminopurine prevented the Poly (IC) stimulation of eIF2-α phosphorylation and the Poly (IC)-mediated decrease in IGF-I mRNA. We conclude that Poly (IC) decreases IGF-I gene transcription in a mechanism that requires the activation of preexisting PKR, but not the induction of IFN or PKR proteins in C6 cells.

Original languageEnglish (US)
Pages (from-to)525-534
Number of pages10
JournalEndocrinology
Volume143
Issue number2
DOIs
StatePublished - 2002

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Interferon Type I
Double-Stranded RNA
Insulin-Like Growth Factor I
Glioma
Protein Kinases
Gene Expression
Messenger RNA
eIF-2 Kinase
Interferons
2-Aminopurine
Poly I
Proteins
Blocking Antibodies
RNA Precursors
Cycloheximide
Luciferases
Transfection
Exons
Phosphorylation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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Double-stranded RNA decreases IGF-I gene expression in a protein kinase R-dependent, but type I interferon-independent, mechanism in C6 rat glioma cells. / Chacko, Maryanne S.; Adamo, Martin L.

In: Endocrinology, Vol. 143, No. 2, 2002, p. 525-534.

Research output: Contribution to journalArticle

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