Iron-response proteins

Abbreviations IRP (iron responsive protein) ROS (reactive oxygen-derived active species) DP (developed pressure) EDP (end diastolic pressure) WI (cardiac work index) DHBA (dihydroxybenzoic acid) PC preconditioning CFF (coronary flow fraction). 

This communication has reconfirmed the marked protection against myocardial reperfiision injury afforded by ischemic PC. The novel findings in this communication are that following prolonged ischemia, PC causes a marked decrease of the levels of cellular redistribution and extra-cellular mobilization of iron and copper. Furthermore, PC is associated with an accumulation of intracellular ferritin, and a concomitant decrease in ferritin-iron saturation. It is postulated that the low, but significant and reproducible, mobilization levels of intracellular iron, following each cycle of PC, have led to the conversion of the iron-responsive proteins, notably IRP-1, to cytosolic aconitase, and the consequent relief of the tight inhibitory control of ferritin synthesis. 

Iron-response protein (IRP) (83, 84) Translational regulation Sensory... 

The way in which the iron core in ferritin might build up and the structure of the mineral and its properties have been considered by many researchers over the years and yet there are still many questions that remain to be answered satisfactorily. From one viewpoint the subject belongs in the area of biomineralization, from a different standpoint the nanoscale properties have been of interest, and a third important area of research concerns the health aspects of iron storage and homeostasis. For this latter field the problems of too much or too little are to the fore, with iron overload disease a serious problem in much of Africa and the Middle East while in the Western world iron deficiency is more likely to be a problem. A key aspect to such health problems concerns the response of the organism to local iron levels and is regulated in healthy subjects by an iron response element (IRE) which also seems to involve metalloproteins within the so-called iron response protein. However, this has but little bearing on coordination chemistry aspects of ferritins that we are considering here whereas the chemical questions behind the mineralization processes and the measurement and interpretation of the physical properties of such nanoscale particles are of intense interest. It turns out to be helpful to consider these two aspects in tandem, as one tends to inform the other. 

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. 

A major contribution of the free-radical scavenging activity in blood plasma is attributable to the macro-molecular proteins (Wayner et al., 1985) of which albumin is a primary component and trapping agertt (Holt et al., 1984). Serum sulphydryl levels, primarily albumin-related, are decreased in subjects with rheumatoid complicated coalworkers pneumoconiosis, indicative of exacerbated inflammatory R.OM production (Thomas and Evans, 1975). Experimental asbestos inhalation in rats leads to an adaptive but evidendy insufficient response by an increase in endogenous antioxidant enzymes (Janssen etal., 1990). Protection of the vascular endothelium against iron-mediated ROM generation and injury is afforded by the iron sequestiant protein ferritin (Balia et al., 1992). 

Although iron-sulfur proteins are found in various cellular localizations in eukaryotic cells, mitochondria are the major site of Fe-S cluster biosynthesis (Lill et ah, 1999). Deletions in nuclear genes involved in mitochondrial iron-sulfur cluster formation lead to massive accumulation of iron in mitochondria (Chapter 7). For example, deletion of ATM1, a mitochondrial ATPase, which seems to be responsible for the export of Fe-S clusters, leads to respiratory incompetence, excessive iron accumulation and leucine auxotrophy (Kispal et ah, 1999). In Ayfhl cells there is only partial loss of mitochondrial Fe-S enzymes and the cells are not leucine auxotrophs. 

Kennedy, M.C., Mende-Mueller, L., Blondin, G.A., and Beinert, H. 1992. Purification and characterization of cytosolic aconitase from beef hver and its relationship to the iron-responsive element binding protein. Proceedings of the National Academy of Sciences of the USA 89 11730-11734. 

BSA was oxidized by the cupric quercetin complex probably through binding to tryptophan residue [26]. Iwai et al. [27] showed that the iron regulatory protein 2 (IRP2) responsible... 

Rogers, J.T., Randall, J.D., Cahill, C.M., Eder, P.S., et al. (2002) An iron-responsive element type II in the 5 -untranslated region of the Alzheimer s amyloid precursor protein transcript, J. Biol. Chem., 277, 45518-45528. 

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