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.
We previously reported that reduction of autocrine IGF-I by polyinosinic-polycytidylic acid [poly(IC)] was permissive for the poly(IC)-mediated decrease in C6 rat glioma cell number. We now report that poly(IC) caused a block in G(1) to S transition in confluent C6 cultures, whereas in subconfluent cultures, poly(IC) decreased the percentage of cells in the G(2)/M phase. Addition of IGF-I to poly(IC)-treated cells decreased the percentage of cells in G(0)/G(1) phase and increased the percentage of cells in G(2)/M phase in confluent and subconfluent C6 cultures, indicating the reversal of cell cycle blocks. Inhibition of protein kinase R (PKR) activation partially prevented the poly(IC)-mediated cytostasis of C6 cells. Poly(IC) induced interferon-alpha in C6 cells. Both IGF-I and a blocking antibody against type I interferon (IFN) prevented the increase in PKR levels and the decrease in cell proliferation caused by poly(IC). We conclude that poly(IC) induces IFN, which mediates the cytostatic effect of poly(IC) on C6 cells at least in part through PKR. IGF-I prevents IFN from inducing PKR, thus explaining the ability of IGF-I to reverse the cell cycle blocks and the decreased C6 proliferation caused by poly(IC).
Chacko
Maryanne S
MS
Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Ma
Xiuye
X
Adamo
Martin L
ML
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004396:Coloring Agents; D004247:DNA / Q000235:genetics; D020536:Enzyme Activators / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D014343:Trypan Blue; D019892:eIF-2 Kinase / Q000378:metabolism*
D004396:Coloring Agents; D020536:Enzyme Activators; D007155:Immunologic Factors; D007370:Interferon Type I; D012330:RNA, Double-Stranded; D007334:Insulin-Like Growth Factor I; D004247:DNA; D019892:eIF-2 Kinase; D014343:Trypan Blue; D011070:Poly I-C; D013936:Thymidine