This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chacko, M. S. Articles by Adamo, M. L. Search for Related Content PubMed PubMed Citation Articles by Chacko, M. S. Articles by Adamo, M. L.

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

Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229-3900

Address all correspondence and requests for reprints to: Martin L. Adamo, Ph.D., Department of Biochemistry, Mail Code 7760, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900. E-mail: adamo{at}biochem.uthscsa.edu

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- 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.

This article has been cited by other articles:

				G. Vitale, P. M. van Koetsveld, W. W. de Herder, K. van der Wansem, J. A. M. J. L. Janssen, A. Colao, G. Lombardi, S. W. J. Lamberts, and L. J. Hofland Effects of type I interferons on IGF-mediated autocrine/paracrine growth of human neuroendocrine tumor cells Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E559 - E566. [Abstract] [Full Text] [PDF]

				V. Hwa, B. Little, E. M. Kofoed, and R. G. Rosenfeld Transcriptional Regulation of Insulin-like Growth Factor-I by Interferon-{gamma} Requires STAT-5b J. Biol. Chem., January 23, 2004; 279(4): 2728 - 2736. [Abstract] [Full Text] [PDF]

				M. S. Chacko, X. Ma, and M. L. Adamo Double-Stranded Ribonucleic Acid Decreases C6 Rat Glioma Cell Proliferation in Part by Activating Protein Kinase R and Decreasing Insulin-Like Growth Factor I Levels Endocrinology, June 1, 2002; 143(6): 2144 - 2154. [Abstract] [Full Text] [PDF]