Transcriptional Regulation of Ferritin Messenger Ribonucleic Acid Levels by Insulin in Cultured Rat Glioma Cells

Abstract

Recent data have shown that ferritin, a ubiquitous protein, has a role as a regulator of cellular differentiation. In the present study we have investigated the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in response to insulin, which has an important role in cellular growth and differentiation. Insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mRNAs. An increase in the level of ferritin heavy or light chain mRNA was detected after 2 h of incubation with insulin, and a plateau was reached after 48 h for heavy chain mRNA and after 72 h for light chain mRNA. The responses were dose-dependent and were maximal at 100 nM for both mRNAs. Treatment of cells with actinomycin-D showed that insulin had no effect on the posttranscriptional stability of these mRNAs. Actinomycin-D inhibited insulin-induced accumulation of both mRNAs, suggesting transcriptional stimulation of ferritin genes by insulin. A nuclear run-on assay showed that the insulin-induced increase in ferritin heavy chain mRNA was due to an increase in the rate of gene transcription. We also demonstrated that insulin-like growth factor-I (IGF-I) increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion, and that the maximum effect was obtained at a concentration of 10 nM on both mRNA levels. IGF-I was not only 10-fold more potent, but the absolute level of maximum stimulation was also about 2-fold greater than that for insulin. The combination of insulin (100 nM) and IGF-I (10 nM) showed no additive effect. The results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by IGF-I.

Ferritin mRNAs in Schistosoma Mansoni do not have Iron‐Responsive Elements for Post‐Transcriptional Regulation

“…In mammals, ferritin genes are regulated in glioma cells by insulin (Yokomori et al, 1991), in thyroid cells by thyrotropin and C A M P (Chazenbalk et al, 1990), in the pancreatic insulin cells by glucose (MacDonald et al, 1994), in adipocytes and muscle cells by tumor necrosis factor a (Miller et al, 1991), and in monocytes by tumor necrosis factor a and interferon y (Fahmy and Young, 1993). These examples underline the observation that ferritin is regulated at the transcriptional level when it is involved in differentiation or developmental processes (Theil, 1990b).…”

Circulating soluble transferrin receptor concentration decreases after exercise-induced improvement of insulin sensitivity in obese individuals

“…Iron circulates in a form bound to transferrin and is taken up from the blood by a high-affinity specific transferrin receptor (TfR). [1][2][3] Insulin is known to cause a rapid and marked stimulation of iron uptake by different cell types, redistributing TfRs from an intracellular membrane compartment to the cell surface. [1][2][3] Iron uptake by insulin parallels its effects on glucose transport.…”

“…[1][2][3] Insulin is known to cause a rapid and marked stimulation of iron uptake by different cell types, redistributing TfRs from an intracellular membrane compartment to the cell surface. [1][2][3] Iron uptake by insulin parallels its effects on glucose transport. 4 As a result of the externalization of TfR during the endocytic cycle, a soluble form of TfR (sTfR) can be detected in serum.…”

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“…TNFa regulation of FTH1 is through its binding to the p50 and p65 subunits of NFκB [73]. In addition, expression of FTH1 appears to be regulated by insulin, IGF-1 and thyroid hormone [74,75]. Cytokines also regulate the post-transcriptional modification of ferritin possibly through their ability to induce iNOS [74,75].…”

“…In addition, expression of FTH1 appears to be regulated by insulin, IGF-1 and thyroid hormone [74,75]. Cytokines also regulate the post-transcriptional modification of ferritin possibly through their ability to induce iNOS [74,75]. As noted by Torti & Torti [70], the pathways that link ferritin gene expression with cell stress and altered growth regulation are just beginning to be explored and based on present knowledge are very complex and multifaceted.…”