Ferritin expression

The existence of an iron-responsive cis-acting element in plant ferritin genes has been indicated in a series of studies. For example, iron-dependent induction of ferritin synthesis coincided with increased transcription and accumulation of ferritin mRNA [3]. Moreover, insertion of the animal IRE (mRNA iron responsive element) into soybean ferritin mRNA did not have much effect on the translation of the mRNA [4]. In addition, regulation of soybean ferritin expression in nodules [5] appeared to be posttranslational [6]. Finally, no IRE sequence was found in ferritin gene sequences from either maize or soybeans [7]. In fact, the organization of plant... 

Exposure of 1X10 human alveolar macrophages to 100 [ig silica/ml for 4 h increased ferritin protein concentrations by approximately 50 % of the baseline value in both supernatants and lysates (Ghio et al. 1997). Inclusion of 1.0 mM deferoxamine, an iron chelator, in the reaction mixtures inhibited increases after silica. There were no increases in ferritin after incubation with acid-washed particles or silica with complexed zinc cation. There were no significant differences in levels of ferritin cDNA between any of the exposures suggesting a post-transcriptional control of ferritin expression. 

For our model system, hepatic ferritin gene expression was monitored in response to interleukin-1 (IL-1) [71]. IL-1 was found to significantly increase ferritin translation by signaling though a novel translation enhancer element, the acute box motif, downstream from the IREs at the 5 cap site [45, 72]. This acute box motif is located immediately downstream from Iron-responsive Element in the 5 untranslated regions of both the L- and H-ferritin transcripts [73], and was also found to be present in front of the start codon in the APP transcript [47]. This observation was consistent with the pattern of both APP and ferritin expression in response to inflammation during both Alzheimer s disease and the anemia associated with chronic disease. 

Ferritin expression is regulated through a posttranscriptional mechanism (114-120). A specific sequence at the 5 -untranslated end of ferritin mRNA,... 

Kobune M, Kohgo Y, Kato J, Miyazaki E, Niitsu Y. Interleukin-6 enhances hepatic transferrin uptake and ferritin expression in rats. Hepatology 1994 19 1468-1475. 

Synthesis of the transferrin receptor (TfR) and that of ferritin are reciprocally linked to cellular iron content. Specific untranslated sequences of the mRNAs for both proteins (named iron response elements) interact with a cytosolic protein sensitive to variations in levels of cellular iron (iron-responsive element-binding protein). When iron levels are high, cells use stored ferritin mRNA to synthesize ferritin, and the TfR mRNA is degraded. In contrast, when iron levels are low, the TfR mRNA is stabilized and increased synthesis of receptors occurs, while ferritin mRNA is apparently stored in an inactive form. This is an important example of control of expression of proteins at the translational level. 

In 1976, Hamish Munro proposed a model for the translational control of ferritin synthesis (Zahringer et al., 1976), which not only represents a crucial and remarkably far-sighted contribution to our understanding of cellular iron metabolism, but also in the more general context of the posttranscriptional control of gene expression. 

Fig. 14. Magnetization curves of reconstituted horse spleen ferritin. The solid lines are fits to expression (14). Reproduced with permission from Ref (35).

The expression of several genes is induced or repressed by hemopexin-mediated heme transport. Most of these are simple responses of the cell to the increased heme (or iron derived from heme) in the cell. For example, HO-1 is induced (15, 88), ferritin levels rise (14, 61, 89), the transferrin receptor is down-regulated (15), and hemopexin mRNA itself is induced (A. Smith, unpublished). However, MT-1 is also induced, apparently to prepare the cell for oxidative stress thus, in addition to sequestering heme in a low-spin, non-oxidatively active form, hemopexin also indirectly exerts antioxidant effects by inducing MT-1 (16, 61, 90). 

Variations in ferritin protein coats coincide with variations in iron metabolism and gene expression, suggesting an Interdependence. Iron core formation from protein coats requires Fe(Il), at least experimentally, which follows a complex path of oxidation and hydrolytic polymerization the roles of the protein and the electron acceptor are only partly understood. It is known that mononuclear and small polynuclear Fe clusters bind to the protein early in core formation. However, variability in the stoichiometry of Fe/oxidant and the apparent sequestration and stabilization of Fe(II) in the protein for long periods of time indicate a complex microenvironment maintained by the protein coats. Full understanding of the relation of the protein to core formation, particularly at intermediate stages, requires a systematic analysis using defined or engineered protein coats. 

The down-regulated proteins in HCC tissues have been identified. Park et al. identified aldehyde dehydrogenase 2 (25) and ferritin light chain (32). Kim et al. identified HSP 27, cathepsin D, and others (26). Lim et al. identified cytochrome B5, liver car-boxyesterase, and others (27). Li et al. identified SOD 1, aldolase B, and others (28). Fujii et al. identified galectin-1 (29). Kim et al. identified argininosuccinate synthase, carbamoyl-phosphate s mthase, and others (31). Table 1 shows the summary of the proteins whose expression was different between HCC cancer tissues and non-cancerous tissues. 

Table 3 shows the proteins up-regulated or down-regulated in panereatie eaneer tissues. Shen et al. reported that, in panereatie eaneer tissues, expressions of Mn-SOD, S100A8, annexin A4, eathepsin D, 14-3-3 zeta, tropomyosin 2, aetin, ferritin light chain, alpha-enolase, galectin-1, and cyclophilin A increased, and that those of peroxiredoxin... 

A dipeptide Met- , derived from sardine muscle (Matsufuji et ah, 1994), stimulates expression of the antioxidant defense protein HO-1 in a concentration-dependent manner. Previous findings revealed that HO-1 protein expression is accompanied by the induction of a secondary antioxidant protein, ferritin. In a present study, the effect of Met- on the expression of the antioxidant stress proteins, heme oxygenase-1 (HO-1), and ferritin in endothelial cells derived from the human umbilical vein and their contribution to the decrease in radical formation that occurs under the influence of this dipeptide were studied and reported potential activity (Erdmann et ah, 2006). 

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